74: Histology of Female Reproductive System

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How does LH and FSH influence ovulation?

Ovulatory surges of LH and FSH change the signaling between granulosa cells and the oocyte. LH surge causes release of growth factors that are insulin factors that degrade cAMP and allow meiosis I to finish.

Proliferative phase

Proliferative phase is 6-14 days: an increase in estrogen levels during the follicular phase stimulates endometrium growth (thickness) and spiral arteries grow. increase in vascular supply and develops exocrine secreting uterine glands.

Cortical granules

Release enzymes that alter the zona pellucida, causing it to become impermeable to other sperm (block to polyspermy).

Theca interna

Secreting androgens which are converted into estrogens by the granulosa cells; it lies adjacent to basal lamina of granulosa cells.

Secretory phase

Secretory phase is 14-28: uterine glands in the endometrium secrete uterine milk into the uterus to nourish the developing egg. stimulated by an increase in progesterone levels during the luteal phase.

Why Does Estrogen Initially Depress LH and Then Stimulate the LH Surge?

Some LH receptor hormone neurons have an alpha-type estrogen receptor that suppresses their function; while some neurons have a beta-type estrogen receptor that stimulates their function.

How can sperm fertilize the egg?

Sperm have to penetrate corona radiata which is rich in hyaluronic acid and the zona pellucida (glycoprotein coat). Follicular fluid fills the antrum of the follicle; the follicular fluid is rich in hyaluronic acid.

cervix

Stratified non-keratinizing squamous epithelium. Merges at the transformation zone (squamocolumnar junction) to endocervix lined by tall mucinous columnar cells. The endocervix has underlying endocervicalglands that are also lined by tall mucinous columnar cells.

Cervical cancer

The 2nd most common form of cancer and accounts for 10% of all cancers and is caused by HPV which causes the basal cells to over-proliferate and invade the underlying connective tissue. Most often occurs at the squamocolumnar junction. Prevention includes HPV vaccine, safe sex and regular PAP smears for early detection. Treatment includes hysterectomy or removal of the cervix.

What happens after 12 days if fertilization does not occur?

The corpus luteum regresses, stops secreting hormones, and becomes a Corpus Albicans. This causes a reduction in estrogen and progesterone (endometrial lining sheds). This also causes secretion of GnRH, FSH and LH allowing the cycle to begin again.

What happens if fertilization does occur?

The fertilized egg secretes a hormone called human chorionic gonadotropin (hCG) which stimulates the anterior pituitary gland for continued secretion of LH and prevents the degradation of the corpus luteum (for continued progesterone).

What are the regions of the oviducts?

The fimbriae pick up the released ovum, then the infundibulum, the ampulla is the widest portions and where fertilization occurs. The isthmus is the connection between fallopian tube and interstitial part of the uterus. The smooth muscle layer increases across the fallopian tube as you move closer towards the uterus.

What is completed at ovulation?

The first meiotic division with formation of the first polar body

Follicular phase

The follicular phase of the ovarian cycle is day 1-14. GnRH from the hypothalamus stimulates FSH and LH secretion from the anterior pituitary gland. (growth) of the follicular cells of a primordial follicle developing into a primary follicle. , which continues to grow into a secondary and tertiary follicle.

Corona radiata

The most inner layer of the granulosa cells surrounding the oocyte which is adjacent to the zona pelucida. Corona radiata main purpose is to supply vital proteins to the oocyte.

ovarian cycle

The ovarian cycle is controlled by GnRH, FSH, LH which target the ovaries; stimulate estrogen & progesterone secretion.

What are the regions of the uterus?

There are three regions: cervix (neck that connects to vagina), body (large middle portion), and fundus (rounded superior region that connects to the fallopian tubes).

Follicular Atresia

When follicles lose their egg and collapse due to apoptosis of granular cells and engulfment by macrophages. In menopause women, still have follicles that can be stimulated to mature; they do not all undergo atresia.

germinal epithelium of Waldeyer

a layer of simple squamous-to-cuboidal epithelial cells covering the ovary; but it does NOT give rise to primary follicles

When does meiosis II begin?

fertilization

What travels with the the egg (oocyte) as it is released in the fallopian tube?

many corona radiata cells

What are the 3 parts of the uterine cycle?

menstrual phase, proliferative phase, and secretory phase

internal genitalia

ovaries, uterus, fallopian tubes and vagina

ovaries

primordial follicles and each consist of an oocyte (immature egg cell) surrounded by a single layer of simple squamous follicle cells.

external genitalia of female

the vulva, the labia majora & minora, and clitoris

uterus

A hollow, thick walled organ located in the pelvis, superior to the vagina which provides an ideal location for the implantation and 9-month development of a fertilized ovum.

vagina

A thin-walled tube lying posterior to the bladder and anterior to the rectum. It is the organ of intercourse and connects the external environment to the uterus. The vagina has a stratified squamous epithelium supported by lamina propria with many lymph vessels. There is longitudinal smooth muscles layer and transverse smooth muscle layer. Then a serous adventitia.

Luteal Phase

After ovulation, you enter the luteal phase which is day 14-28. In the Luteal phase, LH decreases, and the ruptured follicle becomes the corpus luteum, which makes progesterone to prepare the uterus for pregnancy. In the corpus luteum, granulosa cells increase in size and become granulosa lutein cells and the Theca interna cells are transformed into theca lutein cells which secrete estrogen and progesterone and penetrate the masses of granulosa cells. The corpus luteum is quite large and takes up space in the ovary. Granulosa Lutein cells constitute majority of the cells, also stain positively for a peptide hormone called Relaxin which is stored in secretory granules. Relaxin increases enzymes within the cervix that weaken it; may cause premature birth.

Secondary Follicles

Are larger and possess a fluid-filled cavity called an antrum. The granulosa cells are still located in the inside of the basal lamina and the theca cells are on the periphery (outside of basal lamina).

Fallopian tubes (oviduct)

Are lined with simple ciliated columnar epithelium create a flow of peritoneal fluid into the uterine tubes to "pull" the ovulated ovum into the uterine tube and moves it toward the uterus. There are also non- ciliated cells dispersed throughout with secretory pegs. The epithelium covers a lamina propia, muscularis and serosa adventitia.

What phase do the oocytes halt once they're within the ovary?

At the first meiotic prophase

multilaminar primary follicle

Before reaching the secondary follicle, you go thru a multilaminar primary follicle when the granule cells thicken and form a multilaminar granulated layer with theca cells on the periphery. There is a basal lamina between theca cells and granulosa cell.

zona pellucida

Composed of three proteins that form a barrier around the oocyte. It is penetrated by thin processes of granulosa cells. There are gap junctions at the tips of these processes allow transfer of molecules to the oocyte from the granulosa cells.

plasminogen activator

Connections between granulosa cells weaken under the influence of plasminogen activator, which causes the follicle to rupture

Uterine contractility

Diminished by progesterone. Signals from mature fetus may stimulate uterine contractility during labor. Oxytocin also induces labor contractions of the uterus.

primary follicle

Egg & simple cuboidal cells + theca cells, granulosa cells, and zona pellucida.

uterine cycle

Estrogen and progesterone from the ovary target the endometrium (luminal wall) of the uterus causing it to grow and secrete uterine milk into the uterine lumen (exocrine).

How does levels of FSH and LH influence the ovarian cycle?

Every 28 days the pituitary hormones FSH and LH stimulate the growth of many follicles and maturation of one oocyte within the follicle called the ovarian cycle. The squamous layer thickens into cuboidal cells and becomes the primary follicle. The secondary follicle has an internal structure called the antrum. In the tertiary follicle the antrum has significantly enlarged. Then the ovulated oocyte is released at day 14 into the fallopian tube. The follicle persists as the corpus luteum which releases progesterone to maintain pregnancy. Then the corpus albicans remains for a few days and may leave a small amount of scar tissue.

cumulus oophorous

Expansions of the granulosa cells that surround the oocyte in the ovarian follicle and after ovulation.

The polar body results from what?

From an Unequal Division of the Oocyte Cytoplasm. The oocyte is then called a secondary oocyte.

Endometriosis

Growth of endometrial tissue outside of the uterus and breaks thru the myometrium and into the peritoneum.

Tertiary Follicle

Has an enlarged antrum that nearly completely fills the entire follicle.

Theca externa

Has more flattened cells that make smooth muscle and connective tissue

Endometrial glands (uterine glands)

Have simple columnar epithelia and possess a Nucleolar Channel System wherein membranes from the rough ER form tubules within the nucleus; this is a possible marker for endometrial receptivity for implantation of an embryo. Endometrial glands secrete proteases that may aid implantation, and which can degrade the zona pellucida. They secrete glycogen and oxytocin to induce labor

What are the three layers of the uterus?

Histologically the uterus can be divided into three layers: The endometrium has a simple columnar epithelia and loose CT containing many blood vessels (spiral arteries) and glands. The myometrium is a thick layer of smooth muscle which contracts during childbirth. The perimetrium is dense irregular connective tissue a part of the visceral peritoneum.

What happens prior to ovulation?

Immediately prior to ovulation the rise in estrogen secreted from the tertiary follicle causes LH to rise dramatically. The LH surge stimulates a rapid production of antral fluid which fills the follicle beyond capacity causing it to rupture. The ruptured follicle ejects the ovum (with a few layers of surrounding follicular cells called the corona radiata) into the fallopian tube.

Activating the oocyte receptor GPR3 does what?

Increases oocyte cAMP and causes suppression of meiosis.

What phase the oocyte is in prior to ovulation?

Meiosis at Prophase I due to some inhibitory influence of the granulosa cells.

Menstrual phase

Menstrual phase is 1-5 days: menstrual bleeding causes the endometrium to shed (decrease thickness); caused by the decrease in estrogen levels from the degeneration of the corpus luteum during the previous cycle. The spiral arteries contract leading to necrosis of the functional layer of the endometrium. The functional layer of the endometrium is shed during menstruation, but the basal layer is preserved.

atresia

Most oocytes do not undergo maturation and will degenerate. So only a few of the hundred thousand eggs will be matured.

Fertilization

Occurs in the oviduct. Fertilization is when a mature spermatozoon penetrates the zona pellucida to fuse with oocyte plasma membrane. This triggers the migration of so-called cortical granules towards the oocyte plasma membrane.

primordial ovarian follicle

Oocytes induce connective tissue cells to form a single layer around the oocyte and this is present at birth.


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