OB - Ovarian and Endometrial Cycle

THE OVARIAN CYCLE The development of predictable, regular, cyclical and spontaneous ovulatory menstrual menstrual cycles is regulated by complex interactions of the hypothalamic-pituitary axis, the ovaries and the genital tract Average duration of the menstrual cycle: 28 days.

FOLLICULAR (PREOVULATORY) OVARIAN PHASE

STAGES OF HUMAN FOLLICULAR DEVELOPMENT Gonadotropin – independent independent recruitment recruitment of primordial follicles starts from the resting pool to growth towards the o antral stage under the control of growth differentiation factors 9 o & 10, produced by the oocytes, which regulate the proliferation and differentiation of the granulosa cells as the primary follicles grow

Follicular phase

2-GONADOTROPIN, 2-GONADOTROPIN, 2-CELL HYPOTHESIS granulose cell  –  FSH  FSH thecal cell  –  LH  LH FSH induces the enzyme aromatase and expansion of the antrum of the growing follicles The follicle within the cohort that is most responsive to FSH is likely to be the fi rst to produce estradiol and initiate expression of LH receptors After the appearance of LH receptors The preovulatory granulosa cells begin to secrete o small quantities of progesterone which exert positive feedback on the estrogen-primed pituitary to cause release of LH LH stimulates thecal cell production production of o androstenedione During the early follicular phase inhibin B produced by granulosa cells o negative feedback to the pituitary to inhibit FSH o release resulting to non-development of other follicles enabling only 1 follicle to reach maturity

Gonadotropin-dependent growth of antral follicles involves FSH o enables a group of antral follicles (cohort) to begin a o phase of semisynchronus growth only the follicles progressing to this s tage develop o the capacity to produce estrogen Follicular Phase estrogen levels rise in parallel to the growth of the o dominant follicle and the increase in its number of granulose cells which are the exclusive site of FSH receptor expression increase in FSH in the late luteal phase of the o previous cycle stimulates an increase in FSH receptors  enable aromatization aromatization of the thecal cell  derived androstenedione androstenedione into estradiol

Luteal (Postovulatory) Phase Corpus luteum develops and the lifespan is o maintained by low-frequency, high amplitude pulses of LH s ecreted by gonadotropes in the anterior pituitary Estrogen, just after ovulation, decrease followed by o a secondary rise at midluteal phase Estrogen undergoes secondary decrease in estradiol o production toward the end of the luteal phase Progesterone production peaks during the midluteal o phase Human Corpus Luteum A transient endocrine organ that rapidly regresses o 9  – 11 11 days after ovulation Luteolysis results from the combination of decreased o levels of circulating LH in the late luteal phase and decreased LH sensitivity of luteal cells Luteolysis, characterized by the dramatic drop in o circulating levels of estradiol and progesterone, is critical to allow the follicular development and ovulation of the next ovarian cycle

OB 3A: Ovarian and Endometrial Cycle - richuy

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It also signals the endometrium to initiate the molecular events that will lead to menstruation

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In Arey's analysis of 5322 cycles in 485 normal women, an average interval of 28.4 days was estimated; his finding for the average cycle length in pubertal girls was longer, 33.9 days.

THE ENDOMETRIAL CYCLE PROLIFERATIVE PHASE EARLY PROLIFERATIVE PHASE:  

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the endometrium is thin, usually less than 2 mm in thickness The glands at this stage are narrow, tubular structures that pursue almost a straight and parallel course from the basal layer toward the surface of the endometrial cavity Mitotic figures, especially in the glandular epithelium, are identified by the fifth cycle day, and mitotic activity in both epithelium and stroma persists until day 16 to 17 (2 to 3 days after ovulation). there is no extravascular blood or leukocyte infiltration in the endometrium at this stage.

EVENTS THAT OCCURS DURING MENSES: The resultant stasis is the primary cause of endometrial ischemia and then tissue degeneration. A period of vasoconstriction precedes the onset of menstruation and is the most striking and constant event observed in the menstrual cycle. 

ACTION OF PROSTAGLANDINS DURING MENSES: 

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LATE PROLIFERATIVE PHASE: 

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the endometrium thickens, the result of both glandular hyperplasia and an increase in stromal ground s ubstance (edema and proteinaceous material). loose stroma is especially prominent, and the glands in the superficial portions of the e ndometrium (the functionalis layer) are widely separated compared with those of the deeper zone (the basalis layer), where the glands are more crowded and the stroma is denser surface epithelial cells acquire numerous microvilli, which increase epithelial surface area, and cilia, which aid in the movement of endometrial secretions in the secretory phase

SECRETORY PHASE EARLY SECRETORY PHASE:

A role for prostaglandins, especially prostaglandin F2 (PGF2), which is a vasoconstrictor, in the initiation of menstruation The administration of PGF2 to women gives rise to symptoms that mimic dysmenorrhea, which is commonly associated with normal menses and likely is caused by myometrial contractions and uterine ischemia. administration of PGF 2 to nonpregnant women also will cause menstruation

ACTION OF PRSTAGLANDINS regulate spiral artery blood flow. Endothelin-1 (ET-1) is a potent vasoconstrictor that was first identified as a product of vascular endothelial cells  

DECIDUA OF THE ENDOMETRIUM Highly modified endometrium of pregnancy Decidualization –  dependent on estrogen and progesterone and factors secreted by the implanting blastocyst during trophoblast invasion  

DECIDUAL STRUCTURES Decidua basalis  –  directly beneath the site of blastocyst implantation Decidua capsularis overlying the enlarging blastocyst, separating it from the rest of the uterine cavity prominent on the 2nd month of pregnancy covered with single layer of flattened epithelial cells w/o glands Internally, avascular extraembryonic fetal membrane  –   Chorion Laeve Decidua Parietalis remainder of uterus If fused with capsularis, Decidua Vera (14-16 weeks) 

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the dating of the endometrium is based on the histology of the glandular epithelium

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By day 17, glycogen accumulates in the basal portion of the glandular epithelium, creating subnuclear vacuoles and pseudostratification- FIRST SIGN OF OVULATION.

MID TO LATE SECRETORY ENDOMETRIUM:

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relies on changes seen in the endometrial stroma On cycle days 21 to 24, the stroma becomes edematous. On days 22 to 25, stromal cells surrounding the spiral arterioles begin to enlarge, and stromal mitosis becomes apparent An important characteristic of the secretory-phase endometrium occurring between days 22 and 25 is the striking change associated with the predecidual transformation of the upper two thirds of the functionalis layer. The glands exhibit extensive coiling and secretions become visible within the lumen

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PREMENSTRUAL PHASE the infiltration of the stroma by polymorphonuclear leukocytes, giving a pseudoinflammatory appearance to the tissue 

MENSTRUAL PHASE: As the regression of the endometrium occurs, the coiling of the spiral arteries becomes sufficiently severe that the resistance to blood flow in these vessels is increased strikingly, causing hypoxia of the endometrium. vasoconstriction precedes the onset of menstruation 

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MENSTRUATION Origin Menstrual bleeding is of both arterial and venous origin, but arterial bleeding is, quantitatively, appreciably greater than venous Endometrial bleeding appears to begin by rupture of an arteriole of a coiled artery, with consequent formation of a hematoma. 

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3 LAYERS OF DECIDUA PARIETALIS AND BASALIS 3 layers: zona compacta zona functionalis zona spongiosa zona basalis  –   gives rise to new endometrium after delivery 

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Interval During Menses modal interval at which menstruation recurs is considered to be 28 days average adult women, one third of menstrual cycles departed by more than 2 days from the mean of the lengths of all cycles.

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DECIDUAL REACTION Completed only with blastocyst implantation Endometrial stromal cells enlarge to form polygonal or round decidual cells Nuclei  –  round and vesicular Cytoplasm-clear slightly basophilic, surrounded by translucent membrane Decidual cells  –  lined by pericellular membranes  

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DECIDUAL BLOOD SUPPLY Capsularis –  lost as the embryo-fetus grows Parietalis –  through spiral arteries persists Spiral arterioles or arteries  –  invaded by the cytotrophoblasts  –  walls of the vessels in the basalis are destroyed  not responsive to vasoactive agents Fetal chorionic vessels  –  responsive to to vasoactive agents   

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DECIDUAL HISTOLOGY NITABUCH LAYER-zone of fibroid degeneration if defective  –  Placenta accreta 

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DECIDUAL PROLACTIN PRODUCTION hPL  –  placental lactogen, produced by syncitiotrophoblast Prolactin  –  product of the same gene that encodes for Prolactin secreted by the anterior pituitary Prolactin 10,000 ng/mL - in the amniotic fluid, during the 20th24th week 250 ng/mL - in the fetus 150-200 ng/mL - in maternal plasma Arachidonic acid  –  attenuates rate of Prolactin secretion ET-1, IL-1, IL-2 and Epidermal Growth Factor  –  decreases Prolactin secretion ROLE: 1.) regulating Immunological functions in the tissue during pregnancy 2.) Regulation of angiogenesis that occur during implantation  

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OB 3A: Ovarian and Endometrial Cycle - richuy

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