Histology: Female Reproductive I and II Flashcards
(75 cards)
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Primordial Follicle
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- The oocyte is surrounded by a single layer of squamous epithelial cells, granulosa cells, which are separated from the surrounding stroma by a basement membrane.
- The oocyte is in first meiotic prophase (primary oocyte) and will remain in this phase until the time of ovulation.
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Each primary oocyte has a covering layer of [], derived from the []. They are a single layer of [] cells.
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Each primary oocyte has a covering layer of granulosa cells, derived from the germinal epithelium (mesothelium). they are a single layer of squamous epithelial cells.
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The primary oocyte plus its granulosa cell covering is called a [].
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The primary oocyte plus its granulosa cell covering is called a primordial follicle.
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Differences in Promordial Follicles and Pre-Antral Follices
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- Size
- Zona pellucida (apical)
- Granulosa cells becme cuboidal
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Pre-antral Follicle
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- The oocyte enlarges, accumulates nutrients and develops cortical granules.
- The granulosa cells become cuboidal to columnar; a thick glycoprotein layer, the zona pellucida, is produced jointly by the granulosa cells and the oocyte.
- Unilaminar pre-antral follicles have a single layer of granulosa cells; multilaminar pre-antral follicles have more than one layer of follicular cells;
- adjacent stromal cells begin to form a theca surrounding the granulosa cells, outside the basal lamina.
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Differences in Pre-antral Follicles and Antral Follicles
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- Size
- Antral cavities
- Theca interna (from stroma of ovary, very vascular)
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Antral Follicle
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- The primary oocyte attains full size (about 150µm).
- Small fluid-filled cavities, called antral cavities, appear among the granulosa cells.
- The theca develops further to form a distinct and very vascular theca interna and an outer theca externa, which blends with adjacent stroma.
- In response to LH the theca interna cells produce androgen which diffuses into the granulosa cell layer. In response to FSH granulosa cells synthesize the enzyme aromatase which converts the androgen into estrogen. Hence the follicle layers together function as an endocrine gland.
- As the follicle grows, the multiple antral cavities eventually fuse to form a single very large cavity.
- A mass of granulosa cells, the cumulus oophorus, surrounds the oocyte and forms a stalk by which the oocyte remains anchored to the wall of the follicle.
- The mature antral follicle, called a Graafian follicle, is huge, and bulges on the surface of the ovary and into the medulla.
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Estrogen Synthesis by Antral Follicles
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- Theca interna cells synthesize androgen in response to LH (pituitary)
- Androgen diffuses across basement membrane
- Granulosa cells synthesize aromatase (converts androgen to estrogen) in response to FSH (pituitary)
- Estrogen difuses into theca capillaries and enters general circulation
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The cumulus oophorus leaves the ovary with the oocyte during ovulation!
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Regulation of Follicular Maturation
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- Throughout the reproductive life of the female, a continuous supply of primordial follicles becomes active and develops into pre-antral follicles. This first stage in maturation is independent of gonadal hormone cycles.
- Each month during the reproductive life of the female, at approximately the beginning of the menstrual phase under the influence of rising FSH levels from the pituitary, a subset (about 20 or fewer, depending on the age of the female) of these preantral follicles is recruited and begins to develop into antral follicles.
- From among these maturing antral follicles, a single follicle is selected to be ovulated. It grows very rapidly and the estrogen it secretes produces a peak which stimulates a surge of LH from the pituitary.
- In the ovulatory follicle, also called a Graafian follicle, granulosa cells form a wall around a single large antral cavity, into which projects the primary oocyte surrounded by granulosa cells and attached via a stalk of granulosa cells to the follicle wall.
- The oocyte then responds to the LH surge by completing the 1st meiotic division and entering 2nd meiosis, stopping at metaphase. It’s now a secondary oocyte. The granulosa cells respond to LH by producing fluid as well as collagenase, and rupturing the follicle wall and the ovarian surface.
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Oral Contraceptive MOA
* Oral contraceptives containing estrogen inhibit both FSH and LH secretion thus blocking follicle maturation.
* In addition, progesterone in oral contraceptives promotes secretion of a cervical plug by cervical mucous glands (discussed with female reproductive tract).
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Atretic Follicle
* Only one oocyte per month is ovulated throughout the reproductive life of the female, which amounts to about 450 oocytes. The vast majority of oocytes and their follicles undergo apoptosis without ever fully maturing or ovulating.
* Follicles can begin to degenerate at any stage of development, and at any time prior to menopause. Once all follicles are lost either to atresia or ovulation, menopause occurs.
* Degenerating (= atretic) follicles are recognized histologically by the presence of a greatly thickened basal lamina, and cells with pyknotic nuclei.
* Eventually atretic follicles are completely resorbed into the ovarian stroma.
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Corpus Luteum
* The corpus luteum is an endocrine gland that develops in the ovary from the remains of the ruptured follicle, after the oocyte has been ovulated.
* The basal lamina separating the granulosa layer from the theca interna breaks down, and the granulosa layer is invaded by capillaries.
* Granulosa cells (now called granulosa lutein cells) and theca interna cells (now called theca lutein cells) secrete progesterone and estrogen (mainly progesterone).
* If there is no pregnancy, the corpus luteum degenerates after 12 days and leaves a scar, the corpus albicans.
* If there is a pregnancy, the corpus luteum grows and continues to function during the first trimester under the influence of hormones from the placenta; after the first trimester the corpus luteum of pregnancy degenerates to form a corpus albicans.
* Granulosa lutein cells look foamy - lipids and SER --\> synthesis of steroids by SER
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Corpus Albicans
* about 6 months to disappear if no pregnancy
* a preganacy formed corpus albicans is quite large and doesn't disappear over the life of a female
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Uterine Tube
* Four regions: the infundibulum, the ampulla, the isthmus, and the intramural segment.
* mucosa, musclaris, serosa
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Uterine Tube: Mucosa
* The uterine tube mucosa is highly folded, especially in the infundibulum and ampulla.
* The epithelium is simple columnar with two cell types: ciliated cells, with ciliary beat towards uterus; and secretory cells (peg cells), which produce nutritive medium as well as carbohydrates important in sperm capacitation, a process which alters the sperm membrane and behavior such that sperm become hyperactive and zona pellucida receptors are exposed.
Capacitation is necessary in order for sperm to be capable of fertilizing the oocyte.
• There is a loose connective tissue lamina propria which serves the epithelium.
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Uterine Tube: Muscularis
• The uterine tube has inner circular and outer longitudinal layers of smooth muscle. The thickness of the muscle layer increases towards the uterus.
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Uterine Tube: Serosa
•The uterine tube is covered by a serosa made of loose connective tissue covered by simple squamous epithelium. The serosa is very vascular, containing the anastomosing uterine and ovarian vessels. Most ectopic pregnancies occur in the uterine tube, where rupture causes life-threatening hemorrhage from these vessels.
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Changes in Sections of Uterine Tube
1. diameter
2. mucosa
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Uterine Blood Supply
•The uterus receives its blood supply through the uterine arteries; these give rise to arcuate arteries which run in the perimetrium, and in turn give rise to radial arteries; the radial arteries give off branches to supply the myometrium, then enter the endometrium, where they branch into straight arteries (to stratum basalis) and coiled arteries (to stratum functionalis).
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Perimetrium
• Depending on the region of the uterus, the perimetrium consists either of a serosa (loose connective tissue covered by simple squamous epithelium) or an adventitia.
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Myometrium
* This is a very thick layer of smooth muscle within which the fibers run approximately longitudinally in the outermost regions (nearest endometrium and perimetrium) and approximately circularly in the middle.
* In the non-pregnant woman, the muscle fibers are small; during pregnancy they undergo both hypertrophy and hyperplasia.
* The myometrium of the non-pregnant uterus undergoes constant rhythmic contractions; these are inhibited during pregnancy.
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Endometrium
* There are two levels recognized in the endometrium: the deeper level is the stratum basalis; the more superficial level is the stratum functionalis.
* In response to changes in circulating levels of estrogen and progesterone from the ovaries, the stratum functionalis is shed and regenerated every month.
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Menstrual Phase
* By definition, menstruation begins on day 1 of the menstrual cycle. It lasts until approximately day 5.
* During menstruation, the stratum functionalis degenerates and is shed. The stratum basalis is retained, and serves as a stem cell layer for later regeneration of the stratum functionalis.
* Anticoagulants permit some blood flow during shedding of the stratum functionalis, but constriction of coiled arteries and of radial arteries by the myometrium limits flow.
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Proliferative Phase
* The proliferative phase lasts from approximately day 5 through day 14.
* In response to increasing estrogen levels from developing ovarian follicles, stem cells in the stratum basalis undergo rapid proliferation: the straight tubular glands of the endometrium increase in length; at the same time, there is increased deposition of lamina propria and growth of the coiled arteries, such that the overall height of the endometrium more than doubles. Because of the rapid growth, epithelial cells pile up (nuclei are not in a single row) and mitotic figures are evident.
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Secretory Phase
* The secretory phase lasts from day 14 to day 28.
* Under the influence of progesterone from the corpus luteum, the endometrial glands become extensively coiled and the cells first sequester then secrete macromolecules which function in nutrition of the developing zygote.
* In the late secretory phase, in the absence of pregnancy, the stratum functionalis begins to deteriorate in response to decreasing levels of progesterone from the corpus luteum; the coiled arteries, which open and close rhythmically all the time, close for longer periods resulting in ischemia and shedding of the stratum functionalis.
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Cervix
* The cervix has a layer of smooth muscle continuous with the myometrium but much thinner.
* The mucosa of the cervix forms deep transverse folds, the plicae palmitae, into which open cervical mucous glands with simple columnar epithelium.
* The composition of cervical mucus varies: under the influence of progesterone, during the luteal phase of the menstrual cycle and during pregnancy, the mucus has low water content and is very viscous, forming a cervical plug which prevents entry of microorganisms (and sperm) into the uterus. At the time of ovulation, in response to high estrogen from the ovaries, cervical mucus becomes watery and allows passage of sperm. Progesterone-only birth control pills function mainly by promoting maintenance of the cervical mucous plug.
* There is an abrupt change from simple columnar to stratified squamous epithelium near the opening of the cervix into the vagina. The exact location of this squamocolumnar junction varies: at birth the junction is within the endocervical canal and is not visible on internal exam. After puberty and after the birth of a child, and even with use of oral contraceptives, there is a tendency for the junction to descend and become visible to the naked eye. With time, the exposed columnar epithelium undergoes squamous metaplasia, and the junction returns to a hidden position in the endocervical canal. The area of epithelium involved in metaplasia is known as the transformation zone.
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Significance of the Transformation Zone in Cervix
•The cervical transformation zone including the squamocolumnar junction is the area where most cervical cancers arise. It is this area that is sampled when a Pap smear is taken.
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Vagina
* The vagina is covered by an adventitia of loose connective tissue.
* The muscularis is poorly developed; it is made up of outer longitudinal and inner circular muscle.
* The mucosa is lined with stratified squamous epithelium; under the influence of estrogen the epithelial cells synthesize glycogen; when the cells are sloughed, the glycogen is fermented to lactic acid by commensal bacteria in the vaginal lumen; the low pH which results protects against some pathogenic microorganisms.
* The lamina propria of the mucosa is made up of dense elastic connective tissue and contains a well developed plexus of venules. These become leaky during sexual arousal, and the leaked fluid enters the vaginal lumen.
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Vaginal Mucosa Antibacterial Properties
•The mucosa is lined with stratified squamous epithelium; under the influence of estrogen the epithelial cells synthesize glycogen; when the cells are sloughed, the glycogen is fermented to lactic acid by commensal bacteria in the vaginal lumen; the low pH which results protects against some pathogenic microorganisms.
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External Genitalia
* The vagina opens into the vestibule, defined by the labia minora on either side; outside the labia minora are the labia majora; anterior to the urethral meatus is the clitoris.
* The clitoris is a homologue of the penis and has a similar structure, in that it also contains erectile tissue equivalent to the corpora cavernosa in the male. Unlike in the penis, the clitoris lacks a corpus spongiosum, and the urethra opens independently of the clitoris.
* All of the vestibular area is covered by stratified squamous epithelium and is lubricated by mucous glands; the major vestibular glands (Bartholin’s glands, homologues of bulbourethral glands of male) open into the vestibule near the vaginal opening.
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Mammary Gland
* Mammary glands are compound tubuloalveolar glands.
* Each gland consists of 15-25 independent lobes, each divided into lobules, and each with its own lactiferous duct which opens on the nipple.
* Lobes are separated by connective tissue septa and contain mainly adipose tissue.
* Ducts are present within the septa; secretory endpieces (alveoli) are poorly developed in non-lactating mammary gland.
* During pregnancy, the duct system becomes more extensive and secretory endpieces develop under the influence of estrogen, progesterone and other hormones.
* The secretory cells produce milk proteins, including lactalbumin, lactoglobulin and casein, as well as lipids. They also transport lactose (synthesized from glucose and galactose), salts, water, and IgA and IgM antibodies (via poly-Ig receptor mediated transepithelial transport).
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