Development and Structure of The Human Reproductive System
Assigned females at birth are considered the “fundamental” sex—that is, without
much chemical prompting, all fertilized eggs would develop into assigned females at
birth. To be assigned male at birth, an individual must be exposed to the cascade of
factors initiated by a single gene on the male Y chromosome. This is called the SRY
(Sex-determining Region of the Y chromosome). Because females assigned at birth
do not have a Y chromosome, they do not have the SRY gene. Without a functional
SRY gene, an individual will be assigned female at birth. In all embryos, the same
group of cells has the potential to develop into the primordial sex specific gonads; this
tissue is considered bipotential. The SRY gene actively recruits other genes that begin
to develop the testes, and suppresses genes that are important in anatomical female
development. As part of this SRY-prompted cascade, germ cells in the bipotential
gonads differentiate into spermatogonia. Without SRY, different genes are expressed,
oogonia form, and primordial follicles develop in the primitive ovary. Soon after the
formation of the testes, the Leydig cells begin to secrete testosterone. Testosterone
can influence tissues that are bipotential to become male assigned at birth
reproductive structures. For example, with exposure to testosterone, cells that could
become either the glans penis or the glans clitoris form the glans penis. Without
testosterone, these same cells differentiate into the clitoris. Not all tissues in the
reproductive tract are bipotential. The internal reproductive structures (for example the
uterus, fallopian tubes, and part of the vagina in people assigned female at birth; and
the epididymis, ductus deferens, and seminal vesicles in people assigned male at birth
form from one of two rudimentary duct systems in the embryo.
From a medical perspective, differentiated sex development or DSD can occur
in approximately 1 in 100 individuals. The general term for people born with DSD is
Intersex. This umbrella term is used for a range of variations that can occur when a
person does not have the specific anatomy or chromosomal markers that would
typically assign them either male or female. This is roughly the same statistical
variation for green eyes or red hair factoring in a margin of error of 2%. According to
our current understanding there are approximately twenty-five genes that have an
impact on anatomical sex development. Taken together as an umbrella category, an
estimated forty types of DSD have been medically recorded with approximately eight
of those being the typical determinants of DSD across a normalized population
sample.
As with most complex systems including biological organisms, simple models are
often necessary to provide a shortcut to understanding. However, the risk in using
these models is that they lack nuance and they rarely show the larger picture in context
to other connected systems. Looping back to the spectra of medical sex, most
secondary and primary school textbooks as well as some introductory level college
texts use a simplified XX/XY model to demonstrate reproductive characteristics within
a lifecycle. The XX/XY model is incomplete and lacks a large amount of understanding
in how all the biological systems reflect and inform one another. Models and shortcuts
are useful; for example, this work has used the term ‘assigned sex’ here to differentiate
itself from sex as a larger psycho-social categorization but even that lacks nuance to
a medical clinician since ‘assigned sex’ can be further broken down into chromosomal,
gonadal or anatomical specialties as well as how hormones impact primary and
secondary sex characteristics. These differentiations are particularly important in
healthcare decisions as these specialties might be in completely different hospital
departments.
As new data and training is filtered down slowly through the medical
establishment, medical sex is now thought of to be closer to polygenetic traits since it
results in a variety of expressions. Consider that it is not, nor has it ever been a strictly
binary category. This chapter focuses primarily on human anatomy but it is important
to understand that as humans we are much more than our body parts. As we unpack
the intersectionality of self throughout the course of this textbook we will come back to
shed more light on the Intersex community. The link below is a good place to start.
Intersex Community Q&A Series – YouTube.
Puberty is the stage of development at which individuals become sexually
mature. Though the outcomes of puberty significantly differ depending on assigned
sex at birth, the hormonal control of the process is very similar. In addition, though the
timing of these events varies between individuals, the sequence of changes that occur
is fairly predictable for adolescents. As shown in Figure 27.18, a concerted release of
hormones from the hypothalamus gonadotropin-releasing hormone (GnRH), the
anterior pituitary-luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and
the gonads (either testosterone or estrogen) is responsible for the maturation of the
reproductive systems and the development of secondary sex characteristics, which
are physical changes that serve auxiliary roles in reproduction.
In addition to age, multiple factors can affect the age of onset of puberty, including
genetics, environment, and psychological stress. One of the more important influences
may be nutrition; historical data demonstrate the effect of better and more consistent
nutrition on the age of menarche, (first menstruation) in the United States, which
decreased from an average age of approximately 17 years of age in 1860 to the
current age of approximately 12.75 years in 1960, as it remains today. Some studies
indicate a link between puberty onset and the amount of stored fat in an individual.
This effect is more pronounced in people assigned female at birth, but has also been
documented in people assigned male at birth. Body fat, corresponding with secretion
of the hormone leptin by adipose cells, appears to have a strong role in determining
menarche. This may reflect to some extent the high metabolic costs of gestation and
lactation.
Different sex steroid hormone concentrations between the sexes also contribute
to the development and function of secondary sexual characteristics. As assigned
females at birth reach puberty, typically the first change that is visible is the
development of the breast tissue. This is followed by the growth of axillary and pubic
hair. A growth spurt normally starts at approximately age 9 to 11, and may last two
years or more. During this time, their height can increase 3 inches a year. The next
step in puberty is menarche, the start of menstruation.
For assigned males at birth, the growth of the testes is typically the first physical
sign of the beginning of puberty, which is followed by growth and pigmentation of the
scrotum and growth of the penis. The next step is the growth of hair, including armpit,
pubic, chest, and facial hair. Testosterone stimulates the growth of the larynx and
thickening and lengthening of the vocal folds, which causes the voice to drop in pitch.
The first fertile ejaculations typically appear at approximately 15 years of age, but this
age can vary widely. Unlike the early growth spurt observed in assigned females,
assigned male’s growth spurts occur toward the end of puberty, at approximately age
16 to 18, and their height can increase as much as 4 inches a year. In some, pubertal
development can continue through the early 20s.
Human reproductive systems begin to develop soon after conception. A gene on
the assigned male’s Y chromosome is called SRY. SRY is critical in stimulating a
cascade of events that simultaneously stimulate testis development and repress the
development of assigned female structures. Testosterone produced by Leydig cells in
the embryonic testis stimulates the development of assigned male sexual organs. If
testosterone is not present, female sexual organs will develop. Whereas the gonads
and some other reproductive tissues are considered bipotential, the tissue that forms
the internal reproductive structures stems from ducts that will develop into only
assigned male (Wolffian) or assigned female (Müllerian) structures. To be able to
reproduce as an adult, one of these systems must develop properly and the other must
degrade.
Further development of the reproductive systems occurs at puberty. The initiation
of the changes that occur in puberty is the result of a decrease in sensitivity to negative
feedback in the hypothalamus and pituitary gland, and an increase in sensitivity of the
gonads to FSH and LH stimulation. These changes lead to increases in either estrogen
or testosterone, in assigned female and male adolescents, respectively. The increase
in sex steroid hormones leads to maturation of the gonads and other reproductive
organs. The initiation of spermatogenesis begins in assigned males, and assigned
females begin ovulating and menstruating. Increases in sex steroid hormones also
lead to the development of secondary sex characteristics, such as breast development
in assigned females and facial hair and larynx growth in assigned males. The previous
section highlights the ways in which fetal sexual anatomical formation occurs. It covers
both the dymorphism associated with those assigned female at birth, those assigned
male at birth and includes intersex anatomical formation which is varied in type.
Human sexual reproduction involves the fertilization of an ovum by a sperm, the
remaining portion of this chapter will be divided, in order to explore anatomical systems
within bodies assigned female at birth and bodies assigned male at birth.
The external-assigned female reproductive structures are referred to collectively
as the vulva. The mons pubis is a pad of fat that is located at the anterior, over the
pubic bone. After puberty, it becomes covered in pubic hair. The labia majora (labia =
“lips”; majora = “larger”) are folds of hair-covered skin that begin just posterior to the
mons pubis. The thinner and more pigmented labia minora (labia = “lips”; minora =
“smaller”) extend medially to the labia majora. External genitalia naturally vary in
shape and size; the labia minora serve to protect the urethra and the entrance to the
reproductive tract.
The superior, anterior portions of the labia minora come together to encircle the
clitoris (or glans clitoris), an organ that originates from the same cells as the glans
penis and has abundant nerves, which make it important in sexual sensation and
orgasm. The hymen is a thin membrane that sometimes partially covers the entrance
to the vagina. An intact hymen cannot be used as an indication of “virginity;” even at
birth, this is only a partial membrane, as menstrual fluid and other secretions must be
able to exit the body, regardless of vaginal intercourse. The vaginal opening is located
between the opening of the urethra and the anus. It is flanked by outlets to the
Bartholin’s glands (or greater vestibular glands).
The vagina is a muscular canal (approximately 10 cm long) that serves as the
entrance to the reproductive tract. It also serves as the exit from the uterus during
menses and childbirth. The outer walls of the anterior and posterior vagina are formed
into longitudinal columns, or ridges, and the superior portion of the vagina—called the
fornix—meets the protruding uterine cervix. The walls of the vagina are lined with an
outer, fibrous adventitia, a middle layer of smooth muscle, and an inner mucous
membrane with transverse folds called rugae. Together, the middle and inner layers
allow the expansion of the vagina to accommodate intercourse and childbirth. The thin,
perforated hymen can partially surround the opening to the vaginal orifice. The
Bartholin’s glands and the lesser vestibular glands (located near the clitoris) secrete
mucus, which keeps the vestibular area moist. The vagina is home to a normal
population of microorganisms that help to protect against infection by pathogenic
bacteria, yeast, or other organisms that can enter the vagina. In a healthy vagina, the
most predominant type of vaginal bacteria is from the genus Lactobacillus. This family
of beneficial bacterial flora secretes lactic acid, and thus protects the vagina by
maintaining an acidic pH (below 4.5). Potential pathogens are less likely to survive in
these acidic conditions. Lactic acid, in combination with other vaginal secretions,
makes the vagina a self-cleansing organ.
The ovaries are the female gonads. Paired ovals, they are each about 2 to 3 cm
in length, about the size of an almond. The ovaries are located within the pelvic cavity,
and are supported by the mesovarium, an extension of the peritoneum that connects
the ovaries to the broad ligament. Extending from the mesovarium itself is the
suspensory ligament, which contains the ovarian blood and lymph vessels. Finally, the
ovary itself is attached to the uterus via the ovarian ligament. The ovary comprises an
outer covering of cuboidal epithelium called the ovarian surface epithelium that is
superficial to a dense connective tissue covering called the tunica albuginea. Beneath
the tunica albuginea is the cortex, or outer portion, of the organ. The cortex is
composed of a tissue framework called the ovarian stroma that forms the bulk of the
adult ovary. Oocytes develop within the outer layer of this stroma, each surrounded by
supporting cells. This grouping of an oocyte and its supporting cells is called a follicle.
Beneath the cortex lies the inner ovarian medulla, the site of blood vessels, lymph
vessels, and the nerves of the ovary.
The ovarian cycle is a set of predictable changes in the majority of assigned
female’s oocytes and ovarian follicles. During an assigned female’s reproductive
years, it is a roughly 28-day cycle that can be correlated with, but is not the same as,
the menstrual cycle (discussed shortly). The cycle includes two interrelated processes:
oogenesis (the production of female gametes) and folliculogenesis (the growth and
development of ovarian follicles).
Gametogenesis in females is called oogenesis. The process begins with the
ovarian stem cells, or oogonia. Oogonia are formed during fetal development, and
divide via mitosis, much like spermatogonia in the testis. Unlike spermatogonia,
however, oogonia form primary oocytes in the fetal ovary prior to birth. These primary
oocytes are then arrested in this stage of meiosis I, only to resume it years later,
beginning at puberty and continuing until the start of menopause (the cessation of
reproductive functions). The number of primary oocytes present in the ovaries declines
from one million to two million in an infant, to approximately 400,000 at puberty, to zero
by the end of menopause.
The initiation of ovulation—the release of an oocyte from the ovary—marks the
transition from puberty into reproductive maturity. From then on, throughout
reproductive years, ovulation occurs approximately once every 28 days. Just prior to
ovulation, a surge of luteinizing hormone triggers the resumption of meiosis in a
primary oocyte. This initiates the transition from primary to secondary oocyte.
However, as you can see, this cell division does not result in two identical cells.
Instead, the cytoplasm is divided unequally, and one daughter cell is much larger than
the other. This larger cell, the secondary oocyte, eventually leaves the ovary during
ovulation. The smaller cell, called the first polar body, may or may not complete
meiosis and produce second polar bodies; in either case, it eventually disintegrates.
Therefore, even though oogenesis produces up to four cells, only one survives.
The unequal cell division of oogenesis produces one to three polar bodies that
later degrade, as well as a single haploid ovum, which is produced only if there is
penetration of the secondary oocyte by a sperm cell. How does the diploid secondary
oocyte become an ovum—the haploid assigned female gamete? Meiosis of a
secondary oocyte is completed only if a sperm succeeds in penetrating its barriers.
Meiosis II then resumes, producing one haploid ovum that, at the instant of fertilization
by a (haploid) sperm, becomes the first diploid cell of the new offspring (a zygote).
Thus, the ovum can be thought of as a brief, transitional, haploid stage between the
diploid oocyte and diploid zygote.
The larger amount of cytoplasm contained in the assigned female gamete is used
to supply the developing zygote with nutrients during the period between fertilization
and implantation into the uterus. Interestingly, sperm contribute only DNA at
fertilization —not cytoplasm. Therefore, the cytoplasm and all of the cytoplasmic
organelles in the developing embryo are of maternal origin. This includes
mitochondria, which contain their own DNA. Scientific research in the 1980s
determined that mitochondrial DNA was maternally inherited, meaning that you can
trace your mitochondrial DNA directly to your birth mother, their birth mother, and so
on back through your matrilineal ancestors.
Ovarian follicles are oocytes and their supporting cells. They grow and develop
in a process called folliculogenesis, which typically leads to ovulation of one follicle
approximately every 28 days, along with death to multiple other follicles. The death of
ovarian follicles is called Atresia, and can occur at any point during follicular
development. Recall that, assigned female infants at birth will have one million to two
million oocytes within their ovarian follicles, and that this number declines throughout
life until menopause, when no follicles remain. Follicles progress from primordial, to
primary, to secondary and tertiary stages prior to ovulation—with the oocyte inside the
follicle remaining as a primary oocyte until right before ovulation. Folliculogenesis
begins with follicles in a resting state. These small primordial follicles are present in
newborns and are the prevailing follicle type in the adult ovary (Figure). Primordial
follicles have only a single flat layer of support cells, called granulosa cells, that
surround the oocyte, and they can stay in this resting state for years—some until right
before menopause. Keep in mind that most follicles don’t grow and develop until
ovulation. In fact, roughly 99 percent of the follicles in the ovary will undergo atresia
(they die), which can occur at any stage of folliculogenesis.
The process of development that we have just described, from primordial follicle
to early tertiary follicle, takes approximately two months in humans. The final stages
of development of a small cohort of tertiary follicles, ending with ovulation of a
secondary oocyte, occur over a course of approximately 28 days. These changes in
the reproductive system are regulated by hormones including gonadotropinreleasing
hormone (GnRH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
The hypothalamus produces GnRH, a hormone that signals the anterior pituitary
gland to produce the gonadotropins FSH and LH (Figure). These gonadotropins leave
the pituitary and travel through the bloodstream to the ovaries, where they bind to
receptors on the granulosa and theca cells of the follicles. FSH stimulates the follicles
to grow (hence its name of follicle-stimulating hormone), and the five or six tertiary
follicles expand in diameter. The release of LH also stimulates the granulosa and theca
cells of the follicles to produce the sex steroid hormone estradiol, a type of estrogen.
This phase of the ovarian cycle, when the tertiary follicles are growing and secreting
estrogen, is known as the follicular phase. The more granulosa and theca cells a
follicle has (that is, the larger and more developed it is), the more estrogen it will
produce in response to LH stimulation. As a result of these large follicles producing
large amounts of estrogen, systemic plasma estrogen concentrations increase.
Following a classic negative feedback loop, the high concentrations of estrogen will
stimulate the hypothalamus and pituitary to reduce the production of GnRH, LH, and
FSH. Because the large tertiary follicles require FSH to grow and survive at this point,
this decline in FSH caused by negative feedback leads most of them to die (atresia).
Typically only one follicle, now called the dominant follicle, will survive this reduction
in FSH, and this follicle will be the one that releases an oocyte.
The hypothalamus and pituitary gland regulate the ovarian cycle and ovulation.
GnRH activates the anterior pituitary to produce LH and FSH, which stimulate the
production of estrogen and progesterone by the ovaries. When only the one dominant
follicle remains in the ovary, it again begins to secrete estrogen. It produces more
estrogen than all of the developing follicles did together before the negative feedback
occurred. It produces so much estrogen that the normal negative feedback doesn’t
occur. Instead, these extremely high concentrations of systemic plasma estrogen
trigger a regulatory switch in the anterior pituitary that responds by secreting large
amounts of LH and FSH into the bloodstream (see Figure). The positive feedback loop
by which more estrogen triggers release of more LH and FSH only occurs at this point
in the cycle.
It is this large burst of LH (called the LH surge) that leads to ovulation of the
dominant follicle. The LH surge induces many changes in the dominant follicle,
including stimulating the resumption of meiosis of the primary oocyte to a secondary
oocyte. As noted earlier, the polar body that results from unequal cell division simply
degrades. The LH surge also triggers proteases (enzymes that cleave proteins) to
break down structural proteins in the ovary wall on the surface of the bulging dominant
follicle. This degradation of the wall, combined with pressure from the large, fluid-filled
antrum, results in the expulsion of the oocyte surrounded by granulosa cells into the
peritoneal cavity. This release is ovulation.
The Fallopian Tubes (also called uterine tubes or oviducts) serve as the conduit
of the oocyte from the ovary to the uterus (Figure). Each of the two fallopian tubes is
close to, but not directly connected to, the ovary and divided into sections. The isthmus
is the narrow medial end of each uterine tube that is connected to the uterus. The wide
distal infundibulum flares out with slender, finger-like projections called fimbriae. The
middle region of the tube, called the ampulla, is where fertilization often occurs. The
fallopian tubes also have three layers: an outer serosa, a middle smooth muscle layer,
and an inner mucosal layer. In addition to its mucus-secreting cells, the inner mucosa
contains ciliated cells (covered in microscopic projections that look like tiny hairs) that
beat in the direction of the uterus, producing a current that will be critical to move the
oocyte. Following ovulation, the secondary oocyte surrounded by a few granulosa cells
is released into the peritoneal cavity. The nearby uterine tube, either left or right,
receives the oocyte. Unlike sperm, oocytes lack flagella (microscopic appendage that
allows sperm to swim), and therefore cannot move on their own. So how do they travel
into the uterine tube and toward the uterus? High concentrations of estrogen that occur
around the time of ovulation induce contractions of the smooth muscle along the length
of the uterine tube. These contractions occur every 4 to 8 seconds, and the result is a
coordinated movement that sweeps the surface of the ovary and the pelvic cavity
(some women can feel those contractions called Middleschmertz- meaning “middle
pain” in German). Current flowing toward the uterus is generated by coordinated
beating of the cilia that line the outside and lumen of the length of the uterine tube.
These cilia beat more strongly in response to the high estrogen concentrations that
occur around the time of ovulation. As a result of these mechanisms, the oocyte–
granulosa cell complex is pulled into the interior of the tube. Once inside, the muscular
contractions and beating cilia move the oocyte slowly toward the uterus. When
fertilization does occur, sperm typically meet the ovum while it is still moving through
the ampulla.
The uterus is the muscular organ that nourishes and supports the growing
embryo. Its average size is approximately 5 cm wide by 7 cm long (approximately 2 in
by 3 in) in a non-pregnant state. It has three sections. The portion of the uterus superior
to the opening of the uterine tubes is called the fundus. The middle section of the
uterus is called the body of the uterus (or corpus). The cervix is the narrow inferior
portion of the uterus that projects into the vagina. The cervix produces mucus
secretions that become thin and stringy under the influence of high systemic plasma
estrogen concentrations, and these secretions can facilitate sperm movement through
the reproductive tract. Several ligaments maintain the position of the uterus within the
abdominopelvic cavity. The broad ligament is a fold of peritoneum that serves as a
primary support for the uterus, extending laterally from both sides of the uterus and
attaching it to the pelvic wall. The round ligament attaches to the uterus near the
uterine tubes, and extends to the labia majora. Finally, the uterosacral ligament
stabilizes the uterus posteriorly, by its connection from the cervix to the pelvic wall.
The wall of the uterus is made up of three layers. The most superficial layer is the
serous membrane, or perimetrium, which consists of epithelial tissue that covers the
exterior portion of the uterus. The middle layer, or myometrium, is a thick layer of
smooth muscle responsible for uterine contractions. Most of the uterus is myometrial
tissue, and the muscle fibers run horizontally, vertically, and diagonally, allowing the
powerful contractions that occur during labor and the less powerful contractions (or
cramps) that help to expel blood during menstruation. Anteriorly directed myometrial
contractions also occur near the time of ovulation, and are thought to possibly facilitate
the transport of sperm through the female reproductive tract.
The innermost layer of the uterus is called the endometrium. The endometrium
contains a connective tissue lining, the lamina propria, which is covered by epithelial
tissue that lines the lumen. Structurally, the endometrium consists of two layers: the
stratum basalis and the stratum functionalis (the basal and functional layers). The
stratum basalis layer is part of the lamina propria and is adjacent to the myometrium;
this layer does not shed during menses. In contrast, the thicker stratum functionalis
layer contains the glandular portion of the lamina propria and the endothelial tissue
that lines the uterine lumen. It is the stratum functionalis that grows and thickens in
response to increased levels of estrogen and progesterone. In the luteal phase of the
menstrual cycle, special branches of the uterine artery, called spiral arteries, supply
the thickened stratum functionalis. This inner functional layer provides the proper site
of implantation for the fertilized ovum, and—should fertilization not occur—it is only
the stratum functionalis layer of the endometrium that sheds during menstruation.
Recall that during the follicular phase of the ovarian cycle, the tertiary follicles are
growing and secreting estrogen. At the same time, the stratum functionalis of the
endometrium is thickening to prepare for a potential implantation. The postovulatory
increase in progesterone, which characterizes the luteal phase, is key for maintaining
a thick stratum functionalis. As long as a functional corpus luteum is present in the
ovary, the endometrial lining is prepared for implantation. Indeed, if an embryo
implants, signals are sent to the corpus luteum to continue secreting progesterone to
maintain the endometrium, and thus maintain the pregnancy. If an embryo does not
implant, no signal is sent to the corpus luteum and it degrades, ceasing progesterone
production and ending the luteal phase. Without progesterone, the endometrium thins
and, under the influence of prostaglandins, the spiral arteries of the endometrium
constrict and rupture, preventing oxygenated blood from reaching the endometrial
tissue. As a result, endometrial tissue dies and blood, pieces of the endometrial tissue,
and white blood cells are shed through the vagina during menstruation, or the menses.
The first menses after puberty, called menarche, can occur either before or after the
first ovulation.
Now that we have discussed the maturation of the cohort of tertiary follicles in
the ovary, the build-up and then shedding of the endometrial lining in the uterus, and
the function of the uterine tubes and vagina, we can put everything together to talk
about the three phases of the menstrual cycle—the series of changes in which the
uterine lining is shed, rebuilds, and prepares for implantation. The timing of the
menstrual cycle starts with the first day of menses. Cycle length is determined by
counting the days between the onset of bleeding in two subsequent cycles. Because
the average length of a menstrual cycle is 28 days, this is the time period used to
identify the timing of events in the cycle. However, the length of the menstrual cycle
varies among individuals, and even in the same person from one cycle to the next,
typically from 21 to 32 days. Just as the hormones produced by the granulosa and
theca cells of the ovary “drive” the follicular and luteal phases of the ovarian cycle,
they also control the three distinct phases of the menstrual cycle. These phases are
the menses phase, the proliferative phase, and the secretory phase.
The menses phase of the menstrual cycle is the phase during which the lining is
shed; that is, the days a person menstruates. Although it averages approximately five
days, the menses phase can last from 2 to 7 days, or longer. As shown in Figure, the
menses phase occurs during the early days of the follicular phase of the ovarian cycle,
when progesterone, FSH, and LH levels are low.
Once menstrual flow ceases, the endometrium begins to proliferate again,
marking the beginning of the proliferative phase of the menstrual cycle. It occurs when
the granulosa and theca cells of the tertiary follicles begin to produce increased
amounts of estrogen. These rising estrogen concentrations stimulate the endometrial
lining to rebuild. The switch to positive feedback—which occurs with the elevated
estrogen production from the dominant follicle—then stimulates the LH surge that will
trigger ovulation. In a typical 28-day menstrual cycle, ovulation occurs on day 14.
Ovulation marks the end of the proliferative phase as well as the end of the follicular
phase.
In addition to prompting the LH surge, high estrogen levels increase the uterine
tube contractions that facilitate the pick-up and transfer of the ovulated oocyte. High
estrogen levels also slightly decrease the acidity of the vagina, making it more
hospitable to sperm. In the ovary, the luteinization of the granulosa cells of the
collapsed follicle forms the progesterone-producing corpus luteum, marking the
beginning of the luteal phase of the ovarian cycle. In the uterus, progesterone from the
corpus luteum begins the secretory phase of the menstrual cycle, in which the
endometrial lining prepares for implantation (see Figure). Over the next 10 to 12 days,
the endometrial glands secrete a fluid rich in glycogen. If fertilization has occurred, this
fluid will nourish the ball of cells now developing from the zygote. At the same time,
the spiral arteries develop to provide blood to the thickened stratum functionalis. If no
pregnancy occurs within approximately 10 to 12 days, the corpus luteum will degrade
into the corpus albicans. Levels of both estrogen and progesterone will fall, and the
endometrium will grow thinner. Prostaglandins will be secreted that cause constriction
of the spiral arteries, reducing oxygen supply. The endometrial tissue will die, resulting
in menses—or the first day of the next cycle.
Whereas the breasts are located far from the other reproductive organs, they are
considered accessory organs of the reproductive system. The function of the breasts
is to supply milk to an infant in a process called lactation. The external features of the
breast include a nipple surrounded by a pigmented areola (Figure), whose coloration
may deepen during pregnancy. The areola is typically circular and can vary in size
from 25 to 100 mm in diameter. The areolar region is characterized by small, raised
areolar glands that secrete lubricating fluid during lactation to protect the nipple from
chafing. When a baby nurses, or draws milk from the breast, the entire areolar region
is taken into the mouth.
Breast milk is produced by the mammary glands, which are modified sweat
glands. The milk itself exits the breast through the nipple via 15 to 20 lactiferous ducts
that open on the surface of the nipple. These lactiferous ducts each extend to a
lactiferous sinus that connects to a glandular lobe within the breast itself that contains
groups of milk-secreting cells in clusters called alveoli (see Figure). The clusters can
change in size depending on the amount of milk in the alveolar lumen. Once milk is
made in the alveoli, stimulated myoepithelial cells that surround the alveoli contract to
push the milk to the lactiferous sinuses. From here, the baby can draw milk through
the lactiferous ducts by suckling. The lobes themselves are surrounded by fat tissue,
which determines the size of the breast; breast size differs between individuals and
does not affect the amount of milk produced. Supporting the breasts are multiple bands
of connective tissue called suspensory ligaments, which connect the breast tissue to
the dermis of the overlying skin.
During lactation, milk moves from the alveoli through the lactiferous ducts to the
nipple. During the hormonal fluctuations in the menstrual cycle, breast tissue responds
to changing levels of estrogen and progesterone, which can lead to swelling and
breast tenderness in some individuals, especially during the secretory phase. If
pregnancy occurs, the increase in hormones leads to further development of the
mammary tissue and enlargement of the breasts.
The external genitalia are collectively called the vulva. The vagina is the pathway
into and out of the uterus. A penis is inserted into the vagina to deliver sperm, and the
baby exits the uterus through the vagina during childbirth. The ovaries produce
oocytes, the female gametes, in a process called oogenesis. As with spermatogenesis,
meiosis produces the haploid gamete (in this case, an ovum); however, it is completed
only in an oocyte that has been penetrated by a sperm. In the ovary, an oocyte
surrounded by supporting cells is called a follicle. In folliculogenesis, primordial follicles
develop into primary, secondary, and tertiary follicles. Early tertiary follicles with their
fluid-filled antrum will be stimulated by an increase in FSH, a gonadotropin produced
by the anterior pituitary, to grow in the 28-day ovarian cycle. Supporting granulosa and
theca cells in the growing follicles produce estrogens, until the level of estrogen in the
bloodstream is high enough that it triggers negative feedback at the hypothalamus and
pituitary. This results in a reduction of FSH and LH, and most tertiary follicles in the
ovary undergo atresia (they die). One follicle, usually the one with the most FSH
receptors, survives this period and is now called the dominant follicle. The dominant
follicle produces more estrogen, triggering positive feedback and the LH surge that will
induce ovulation. Following ovulation, the granulosa cells of the empty follicle luteinize
and transform into the progesterone-producing corpus luteum. The ovulated oocyte
with its surrounding granulosa cells is picked up by the infundibulum of the uterine
tube, and beating cilia help to transport it through the tube toward the uterus.
Fertilization occurs within the uterine tube, and the final stage of meiosis is completed.
The uterus has three regions: the fundus, the body, and the cervix. It has three
layers: the outer perimetrium, the muscular myometrium, and the inner endometrium.
The endometrium responds to estrogen released by the follicles during the menstrual
cycle, and grows thicker with an increase in blood vessels in preparation for
pregnancy. If the egg is not fertilized, no signal is sent to extend the life of the corpus
luteum, and it degrades, stopping progesterone production. This decline in
progesterone results in the sloughing of the inner portion of the endometrium in a
process called menses, or menstruation. The breasts are accessory sexual organs
that are utilized after the birth of a child to produce milk in a process called lactation.
Unique for its role in human reproduction, a gamete is a specialized sex cell
carrying 23 chromosomes—one half the number in body cells. At fertilization, the
chromosomes in one assigned male gamete, called a sperm (or spermatozoon),
combine with the chromosomes in one assigned female gamete, called an oocyte. The
function of the assigned male reproductive system, see Figure 27.2 is to produce
sperm and transfer them to the assigned female reproductive tract. The paired testes
are a crucial component in this process, as they produce both sperm and androgens,
the hormones that support assigned male reproductive physiology. In humans, the
most important assigned male androgen is testosterone. Several accessory organs
and ducts aid the process of sperm maturation and transport the sperm and other
seminal components to the penis, which delivers sperm to the assigned female
reproductive tract. In this section, we examine each of these different structures, and
discuss the process of sperm production and transport.
The testes are located in a skin-covered, highly pigmented, muscular sack called
the scrotum that extends from the body behind the penis see Figure 27.2. This location
is important in sperm production, which occurs within the testes, and proceeds more
efficiently when the testes are kept 2 to 4°C below core body temperature. The dartos
muscle makes up the subcutaneous muscle layer of the scrotum.
It continues internally to make up the scrotal septum, a wall that divides the
scrotum into two compartments, each housing one testis. Descending from the internal
oblique muscle of the abdominal wall are the two cremaster muscles, which cover
each testis like a muscular net. By contracting simultaneously, the dartos and
cremaster muscles can elevate the testes in cold weather (or water), moving the testes
closer to the body and decreasing the surface area of the scrotum to retain heat.
Alternatively, as the environmental temperature increases, the scrotum relaxes,
moving the testes farther from the body core and increasing scrotal surface area,
which promotes heat loss. Externally, the scrotum has a raised medial thickening on
the surface called the raphae.
The testes (singular = testis) are the assigned male gonads—that is, the
assigned male at birth’s reproductive organs. They produce both sperm and
androgens, such as testosterone, and are active throughout the reproductive lifespan.
Paired ovals, the testes are each approximately 4 to 5 cm in length and are housed
within the scrotum.They are surrounded by two distinct layers of protective connective
tissue. The outer tunica vaginalis is a serous membrane that has both a parietal and
a thin visceral layer. Beneath the tunica vaginalis is the tunica albuginea, a tough,
white, dense connective tissue layer covering the testis itself. Not only does the tunica
albuginea cover the outside of the testis, it also invaginates (turns inside out or folds
back on itself) to form septa that divide the testis into 300 to 400 structures called
lobules. Within the lobules, sperm develop in structures called seminiferous tubules.
During the seventh month of the developmental period of an assigned male fetus,
each testis moves through the abdominal musculature to descend into the scrotal
cavity. This is called the “descent of the testis.” Cryptorchidism is the clinical term used
when one or both of the testes does not descend into the scrotum prior to birth.
The tightly coiled seminiferous tubules form the bulk of each testis. They are
composed of developing sperm cells surrounding a lumen, the hollow center of the
tubule, where formed sperm are released into the duct system of the testis.
Specifically, from the lumens of the seminiferous tubules, sperm move into the straight
tubules (or tubuli recti), and from there into a fine meshwork of tubules called the rete
testes. Sperm leave the rete testes, and the testis itself, through the 15 to 20 efferent
ductules that cross the tunica albuginea.
Inside the seminiferous tubules are six different cell types. These include
supporting cells called sustentacular cells, as well as five types of developing sperm
cells called germ cells. Germ cell development progresses from the basement
membrane—at the perimeter of the tubule—toward the lumen. Let’s look more closely
at these cell types.
Surrounding all stages of the developing sperm cells are elongate, branching
Sertoli cells. Sertoli cells are a type of supporting cell called a sustentacular cell, or
sustentocyte, that are typically found in epithelial tissue. Sertoli cells secrete signaling
molecules that promote sperm production and can control whether germ cells live or
die. Tight junctions between these sustentacular cells create the blood– testis barrier,
which keeps bloodborne substances from reaching the germ cells and, at the same
time, keeps surface antigens on developing germ cells from escaping into the
bloodstream, prompting an autoimmune response.
The least mature cells, the spermatogonia (singular = spermatogonium), line the
basement membrane inside the tubule. Spermatogonia are the stem cells of the testis,
which means that they are still able to differentiate into a variety of different cell types
throughout adulthood. Spermatogonia divide to produce primary and secondary
spermatocytes, then spermatids, which finally produce formed sperm. The process
that begins with spermatogonia and concludes with the production of sperm is called
spermatogenesis.
As just noted, spermatogenesis occurs in the seminiferous tubules that form the
bulk of each testis (see Figure 27.4). The process begins at puberty, after which time
sperm is produced constantly throughout life. One production cycle, from
spermatogonia through formed sperm, takes approximately 64 days. A new cycle
starts approximately every 16 days, although this timing is not synchronous across the
seminiferous tubules. Sperm counts—the total number of sperm produced— slowly
decline after age 35, and some studies suggest that smoking can lower sperm counts
irrespective of age. Two identical diploid cells result from spermatogonia mitosis. One
of these cells remains a spermatogonium, and the other becomes a primary
spermatocyte, the next stage in the process of spermatogenesis. As in mitosis, DNA
is replicated in a primary spermatocyte, before it undergoes a cell division called
meiosis I. During meiosis I each of the 23 pairs of chromosomes separates. This
results in two cells, called secondary spermatocytes, each with only half the number
of chromosomes. Now a second round of cell division (meiosis II) occurs in both of the
secondary spermatocytes. During meiosis II each of the 23 replicated chromosomes
divides, similar to what happens during mitosis. Thus, meiosis results in separating
the chromosome pairs. Eventually, the sperm are released into the lumen, and are
moved along a series of ducts in the testis toward a structure called the epididymis for
the next step of sperm maturation.
Sperm are smaller than most cells in the body; in fact, the volume of a sperm cell
is 85,000 times less than that of the ovum. Approximately 100 million to 300 million
sperm are produced each day, whereas the ovary typically releases only one oocyte
per month. As is true for most cells in the body, the structure of sperm cells speaks to
their function. Sperm have a distinctive head, mid-piece, and tail region (Figure 27.6).
The head of the sperm contains the extremely compact haploid nucleus with very little
cytoplasm. These qualities contribute to the overall small size of the sperm (the head
is only 5 μm long). A structure called the acrosome covers most of the head of the
sperm cell as a “cap” that is filled with lysosomal enzymes important for preparing
sperm to participate in fertilization. Tightly packed mitochondria fill the mid-piece of the
sperm. ATP produced by these mitochondria will power the flagellum, which extends
from the neck and the mid-piece through the tail of the sperm, enabling it to move the
entire sperm cell. The central strand of the flagellum, the axial filament, is formed from
one centriole inside the maturing sperm cell during the final stages of
spermatogenesis.
To fertilize an ovum, sperm must be moved from the seminiferous tubules in the
testes, through the epididymis, and—later during ejaculation—along the length of the
penis and out into the assigned female reproductive tract.
From the lumen of the seminiferous tubules, the immotile sperm are surrounded
by testicular fluid and moved to the epididymis (plural = epididymides), a coiled tube
attached to the testis where newly formed sperm continue to mature. Though the
epididymis does not take up much room in its tightly coiled state, it would be
approximately 6 m (20 feet) long if straightened. It takes an average of 12 days for
sperm to move through the coils of the epididymis, with the shortest recorded transit
time in humans being one day. Sperm enter the head of the epididymis and are moved
along predominantly by the contraction of smooth muscles lining the epididymal tubes.
As they are moved along the length of the epididymis, the sperm further mature and
acquire the ability to move under their own power. Once inside the assigned female
reproductive tract, they will use this ability to move independently toward the
unfertilized ovum. The more mature sperm are then stored in the tail of the epididymis
(the final section), until ejaculation occurs.
During ejaculation, sperm exit the tail of the epididymis and are pushed by
smooth muscle contraction to the ductus deferens (also called the vas deferens). The
ductus deferens is a thick, muscular tube that is bundled together inside the scrotum
with connective tissue, blood vessels, and nerves into a structure called the spermatic
cord. Because the ductus deferens is physically accessible within the scrotum, surgical
sterilization to interrupt sperm delivery can be performed by cutting and sealing a small
section of the ductus (vas) deferens. This procedure is called a vasectomy, and it is
an effective form of birth control. Although it may be possible to reverse a vasectomy,
clinicians consider the procedure permanent, and advise individuals to undergo it only
if they are certain they no longer wish to have children. Sperm make up only 5 percent
of the final volume of semen, the thick, milky fluid that the penis ejaculates. The bulk
of semen is produced by three critical accessory glands of the reproductive system:
the seminal vesicles, the prostate, and the bulbourethral glands.
As sperm pass through the ampulla of the ductus deferens at ejaculation, they
mix with fluid from the associated seminal vesicle (see Figure 27.2). The paired
seminal vesicles are glands that contribute approximately 60 percent of the semen
volume. Seminal vesicle fluid contains large amounts of fructose, which is used by the
sperm mitochondria to generate ATP to allow movement through the assigned female
reproductive tract. The fluid, now containing both sperm and seminal vesicle
secretions, next moves into the associated ejaculatory duct, a short structure formed
from the ampulla of the ductus deferens and the duct of the seminal vesicle. The paired
ejaculatory ducts transport the seminal fluid into the next structure, the prostate gland.
The centrally located prostate gland sits anterior to the rectum at the base of the
bladder surrounding the prostatic urethra (the portion of the urethra that runs within
the prostate). About the size of a walnut, the prostate is formed of both muscular and
glandular tissues. It secretes an alkaline, milky fluid to the passing seminal fluid—now
called semen—that is critical to first coagulate and then decoagulate the semen
following ejaculation. The temporary thickening of semen helps retain it within the
assigned female reproductive tract, providing time for sperm to utilize the fructose
provided by seminal vesicle secretions. When the semen regains its fluid state, sperm
can then pass farther into the assigned female reproductive tract. The prostate
normally doubles in size during puberty. At approximately age 25, it gradually begins
to enlarge again. Abnormal growth of the prostate, or benign prostatic hyperplasia
(BPH), can cause constriction of the urethra as it passes through the middle of the
prostate gland, leading to a number of lower urinary tract symptoms, such as a
frequent and intense urge to urinate, a weak stream, and a sensation that the bladder
has not emptied completely.
The final addition to semen is made by two bulbourethral glands (or Cowper’s
glands) that release a thick, salty fluid that lubricates the end of the urethra and the
vagina, and helps to clean urine residues from the penile urethra. The fluid from these
accessory glands is released after the sexual arousal, and shortly before the release
of the semen. It is therefore sometimes called pre-ejaculatory fluid . It is important to
note that, in addition to the lubricating proteins, it is possible for bulbourethral fluid to
pick up sperm already present in the urethra, and therefore it may be able to cause
pregnancy.
The penis is the organ of copulation (sexual intercourse). It is flaccid for non-
sexual actions, such as urination, and turgid and rod-like with sexual arousal. When
erect, the stiffness of the organ allows it to penetrate into the vagina and deposit
semen into the assigned female reproductive tract.
The shaft of the penis surrounds the urethra.The shaft is composed of three
column-like chambers of erectile tissue that span the length of the shaft. Each of the
two larger lateral chambers is called a corpus cavernosum (plural = corpora
cavernosa). Together, these make up the bulk of the penis. The corpus spongiosum,
which can be felt as a raised ridge on the erect penis, is a smaller chamber that
surrounds the spongy, or penile, urethra. The end of the penis, called the glans penis,
has a high concentration of nerve endings, resulting in very sensitive skin that
influences the likelihood of ejaculation (see Figure 27.2). The skin from the shaft
extends down over the glans and forms a collar called the prepuce (or foreskin). The
foreskin also contains a dense concentration of nerve endings, and both lubricate and
protect the sensitive skin of the glans penis. A surgical procedure called circumcision,
often performed for religious or social reasons, removes the prepuce, typically within
days of birth.
Both sexual arousal and REM sleep (during which dreaming occurs) can induce
an erection. Penile erections are the result of vasocongestion, or engorgement of the
tissues because of more arterial blood flowing into the penis than is leaving in the
veins. During sexual arousal, nitric oxide (NO) is released from nerve endings near
blood vessels within the corpora cavernosa and spongiosum. Release of NO activates
a signaling pathway, which results in relaxation of the smooth muscles that surround
the penile arteries, causing them to dilate. This dilation increases the amount of blood
that can enter the penis and induces the endothelial cells in the penile arterial walls to
also secrete NO and perpetuate the vasodilation. The rapid increase in blood volume
fills the erectile chambers, and the increased pressure of the filled chambers
compresses the thin-walled penile venules, preventing venous drainage of the penis.
The result of this increased blood flow to the penis and reduced blood return from the
penis is erection. Depending on the flaccid dimensions of a penis, it can increase in
size slightly or greatly during erection, with the average length of an erect penis
measuring approximately 15 cm or 5.9 inches.
Circumcision is a controversial procedure because it involves the mutilation of a
penis. Many people view circumcision as a cosmetic procedure and argue that
individuals should make their own decision regarding participating in the surgery once
they reach their 18th birthday. Many cultures practice the ritual of circumcision,
however, in recent decades; Australia, Canada, Ireland, New Zealand, and the United
Kingdom have seen a decline in the ritual of circumcision. Religion is typically a driving
force in the decision to participate in circumcision, however, it is not always the case.
While religion is a major driving force in the decision to circumcise a child, the decision
to circumcise an individual can involve hygiene in addition to a way to express faith.
In recent decades, the potential risks associated with circumcision which include
excessive bleeding, irritation to the head of the penis, the possibility of injury, or even
a higher chance of meatitis (inflammation of the opening of the penis) have made
many parents reconsider this elective surgical procedure.
Testosterone, an androgen, is a steroid hormone produced by Leydig cells. The
alternate term for Leydig cells, interstitial cells, reflects their location between the
seminiferous tubules in the testes. In assigned male embryos, testosterone is secreted
by Leydig cells by the seventh week of development, with peak concentrations
reached in the second trimester. This early release of testosterone results in the
anatomical differentiation of the sexual organs. In childhood, testosterone
concentrations are low. They increase during puberty, activating characteristic physical
changes and initiating spermatogenesis.
The continued presence of testosterone is necessary to keep the reproductive
system working properly, and Leydig cells produce approximately 6 to 7 mg of
testosterone per day. Testicular steroidogenesis (the manufacture of androgens,
including testosterone) results in testosterone concentrations that are 100 times higher
in the testes than in the circulation. Maintaining these normal concentrations of
testosterone promotes spermatogenesis, whereas low levels of testosterone can lead
to infertility. In addition to intratesticular secretion, testosterone is also released into
the systemic circulation and plays an important role in muscle development, bone
growth, the development of secondary sex characteristics, and maintaining libido in
both assigned males and assigned females. In assigned females, the ovaries secrete
small amounts of testosterone, although most is converted to estradiol. A small amount
of testosterone is also secreted by the adrenal glands in both assigned sexes.
The regulation of testosterone concentrations throughout the body is critical for
reproductive function. The intricate interplay between the endocrine system and the
reproductive system is shown in Figure 27.8. The regulation of Leydig cell production
of testosterone begins outside of the testes. The hypothalamus and the pituitary gland
in the brain integrate external and internal signals to control testosterone synthesis
and secretion. The regulation begins in the hypothalamus. Pulsatile release of a
hormone called gonadotropin-releasing hormone (GnRH) from the hypothalamus
stimulates the endocrine release of hormones from the pituitary gland. Binding of
GnRH to its receptors on the anterior pituitary gland stimulates release of the two
gonadotropins: luteinizing hormone (LH) and follicle stimulating hormone (FSH).
These two hormones are critical for reproductive function in assigned males and
assigned females. In assigned males, FSH binds predominantly to the Sertoli cells
within the seminiferous tubules to promote spermatogenesis.
When concentrations of testosterone in the blood reach a critical threshold,
testosterone itself will bind to androgen receptors on both the hypothalamus and the
anterior pituitary, inhibiting the synthesis and secretion of GnRH and LH, respectively.
When the blood concentrations of testosterone once again decline, testosterone no
longer interacts with the receptors to the same degree, and GnRH and LH are once
again secreted, stimulating more testosterone production. This same process occurs
with FSH and inhibin to control spermatogenesis.
Gametes are the reproductive cells that combine to form a zygote. Organs called
gonads produce the gametes, along with the hormones that regulate human
reproduction. The male gametes are called sperm. Spermatogenesis, the production
of sperm, occurs within the seminiferous tubules that make up most of the testis. The
scrotum is the muscular sac that holds the testes outside of the body cavity.
Spermatogenesis begins with mitotic division of spermatogonia (stem cells) to produce
primary spermatocytes that undergo the two divisions of meiosis to become secondary
spermatocytes, then the haploid spermatids. During spermiogenesis, spermatids are
transformed into spermatozoa (formed sperm). Upon release from the seminiferous
tubules, sperm are moved to the epididymis where they continue to mature. During
ejaculation, sperm exit the epididymis through the ductus deferens, a duct in the
spermatic cord that leaves the scrotum. The ampulla of the ductus deferens meets the
seminal vesicle, a gland that contributes fructose and proteins, at the ejaculatory duct.
The fluid continues through the prostatic urethra, where secretions from the prostate
are added to form semen. These secretions help the sperm to travel through the
urethra and into the assigned female reproductive tract. Secretions from the
bulbourethral glands protect sperm and cleanse and lubricate the penile (spongy)
urethra.
The penis is the assigned male organ of copulation. Columns of erectile tissue
called the corpora cavernosa and corpus spongiosum fill with blood when sexual
arousal activates vasodilatation in the blood vessels of the penis. Testosterone
regulates and maintains the sex organs and libido, and induces the physical changes
of puberty. Interplay between the testes and the endocrine system precisely controls
the production of testosterone with a negative feedback loop.
