Menstrual cycle Physiology

Dr. Atef Abood

Ovaries
Primordial follicle one layer of squamouslike follicle cells surrounds the oocyte Primary follicle two or more layers of cuboidal granulosa cells enclose the oocyte Secondary follicle has a fluid-filled space between granulosa cells that coalesces to form a central antrum Graafian follicle secondary follicle at its most mature stage that bulges from the surface of the ovary Ovulation ejection of the oocyte from the ripening follicle Corpus luteum ruptured follicle after ovulation 2

Oogenesis
At puberty, one activated primary oocyte produces two haploid cells
The first polar body The secondary oocyte

The secondary oocyte arrests in metaphase II and is ovulated If penetrated by sperm the second oocyte completes meiosis II, yielding:
One large ovum (the functional gamete) A tiny second polar body
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Ovarian Cycle
Monthly series of events associated with the maturation of an egg Follicular phase period of follicle growth (days 114) Luteal phase period of corpus luteum activity (days 1428) Ovulation occurs midcycle

Follicular Phase
This phase is under the effect of FSH and to a little extent LH. It starts by activation of several; primordial follicles. At the 6th day only one follicle starts to grow rapidly becoming a dominant follicle called the Graffian follicle while the others regress. The primordial follicle, directed by the oocyte, becomes a primary follicle Primary follicle becomes a secondary follicle
The theca folliculi and granulosa cells cooperate to produce estrogens The zona pellucida forms around the oocyte The antrum is formed

Follicular Phase (Cont.)

The secondary follicle becomes a vesicular follicle
The antrum expands and isolates the oocyte and the corona radiata The full size follicle (vesicular follicle) bulges from the external surface of the ovary The primary oocyte completes meiosis I, and the stage is set for ovulation

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Ovulation
Ovulation occurs when the ovary wall ruptures and expels the secondary oocyte Mittelschmerz a twinge of pain sometimes felt at ovulation 1-2% of ovulations release more than one secondary oocyte, which if fertilized, results in twins

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Luteal Phase
After ovulation, the ruptured follicle collapses, granulosa cells enlarge, and along with internal thecal cells, form the corpus luteum The corpus luteum secretes progesterone and estrogen If pregnancy does not occur, the corpus luteum degenerates in 10 days, leaving a scar (corpus albicans) If pregnancy does occur, the corpus luteum produces hormones until the placenta takes over that role (at about 3 months)
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Uterine (Menstrual) Cycle

Series of cyclic changes that the uterine endometrium goes through each month in response to ovarian hormones in the blood : Menstrual phase Days 1-5
uterus sheds all but the deepest part of the endometrium

Days 6-14: Proliferative (preovulatory) phase endometrium rebuilds itself Days 15-28: Secretory (postovulatory) phase endometrium prepares for implantation of the embryo

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Endometrium
Has numerous uterine glands that change in length as the endometrial thickness changes Stratum functionalis:
Undergoes cyclic changes in response to ovarian hormones Is shed during menstruation

Stratum basalis:
Forms a new functionalis after menstruation ends

Does not respond to ovarian hormones

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Proliferative phase
Duration: 2 weeks Thickness: 0.5mm 5mm Under the influence of estrogens from the developing follicle, the endometrium increases rapidly in thickness from the fifth to the fourteenth days of the menstrual cycle. As the thickness increases, the uterine glands are drawn out so that they lengthen, but they do not become convoluted or secrete to any degree. These endometrial changes are also called the preovulatory or follicular phase of the cycle.
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Secretory phase
Duration: 2 weeks Thickness: 5-6mm After ovulation, the endometrium becomes more highly vascularized and slightly edematous under the influence of estrogen and progesterone from the corpus luteum. The glands become coiled and tortuous, and they begin to secrete a clear fluid. Consequently, this phase of the cycle is called the secretory or luteal phase. Late in the luteal phase, the endometrium, like the anterior pituitary, produces prolactin, but the function of this endometrial prolactin is unknown.
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Menses
If fertilization does not occur, progesterone levels fall, depriving the endometrium of hormonal support Spiral arteries kink and go into spasms and endometrial cells begin to die The functional layer begins to digest itself Spiral arteries constrict one final time then suddenly relax and open wide The rush of blood fragments weakened capillary beds and the functional layer sloughs Nonclotting menstrual blood mainly comes from artery (75%) Interval: 24-35 days (28 days). duration: 2-6 days. the first day of menstrual bleeding is consideredy by day 1 Shedding: 30-50 ml
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Menstruation
Menstrual blood composition is predominantly arterial, with only 25% of the blood being of venous origin. It contains tissue debris, prostaglandins, and relatively large amounts of fibrinolysin from endometrial tissue. The fibrinolysin lyses clot, so that menstrual blood does not normally contain clots unless the flow is excessive. The usual duration: 3-5 days, but flows as short as 1 day and as long as 8 days can occur in normal women.

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Menstruation
The amount of blood lost may range normally slight spotting to 80 mL; the average amount lost is 30 mL. Loss of more than 80 mL is abnormal. Obviously, The amount of flow can be affected by various factors, including the thickness of the endometrium, medication, and diseases that affect the clotting mechanism. After menstruation, a new endometfrom rium regenerates from the stratum basale.
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Menses (Cont.)
When the corpus luteum regresses, hormonal support for the endometrium is withdrawn. The endometrium becomes thinner, which adds to the coiling of the spiral arteries. Foci of necrosis appear in the endometrium, and these coalesce. There is in addition spasm and then necrosis of the walls of the spiral arteries, leading to spotty hemorrhages that become confluent and produce the menstrual flow.

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Menses (Cont.)
The vasospasm is probably produced by locally released prostaglandins. There are large quantities of prostaglandins in the secretory endometrium and in menstrual blood, and infusions of PGF2 produce endometrial necrosis and bleeding. One theory of the onset of menstruation holds that in necrotic endometrial cells, lysosomal membranes break down, with the release of enzymes that foster the formation of prostaglandins from cellular phospholipids.
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Changes of other genital organs

Cervix During follicular phase estrogen causes mucus to be thin,clear, watery and the the midcycle a drop can be stretched into a long, thin thread that may be 8-12 cm or more in length. In addition, it dries in an arborizing, fern-like pattern During luteal phase progesterone causes mucus to be thick, opaque, tenacious and cellular and loss of ability to form fern like appearance.
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Changes of other genital organs

Cyclic changes in the vagina
Under the influence of estrogens, the vaginal epithelium becomes cornified, Under the influence of progesterone, a thick mucus is secreted, and the epithelium proliferates and becomes infiltrated with leukocytes.

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Changes of other genital organs

Cyclic changes in the breast
Estrogens cause proliferation of mammary ducts. progesterone causes growth of lobules and alveoli. The breast swelling, tenderness, and pain experienced by many women during the 10 days preceding menstruation are probably due to distention of the ducts, hyperemia, and edema of the interstitial tissue of the breast. All these changes regress, along with the symptoms, during menstruation.
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Establishing the Ovarian Cycle

During childhood, ovaries grow and secrete small amounts of estrogens that inhibit the hypothalamic release of GnRH As puberty nears, GnRH is released; FSH and LH are released by the pituitary, which act on the ovaries These events continue until an adult cyclic pattern is achieved and menarche occurs
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Hormonal Interactions During the Ovarian Cycle

Day 1 GnRH stimulates the release of FSH and LH FSH and LH stimulate follicle growth and maturation, and lowlevel estrogen release Rising estrogen levels:
Inhibit the release of FSH and LH

Estrogen levels increase and high estrogen levels have a positive feedback effect on the pituitary, causing a sudden surge of LH The LH spike stimulates the primary oocyte to complete meiosis I, and the secondary oocyte continues on to metaphase II

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Hormonal Interactions During the Ovarian Cycle

Day 14 LH triggers ovulation LH transforms the ruptured follicle into a corpus luteum, which produces inhibin, progesterone, and estrogen These hormones shut off FSH and LH release and declining LH ends luteal activity Days 26-28 decline of the ovarian hormones Ends the blockade of FSH and LH The cycle starts anew
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Summary of hormonal control of the cycle

In an important sense, regression of the corpus luteum (luteolysis) starting 3-4 days before menses is the key to the menstrual cycle. PGF2 appears to be a physiologic luteolysin, but this prostaglandin is only active when endothelial cells producing ET-1 are present. Therefore it appears that at least in some species luteolysis is produced by the combined action of PGF2 and ET-1. In some domestic animals, oxytocin secreted by the corpus luteum appears to exert a local luteolytic effect, possibly by causing the release of prostaglandins. Once luteolysis begins, the estrogen and progesterone levels fall and the secretion of FSH and LH increases. A new crop of follicles develops to start a new cycle
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Menstrual Abnormalities
Anovulatory cycle Amenorrhea
Primary amenorrhea: period never occurs Secondary amenorrhea stop of the cycle after normal periods have occurred.

Menorrahgia: excessive bleeding during menstruation Hypomenorrhea: scanty or little bleeding Metrorrahgia: bleeding between cycles. Oligomenorrhea: reduced frequency of the periods.
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