Anatomy of the Egg Producing and Conducting Organs and Gestational Organs

Learning Objectives

By the end of this section, you will be able to:

  • Describe the structure and function of the egg producing and conducting organs
  • List the steps of oogenesis
  • Trace the path of an oocyte from ovary to fertilization, or to release from the body during menstruation

The egg producing and conducting (EPC) organs function to produce gametes and reproductive hormones, just like the SPC organs; however, it also has the additional task of potentially supporting a developing fetus and delivering it to the outside world. Unlike the SPC organs, the EPC organs are located primarily inside the pelvic cavity.  Ovaries are the gonads, and the gamete they produce is called an oocyte (egg). We’ll discuss the production of oocytes in detail shortly. First, let’s look at some of the EPC organs.

Figure 1. The major egg producing and conducting organs are located inside the pelvic cavity.

External Genitals of those with EPC Organs

The external genitalia of those with EPC organs 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 medial to the labia majora. Although they naturally vary in shape and size, the labia minora serve to protect the urethra and the entrance to the EPC organs.

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 that 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 that intercourse has never occurred (“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 penile–vaginal intercourse. The vaginal opening is located between the opening of the urethra and the anus. It is flanked by outlets to the greater vestibular glands  (or Bartholin’s glands).

Figure 2. The external genitalia of those with EPC organs are referred to collectively as the vulva.

Vagina

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 hymen can be ruptured with strenuous physical exercise, penile–vaginal intercourse, and childbirth. The greater vestibular  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. The most predominant type of endogenous 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. However, douching—or washing out the vagina with fluid—can disrupt the normal balance of healthy microorganisms, and actually increase a woman’s risk for infections and irritation. Indeed, the American College of Obstetricians and Gynecologists recommend not to douche, in order to allow the vagina to maintain its normal healthy population of protective microbial flora.

Ovaries

The ovaries are the gonads of the EPC organs. 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 that 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. The growth and development of ovarian follicles will be described shortly. Beneath the cortex lies the inner ovarian medulla, the site of blood vessels, lymph vessels, and the nerves of the ovary.

The Ovarian Cycle

The ovarian cycle is a set of predictable changes in the oocytes and ovarian follicles.  Beginning at puberty and ending at menopause, the ovarian cycle 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 gametes) and folliculogenesis (the growth and development of ovarian follicles).

Oogenesis

Gametogenesis that produces an oocyte capable of fertilization 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 near menopause. The number of primary oocytes present in the ovaries declines from one 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, 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 in Figure 3, 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.

This flowchart shows the formation of oocytes in the female. The top half of the flowchart is before birth and the bottom half is after puberty. A callout to the left also shows the eggs before and after sperm penetration.

Figure 3. Click for a larger image. 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 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 secondary oocyte and diploid zygote.

The larger amount of cytoplasm contained in the oocyte 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 originate from the egg-producing parent. This includes mitochondria, which contain their own DNA. Scientific research in the 1980s determined that mitochondrial DNA was inherited from the ovum, meaning that you can trace your mitochondrial DNA directly to your egg-producing parent, their egg-producing parent, and so on back through your ancestors with EPC organs.

Everyday Connections: Mapping Human History with Mitochondrial DNA

When we talk about human DNA, we’re usually referring to nuclear DNA; that is, the DNA coiled into chromosomal bundles in the nucleus of our cells. We inherit half of our nuclear DNA from our sperm-producing parent, and half from our egg-producing parent. However, mitochondrial DNA (mtDNA) comes only from the mitochondria in the cytoplasm of the ovum we inherit from our egg-producing parent. That mtDNA was inherited from their egg-producing parent, who got it from their egg-producing parent, and so on. Each of our cells contains approximately 1700 mitochondria, with each mitochondrion packed with mtDNA containing approximately 37 genes.

Mutations (changes) in mtDNA occur spontaneously in a somewhat organized pattern at regular intervals in human history. By analyzing these mutational relationships, researchers have been able to determine that we can all trace our ancestry back to one person with EPC organs who lived in Africa about 200,000 years ago. Scientists have given this person the biblical name “Eve”, although they are not, of course, the first Homo sapiens with EPC organs. More precisely, they are our most recent common ancestor to provide mtDNA.

This doesn’t mean that everyone’s mtDNA today looks exactly like that of our ancestral “Eve”. Because of the spontaneous mutations in mtDNA that have occurred over the centuries, researchers can map different “branches” off of the “main trunk” of our mtDNA family tree. Your mtDNA might have a pattern of mutations that aligns more closely with one branch, and your neighbor’s may align with another branch. Still, all branches eventually lead back to “Eve”.

But what happened to the mtDNA of all of the other Homo sapiens with EPC organs who were living at the time of “Eve”? Researchers explain that, over the centuries, their descendants either died childless or only with children who had SPC organs, and thus their line of mtDNA ended.

Folliculogenesis

Again, 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, an infant with EPC organs at birth will have one to two million oocytes within their ovarian follicles, and that this number declines throughout life until menopause, when no follicles remain. As you’ll see next, 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. 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.

After puberty, a few primordial follicles will respond to a recruitment signal each day, and will join a pool of immature growing follicles called primary follicles. Primary follicles start with a single layer of granulosa cells, but the granulosa cells then become active and transition from a flat or squamous shape to a rounded, cuboidal shape as they increase in size and proliferate. As the granulosa cells divide, the follicles—now called secondary follicles—increase in diameter, adding a new outer layer of connective tissue, blood vessels, and theca cells—cells that work with the granulosa cells to produce estrogens.

Within the growing secondary follicle, the primary oocyte now secretes a thin acellular membrane called the zona pellucida that will play a critical role in fertilization. A thick fluid, called follicular fluid, that has formed between the granulosa cells also begins to collect into one large pool, or antrum. Follicles in which the antrum has become large and fully formed are considered tertiary follicles (or antral follicles). Several follicles reach the tertiary stage at the same time, and most of these will undergo atresia. The one that does not die will continue to grow and develop until ovulation, when it will expel its secondary oocyte surrounded by several layers of granulosa cells from the ovary. Keep in mind that most follicles don’t make it to this point. In fact, roughly 99 percent of the follicles in the ovary will undergo atresia, which can occur at any stage of folliculogenesis.

This multipart figure shows how follicles are generated. The top panel shows the six stages of folliculogenesis. In each stage, the major cell types are labeled. The bottom part shows a micrograph of a secondary follicle and the major parts are labeled.

Figure 4. Click for a larger image. (a) The maturation of a follicle is shown in a clockwise direction proceeding from the primordial follicles. FSH stimulates the growth of a tertiary follicle, and LH stimulates the production of estrogen by granulosa and theca cells. Once the follicle is mature, it ruptures and releases the oocyte. Cells remaining in the follicle then develop into the corpus luteum. (b) In this electron micrograph of a secondary follicle, the oocyte, theca cells (thecae folliculi), and developing antrum are clearly visible. EM × 1100. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)

The Uterine Tubes

The uterine tubes (also called fallopian tubes or oviducts) serve as the conduit of the oocyte from the ovary to the uterus. Each of the two uterine 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 uterine 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 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, 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. 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 egg while it is still moving through the ampulla.

Practice Question

Watch this video to observe ovulation and its initiation in response to the release of FSH and LH from the pituitary gland. What specialized structures help guide the oocyte from the ovary into the uterine tube?

If the oocyte is successfully fertilized, the resulting zygote will begin to divide into two cells, then four, and so on, as it makes its way through the uterine tube and into the uterus. There, it will implant and continue to grow. If the egg is not fertilized, it will simply degrade—either in the uterine tube or in the uterus, where it may be shed with the next menstrual period.

This diagram shows the uterus and ovaries in the center. To the left is a micrograph showing the ultrastructure of the ovaries and to the right is a micrograph showing the ultrastructure of the uterus.

Figure 6. This anterior view shows the relationship of the ovaries, uterine tubes (oviducts), and uterus. Sperm enter through the vagina, and fertilization of an ovulated oocyte usually occurs in the distal uterine tube. From left to right, LM × 400, LM × 20. (Micrographs provided by the Regents of University of Michigan Medical School © 2012)

The open-ended structure of the uterine tubes can have significant health consequences if bacteria or other contagions enter through the vagina and move through the uterus, into the tubes, and then into the pelvic cavity. If this is left unchecked, a bacterial infection (sepsis) could quickly become life-threatening. The spread of an infection in this manner is of special concern when unskilled practitioners perform abortions in non-sterile conditions. Sepsis is also associated with sexually transmitted bacterial infections, especially gonorrhea and chlamydia. These increase the risk for pelvic inflammatory disease (PID), infection of the uterine tubes or other reproductive organs. Even when resolved, PID can leave scar tissue in the tubes, leading to infertility.

Practice Question

Watch this series of videos to look at the movement of the oocyte through the ovary. The cilia in the uterine tube promote movement of the oocyte. What would likely occur if the cilia were paralyzed at the time of ovulation?

The Uterus and Cervix

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), but it increases greatly in size during pregnancy. 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 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 menstrual blood during menses (a period). Anteriorly directed myometrial contractions also occur near the time of ovulation, and are thought to possibly facilitate the transport of sperm through the egg conducting organs.

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 off 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 egg, 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 post-ovulatory 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.

 

Disorders of EPC Organs

Research over many years has confirmed that cervical cancer is most often caused by a sexually transmitted infection with human papillomavirus (HPV). There are over 100 related viruses in the HPV family, and the characteristics of each strain determine the outcome of the infection. In all cases, the virus enters body cells and uses its own genetic material to take over the host cell’s metabolic machinery and produce more virus particles.

HPV infections are common in both those with EPC and SPC organs. A recent study determined that 42.5 percent of individuals with EPC organs had HPV at the time of testing. These individuals ranged in age from 14 to 59 years and differed in race, ethnicity, and number of sexual partners. Of note, the prevalence of HPV infection was 53.8 percent among women aged 20 to 24 years, the age group with the highest infection rate.

HPV strains are classified as high or low risk according to their potential to cause cancer. Though most HPV infections do not cause disease, the disruption of normal cellular functions in the low-risk forms of HPV can cause the human host to develop genital warts. Often, the body is able to clear an HPV infection by normal immune responses within 2 years. However, the more serious, high-risk infection by certain types of HPV can result in cancer of the cervix. Infection with either of the cancer-causing variants HPV 16 or HPV 18 has been linked to more than 70 percent of all cervical cancer diagnoses. Although even these high-risk HPV strains can be cleared from the body over time, infections persist in some individuals. If this happens, the HPV infection can influence the cells of the cervix to develop precancerous changes.

Risk factors for cervical cancer include having unprotected sex; having multiple sexual partners; a first sexual experience at a younger age, when the cells of the cervix are not fully mature; failure to receive the HPV vaccine; a compromised immune system; and smoking. The risk of developing cervical cancer is doubled with cigarette smoking.

The left panel shows cell cycle. An arrow from the G2 phase leads to the right panel. The top half of the right panel describes the next steps in the absence of HPV and the bottom half describes the next steps in the presence of HPV.

Figure 8. In most cases, cells infected with the HPV virus heal on their own. In some cases, however, the virus continues to spread and becomes an invasive cancer.

 

When the high-risk types of HPV enter a cell, two viral proteins are used to neutralize proteins that the host cells use as checkpoints in the cell cycle. The best studied of these proteins is p53. In a normal cell, p53 detects DNA damage in the cell’s genome and either halts the progression of the cell cycle—allowing time for DNA repair to occur—or initiates apoptosis. Both of these processes prevent the accumulation of mutations in a cell’s genome. High-risk HPV can neutralize p53, keeping the cell in a state in which fast growth is possible and impairing apoptosis, allowing mutations to accumulate in the cellular DNA.

The prevalence of cervical cancer in the United States is very low because of regular screening exams called pap smears. Pap smears sample cells of the cervix, allowing the detection of abnormal cells. If pre-cancerous cells are detected, there are several highly effective techniques that are currently in use to remove them before they pose a danger. However, people in developing countries often do not have access to regular pap smears. As a result, they account for as many as 80 percent of the cases of cervical cancer worldwide.

In 2006, the first vaccine against the high-risk types of HPV was approved. There are now two HPV vaccines available: Gardasil® and Cervarix®. Whereas these vaccines were initially only targeted for those with EPC organs, because HPV is sexually transmitted, both those with EPC and SPC organs require vaccination for this approach to achieve its maximum efficacy. A recent study suggests that the HPV vaccine has cut the rates of HPV infection by the four targeted strains at least in half. Unfortunately, the high cost of manufacturing the vaccine is currently limiting access to many people worldwide.

The Breasts

Whereas the breasts are located far from the other gestational organs, they are considered accessory gestational organs, as they act to sustain a baby after it is born. 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, 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. 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 that connect the breast tissue to the dermis of the overlying skin.

This figure shows the anatomy of the breast. The left panel shows the front view and the right panel shows the side view. The main parts are labeled.

Figure 9. During lactation, milk moves from the alveoli through the lactiferous ducts to the nipple.

During the normal 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.

 

Aging and the EPC organs

Fertility (the ability to conceive) for those with EPC organs peaks when individuals are in their twenties, and is slowly reduced until 35 years of age. After that time, fertility declines more rapidly, until it ends completely at the end of menopause. Menopause is the cessation of the menstrual cycle that occurs as a result of the loss of ovarian follicles and the hormones that they produce. A person is considered to have completed menopause if they has not menstruated in a full year. After that point, they are considered postmenopausal. The average age for this change is consistent worldwide at between 50 and 52 years of age, but it can normally occur in a person’s forties, or later in their fifties. Poor health, including smoking, can lead to earlier loss of fertility and earlier menopause.

As a someone reaches the age of menopause, depletion of the number of viable follicles in the ovaries due to atresia affects the hormonal regulation of the menstrual cycle. During the years leading up to menopause, there is a decrease in the levels of the hormone inhibin, which normally participates in a negative feedback loop to the pituitary to control the production of FSH. The menopausal decrease in inhibin leads to an increase in FSH. The presence of FSH stimulates more follicles to grow and secrete estrogen. Because small, secondary follicles also respond to increases in FSH levels, larger numbers of follicles are stimulated to grow; however, most undergo atresia and die. Eventually, this process leads to the depletion of all follicles in the ovaries, and the production of estrogen falls off dramatically. It is primarily the lack of estrogens that leads to the symptoms of menopause.

The earliest changes occur during the menopausal transition, often referred to as peri-menopause, when a person’s cycle becomes irregular but does not stop entirely. Although the levels of estrogen are still nearly the same as before the transition, the level of progesterone produced by the corpus luteum is reduced. This decline in progesterone can lead to abnormal growth, or hyperplasia, of the endometrium. This condition is a concern because it increases the risk of developing endometrial cancer. Two harmless conditions that can develop during the transition are uterine fibroids, which are benign masses of cells, and irregular bleeding. As estrogen levels change, other symptoms that occur are hot flashes and night sweats, trouble sleeping, vaginal dryness, mood swings, difficulty focusing, and thinning of hair on the head along with the growth of more hair on the face. Depending on the individual, these symptoms can be entirely absent, moderate, or severe.

After menopause, lower amounts of estrogens can lead to other changes. Cardiovascular disease becomes as prevalent in those with EPC organs as in those with SPC organs, possibly because estrogens reduce the amount of cholesterol in the blood vessels. When estrogen is lacking, many people find that they suddenly have problems with high cholesterol and the cardiovascular issues that accompany it. Osteoporosis is another problem because bone density decreases rapidly in the first years after menopause. The reduction in bone density leads to a higher incidence of fractures.

Hormone therapy (HT), which employs medication (synthetic estrogens and progestins) to increase estrogen and progestin levels, can alleviate some of the symptoms of menopause. In 2002, the Women’s Health Initiative began a study to observe people with EPC organs for the long-term outcomes of hormone replacement therapy over 8.5 years. However, the study was prematurely terminated after 5.2 years because of evidence of a higher than normal risk of breast cancer in patients taking estrogen-only HT. The potential positive effects on cardiovascular disease were also not realized in the estrogen-only patients. The results of other hormone replacement studies over the last 50 years, including a 2012 study that followed over 1,000 menopausal individuals for 10 years, have shown cardiovascular benefits from estrogen and no increased risk for cancer. Some researchers believe that the age group tested in the 2002 trial may have been too old to benefit from the therapy, thus skewing the results. In the meantime, intense debate and study of the benefits and risks of replacement therapy is ongoing. Current guidelines approve HT for the reduction of hot flashes or flushes, but this treatment is generally only considered when individuals first start showing signs of menopausal changes, is used in the lowest dose possible for the shortest time possible (5 years or less), and it is suggested that those on HT have regular pelvic and breast exams.

Chapter Review

The external genitalia of those with EPC organs are collectively called the vulva. The vagina is the pathway into and out of the uterus. The 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 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 gestational organs that are utilized after the birth of a child to produce milk in a process called lactation. Birth control pills provide constant levels of estrogen and progesterone to negatively feed back on the hypothalamus and pituitary, and suppress the release of FSH and LH, which inhibits ovulation and prevents pregnancy.

Self Check

Answer the question(s) below to see how well you understand the topics covered in the previous section.

Critical Thinking Questions

  1. Follow the path of ejaculated sperm from the vagina to the oocyte. Include all structures of the EPC organs that the sperm must swim through to reach the egg.
  2. Identify some differences between meiosis in those with SPC or EPC organs.
  3. Explain the hormonal regulation of the phases of the menstrual cycle.
  4. Endometriosis is a disorder in which endometrial cells implant and proliferate outside of the uterus—in the uterine tubes, on the ovaries, or even in the pelvic cavity. Offer a theory as to why endometriosis increases the risk of infertility.

Glossary

alveoli: (of the breast) milk-secreting cells in the mammary gland

ampulla: (of the uterine tube) middle portion of the uterine tube in which fertilization often occurs

antrum: fluid-filled chamber that characterizes a mature tertiary (antral) follicle

areola: highly pigmented, circular area surrounding the raised nipple and containing areolar glands that secrete fluid important for lubrication during suckling

body of uterus: middle section of the uterus

broad ligament: wide ligament that supports the uterus by attaching laterally to both sides of the uterus and pelvic wall

cervix: elongate inferior end of the uterus where it connects to the vagina

clitoris: (also, glans clitoris) nerve-rich area of the vulva that contributes to sexual sensation during intercourse

corpus albicans: nonfunctional structure remaining in the ovarian stroma following structural and functional regression of the corpus luteum

corpus luteum: transformed follicle after ovulation that secretes progesterone

endometrium: inner lining of the uterus, part of which builds up during the secretory phase of the menstrual cycle and then sheds with menses

fimbriae: fingerlike projections on the distal uterine tubes

follicle: ovarian structure of one oocyte and surrounding granulosa (and later theca) cells

folliculogenesis: development of ovarian follicles from primordial to tertiary under the stimulation of gonadotropins

fundus: (of the uterus) domed portion of the uterus that is superior to the uterine tubes

granulosa cells: supportive cells in the ovarian follicle that produce estrogen

greater vestibular glands: glands that produce a thick mucus that maintains moisture in the vulva area; also referred to as  Bartholin’s glands

hymen: membrane that covers part of the opening of the vagina

infundibulum: (of the uterine tube) wide, distal portion of the uterine tube terminating in fimbriae

isthmus: narrow, medial portion of the uterine tube that joins the uterus

labia majora: hair-covered folds of skin located behind the mons pubis

labia minora: thin, pigmented, hairless flaps of skin located medial and deep to the labia majora

lactiferous ducts: ducts that connect the mammary glands to the nipple and allow for the transport of milk

lactiferous sinus: area of milk collection between alveoli and lactiferous duct

mammary glands: glands inside the breast that secrete milk

menarche: first menstruation in a pubertal individual

menses: shedding of the inner portion of the endometrium out though the vagina; also referred to as menstruation

menses phase: phase of the menstrual cycle in which the endometrial lining is shed

menstrual cycle: approximately 28-day cycle of changes in the uterus consisting of a menses phase, a proliferative phase, and a secretory phase

mons pubis: mound of fatty tissue located at the front of the vulva

myometrium: smooth muscle layer of uterus that allows for uterine contractions during labor and expulsion of menstrual blood

oocyte: gamete that results from the division of the oogonium and undergoes meiosis I at the LH surge and meiosis II at fertilization to become a haploid ovum

oogenesis: process by which oogonia divide by mitosis to primary oocytes, which undergo meiosis to produce the secondary oocyte and, upon fertilization, the ovum

oogonia: ovarian stem cells that undergo mitosis during fetal development of those with EPC organs to form primary oocytes

ovarian cycle: approximately 28-day cycle of changes in the ovary consisting of a follicular phase and a luteal phase

ovaries: gonads of those with EPC organs that produce oocytes and sex steroid hormones (notably estrogen and progesterone)

ovulation: release of a secondary oocyte and associated granulosa cells from an ovary

ovum: haploid gamete of those with EPC organs resulting from completion of meiosis II at fertilization

perimetrium: outer epithelial layer of uterine wall

polar body: smaller cell produced during the process of meiosis in oogenesis

primary follicles: ovarian follicles with a primary oocyte and one layer of cuboidal granulosa cells

primordial follicles: least developed ovarian follicles that consist of a single oocyte and a single layer of flat (squamous) granulosa cells

proliferative phase: phase of the menstrual cycle in which the endometrium proliferates

rugae: (of the vagina) folds of skin in the vagina that allow it to stretch during intercourse and childbirth

secondary follicles: ovarian follicles with a primary oocyte and multiple layers of granulosa cells

secretory phase: phase of the menstrual cycle in which the endometrium secretes a nutrient-rich fluid in preparation for implantation of an embryo

suspensory ligaments: bands of connective tissue that suspend the breast onto the chest wall by attachment to the overlying dermis

tertiary follicles: (also, antral follicles) ovarian follicles with a primary or secondary oocyte, multiple layers of granulosa cells, and a fully formed antrum

theca cells: estrogen-producing cells in a maturing ovarian follicle

uterine tubes: (also, fallopian tubes or oviducts) ducts that facilitate transport of an ovulated oocyte to the uterus

uterus: muscular hollow organ in which a fertilized egg develops into a fetus

vagina: tunnel-like organ that provides access to the uterus for the deposition of semen, and from the uterus for the birth of a baby

vulva: external genitalia of those with EPC organs