Ans. A. Subnuclear vacuolation. (Ref. Williams9 Gync lst/Fig,15-20; Obstetrics Dutta 7th/pg. 17-18).The endometrial cycle follows the changes in the endometrium during the 'menstrual' cycle. It is divided into phases with characteristic histological changes:# Proliferative phase (pre-ovulatory) - can be though of as building the endometrium at the same time as the follicle is maturing for ovulation (need to grow before it can secrete)# Interval phase# Secretory (post-ovulatory)- can be thought of as preparing for implantation (secretory in order to support implantation)# Menstrual phaseProliferative PhaseThe glands are simple. Mitotic activity is conspicuous. In the endometrium, the proliferative activity occurs even before the complete cessation of menstruation, i.e. a few days into the cycle. The glands at this earlier stage are relatively straight or at most slightly coiled and are found within relatively loose endometrial stroma. There is brisk cell division with prominent mitotic activity in both the glands and the stroma. Under the influence of oestrogen, the stroma is often the thickest at day 10. After this, the rate of glandular growth relative to the stroma results in coiling of the glands as the cycle moves towards ovulation. The nuclei rather than central are pseudostratified, though they tend to be found in the basal half.Interval PhaseThe interval phase occurs over a short period of 24-48 hours. 1-2 days folllowing ovulation, there is peak of luteinizing hormone and increased progesterone, which brings on the secretory changes. The early interval phase is therefore indistinguishable from late proliferative phase without biochemical corrobation. The cut-off is somewhat arbitrary, but there may be a brief overlap of proliferative and secretory phase features, the latter manifest as subnuclear vacuolation.Secretory PhaseThe amount of subnuclear vacuolation is at its maximum in the early secretory phase (days 3-4 post-ovulation or days 17- 18 of the cycle) and are initially seen to line up giving the appearence of a line of vacuoles and a line nuclei. Mitotic activity is minimal as the glands are no longer dividing, but the cells dilate and become more tortuous. As the cycle moves into the mid-secretory phase, the vacuoles begin to be found above the nuclei as they head for the luminal surface.# Early secretory phase change. There are subnuclear vacuoles. The glands are beginning to become convoluted. Mitotic activity is now absent.# In the mid-secretory phase (days 5-11 post-ovulation or days 19-25 of the cycle), the glands remain dilated, but become more irregular with a papillary or saw-tooth appearence. The vacuoles move to a supranuclear position and the contents may be seen within the lumina. The stroma becomes looser and more oedematous, becoming most prominent at days 20-22. Day 21 is regarded as the optimal time for implantation. Decidualisation of the stroma also occurs.# In the late secretory phase (days 26-28), decidualisation extends from the surface to the deeper stroma. Lymphocytes being to appear.Menstrual PhaseIn the absence of conception, hCG is not produced and corpus luteum is unable to sustain itself. Withdrawal of progesterone causes the stroma to crumble, forming balls of deep blue stromal cells (with H&E staining). Secretions are also exhausted at this stage and the glands break off. Red blood cells and neutrophils are mixed between the involuting structures.OVULATIONDefinition: It is a process whereby a secondary oocyte is released form the ovary following the rupture of graafian follicle and becomes available for the conception.Mechanism: A. Changes in the follicle:a. Preovulatory enelargement of the Graafian follicle due to accumulation of follicular fluid and measures 20 mm in diameter.b. The cumulus oophorus separates separates from the rest of granulosa cells and floats freely in the antrum. The inner layer of cells surrounding the oocyte is arranged radially and is termed corona radiata. The stigma develops as a conical projection, which penetrates the outer surface layer of ovary. The cumulus escapes out of the follicle as a slow oozing process, taking about 1-2 minutes along with varying amount of follicular fluid.c. Changes in the oocyte: Prior to ovulation its cytoplasmic volume is increased along with chnages in the number and distribution of mitochondria and in the golgi apparatus. Completion of arrested first meiotic division occurs with extrusion of the fitrst polar body, each containing haploid number of chromosomes.Causes:# LH surge: Sustained peak level of estrogen for 24-36 hrs in the late follicular phase -LH surge occurs form anterior pituitary (persists for 24 hrs) - Ovulation occurs approx 24-36 hrs after LH surge ->LH surge stimulates completion of reducation division of the oocyte -^initiate leutinisation, synthesis of progesterone and pgs. IT IS THE BEST PREDICTOR OF OVULATION.# FSH rise: Preovulatory rise of progesterone facilitates the positive feedback action of estrogen to induce FSH surge a increase in plaminogen activator a plasminogen a plasmin a helps lysis of the walls of follicle. Thus, the combined LH/FSH midcycle surge is responsible for the final tage of maturation, rupture of the follicle, and expulsion of the oocyte.# Stretching factor# Contraction of micromuscles in the theca externa and ovarian stroma due to increased pg synthesis.