Wk5 Ch17.13: female reproduction- ovarian functions

• The ovary, like the testis, serves several functions:
• (1) oogenesis, the production of gametes during the fetal period;
• (2) maturation of the oocyte;
• (3) expulsion of the mature oocyte (ovulation); and
• (4) secretion of the female sex steroid hormones (estrogen and progesterone), as well as the protein hormone inhibin.
• Before ovulation, the maturation of the oocyte and endocrine functions of the ovaries take place in a single structure, the follicle.
• After ovulation, the follicle, now without an egg, differentiates into a corpus luteum, the functions of which are described later.

• At birth, the ovaries contain an estimated 2 to 4 million eggs, and no new ones appear after birth.
• Only a few, perhaps 400, will be ovulated during a woman’s lifetime.
• All the others degenerate at some point in their development so that few, if any, remain by the time a woman reaches approximately 50 years of age.
• One result of this developmental pattern is that the eggs ovulated near age 50 are 35 to 40 years older than those ovulated just after puberty.
• It is possible that certain chromosomal defects more common among children born to older women are the result of aging changes in the egg.

• During early fetal development, the primitive germ cells, or oogonia (singular, oogonium) undergo numerous mitotic divisions (Figure 17.19).
• Oogonia are analogous to spermatogonia in the male (see Figure 17.1).
• Around the seventh month of gestation, the fetal oogonia cease dividing. Current thinking is that from this point on, no new germ cells are generated.

• During fetal life, all the oogonia develop into primary oocytes (analogous to primary spermatocytes), which then begin a first meiotic division by replicating their DNA.
• They do not, however, complete the division in the fetus.
• Accordingly, all the eggs present at birth are primary oocytes containing 46 chromosomes, each with two sister chromatids.
• The cells are said to be in a state of meiotic arrest.
• 

• All the eggs present at birth- primary oocytes containing 46 chromosomes, each with two sister chromatids.
• Don't start meiosis until puberty.
• This state continues until puberty and the onset of renewed activity in the ovaries.

• Indeed, only those primary oocytes destined for ovulation will complete the first meiotic division, for it occurs just before the egg is ovulated.
• This division is analogous to the division of the primary spermatocyte, and each daughter cell receives 23 chromosomes, each with two chromatids.
• In this division, however, one of the two daughter cells, the secondary oocyte, retains virtually all the cytoplasm.
• The other, the first polar body, is very small and nonfunctional.
• The primary oocyte, which is already as large as the egg will be, passes on to the secondary oocyte just half of its chromosomes but almost all of its nutrient-rich cytoplasm.
• 

• The second meiotic division occurs in a fallopian tube after ovulation, but only if the secondary oocyte is fertilized—that is, penetrated by a sperm.
• As a result of this second meiotic division, the daughter cells each receive 23 chromosomes, each with a single chromatid.
• Once again, one daughter cell retains nearly all the cytoplasm.
• The other daughter cell, the second polar body, is very small and nonfunctional.
• The net result of oogenesis is that each primary oocyte can produce only one
• ovum. In contrast, each primary spermatocyte produces four viable spermatozoa.
• 

Throughout their life in the ovaries, the eggs exist in structures known as follicles.

• Follicles begin as primordial follicles, which consist of one primary oocyte surrounded by a single layer of cells called granulosa cells.
• 

The granulosa cells secrete estrogen, small amounts of progesterone (just before ovulation), and inhibin.

• Further development from the primordial follicle stage (Figure 17.20) is characterized by an increase in the size of the oocyte; a proliferation of the granulosa cells into multiple layers;
• and the separation of the oocyte from the inner granulosa cells by a thick layer of material, the zona pellucida, secreted by the surrounding follicular cells.
• The zona pellucida contains glycoproteins that have a function in the binding of a sperm cell to the surface of an egg after ovulation.
• Despite the presence of a zona pellucida, the inner layer of granulosa cells remains closely associated with the oocyte by means of cytoplasmic processes that traverse the zona pellucida and form gap junctions with the oocyte.
• Through these gap junctions, nutrients and chemical messengers are passed to the oocyte.
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• A thick layer of material, the zona pellucida, secreted by the surrounding follicular cells.
• Between inner granulosa cells and oocyte.
• The zona pellucida contains glycoproteins that have a function in the binding of a sperm cell to the surface of an egg after ovulation.
• 

• As the follicle grows by proliferation of granulosa cells, connective-tissue cells surrounding the granulosa cells differentiate and form layers of cells known as the theca, which function together with the granulosa cells in the synthesis of estrogen.
• 

• The theca: layers of cells, which function together with the granulosa cells in the synthesis of estrogen.
• Created through differentiation of the connective-tissue cells surrounding the granulosa cells.
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• Shortly after this, the primary oocyte reaches full size (∼115 μm in diameter), and a fluid-filled space, the antrum, begins to form in the midst of the granulosa cells as a result of fluid they secrete.
• The progression of some primordial follicles to the preantral and early antral stages (see Figure 17.20) occurs throughout infancy and childhood and then during the entire menstrual cycle.
• Therefore, although most of the follicles in the ovaries are still primordial, a nearly constant number of preantral and early antral follicles are also always present.
• 

• At the beginning of each menstrual cycle, 10 to 25 of these preantral and early antral follicles begin to develop into larger antral follicles.
• About one week into the cycle, a further selection process occurs: Only one of the larger antral follicles, the dominant follicle, continues to develop.
• The exact process by which a follicle is selected for dominance is not known, but it is likely related to the amount of estrogen produced locally within the follicle.
• (This is probably why hyperstimulation of infertile women with gonadotropin injections can result in the maturation of many follicles.)
• The nondominant follicles (in both ovaries) that had begun to enlarge undergo a degenerative process called atresia, which is an example of programmed cell death, or apoptosis. The eggs in the degenerating follicles also die.

• The nondominant follicles (in both ovaries) that had begun to enlarge undergo a degenerative process called atresia, which is an example of programmed cell death, or apoptosis.
• The eggs in the degenerating follicles also die.
• Atresia is not limited to just antral follicles, however, for follicles can undergo atresia at any stage of development.
• Indeed, this process is already occurring in the female fetus, so that the
• 2 to 4 million follicles and eggs present at birth represent only a small fraction of those present earlier in gestation.
• Atresia then continues all through prepubertal life so that only 200,000 to 400,000 follicles remain when active reproductive life begins.
• Of these, all but about 400 will undergo atresia during a woman’s reproductive life.
• Therefore, 99.99% of the ovarian follicles present at birth will undergo atresia.

• Also called a graafian follicle.
• The dominant follicle enlarges as a result of an increase in fluid, causing the antrum to expand.
• As this occurs, the granulosa cell layers surrounding the egg form a mound that projects into the antrum and is called the cumulus oophorus (see Figure 17.20).
• As the time of ovulation approaches, the egg (a primary oocyte) emerges from meiotic arrest and completes its first meiotic division to become a secondary oocyte.
• The cumulus separates from the follicle wall so that it and the oocyte float free in the antral fluid. The mature follicle (also called a graafian follicle) becomes so large (diameter about 1.5 cm) that it balloons out on the surface of the ovary.
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• Cumulus oophorous: when the granulosa cell layers surrounding the egg form a mound that projects into the atrum
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• Ovulation occurs when the thin walls of the follicle and ovary rupture at the site where they are joined because of enzymatic digestion.
• The secondary oocyte, surrounded by its tightly adhering zona pellucida and granulosa cells, as well as the cumulus, is carried out of the ovary and onto the ovarian surface by the antral fluid.
• All this happens on approximately day 14 of the menstrual cycle.

• Occasionally, two or more follicles reach maturity, and more than one egg may be ovulated. This is the more common cause of multiple births.
• In such cases, the siblings are fraternal (dizygotic) twins, not identical, because the eggs carry different sets of genes and are fertilized by different sperm.

• After the mature follicle discharges its antral fluid and egg, it collapses around the antrum and undergoes a rapid transformation.
• The granulosa cells enlarge greatly, and the entire glandlike structure formed is called the corpus luteum, which secretes estrogen, progesterone, and inhibin.
• If the discharged egg, now in a fallopian tube, is not fertilized by fusing with a sperm cell, the corpus luteum reaches its maximum development within approximately 10 days.
• It then rapidly degenerates by apoptosis.
• As we will see, it is the loss of corpus luteum function that leads to menstruation and the beginning of a new menstrual cycle.

• In terms of ovarian function, therefore, the menstrual cycle may be divided into two phases approximately equal in length and separated by ovulation (Figure 17.21)
• (1) the follicular phase, during which a mature follicle and secondary oocyte develop; and
• (2) the luteal phase, beginning after ovulation and lasting until the death of the corpus luteum.
• As you will see, these ovarian phases correlate with and control the changes in the appearance of the uterine lining (to be described subsequently).
• 
• Figure 17.21 Summary of ovarian events during a menstrual cycle (if fertilization does not occur). The first day of the cycle is named for a uterine event—the onset of bleeding—even though ovarian events are used to denote the cycle phases.

• The synthesis of gonadal steroids was introduced in Figure 17.6 and can be summarized as follows.
• Estrogen (primarily estradiol and estrone) is synthesized and released into the blood during the follicular phase mainly by the granulosa cells.
• After ovulation, estrogen is synthesized and released by the corpus luteum.
• Progesterone, the other major ovarian steroid hormone, is synthesized and released in very small amounts by the granulosa and theca cells just before ovulation, but its major source is the corpus luteum.
• Inhibin is secreted by both the granulosa cells and the corpus luteum.