•Fig. 44.21 Ovulation.GVBD,germinalvesiclebreakdown.(ModifiedfromWhiteBA,PorterfieldSP.Endocrine Physiology. 4thed.Philadel-phia:Mosby;2013.)Surface epithelium Tunica albugineaLuteinizing theca Blood vessels invading granulosa Luteinizing mural granulosa without basal lamina Peritoneal cavity Ruptured antrum Expanded cumulus Zona pellucida First polar body 2° oocyte after GVDB 2.
The attachment of the cumulus cells to the mural granulosa cells degenerates, and the cumulus-oocyte complex becomes free-floating within the antral cavity (see
Fig. 44.21 ). Cumulus cells also respond to the LH surge by secreting hyaluronic acid and other extracellular matrix components. These substances enlarge the entire cumulus-oocyte complex, a process called cumulus expansion (see
Fig. 44.21 ). This enlarged cumulusoocyte complex is more easily captured and transported by the oviduct. The expanded cumulus also makes the cumulus-oocyte complex easier for spermatozoa to find. Sperm express a membrane hyaluronidase that allows them to penetrate the expanded cumulus. The cumulusoocyte complex is released through the ruptured stigma through a relatively slow process.
3.
The basal lamina of mural granulosa cells is broken down so that blood vessels and outer-lying theca cells can push into the granulosa cells. Granulosa cells secrete angiogenic factors such as vascular endothelial growth factor (VEGF), angiopoietin 2, and basic fibroblast growth factor (bFGF), which significantly increase the blood supply to the new corpus luteum.
The Gamete
Before ovulation the primary oocyte is competent to complete meiosis, but it is arrested in prophase I (see
Fig.
44.18 ). The LH surge inhibits production of cGMP by granulosa and cumulus cells, thereby removing inhibition of the oocyte-specific PDE3A. PDE3A proceeds to degrade cAMP to inactive AMP, thereby removing the brake on meiotic progression. The oocyte then progresses to meta-phase II and subsequently arrests at metaphase II until fertilization.
Both theca and mural granulosa cells express LH receptors at the time of the LH surge. The LH surge induces differentiation of the granulosa cells—a process that continues for several days after ovulation. During the periovulatory period, the LH surge induces the following shifts in steroidogenic activity of the mural granulosa cells (now turning into granulosa lutein cells).
1.
Transient inhibition of CYP19 expression and consequently estrogen production. The rapid decline in estrogen helps turn off the positive feedback on LH secretion.
2.
Breakdown of the basal lamina and vascularization of the granulosa cells. This makes LDL and HDL cholesterol accessible to these cells for steroidogenesis. The LH surge also increases expression of the LDL receptor and HDL receptor (SR-BI) in granulosa cells.
3.
Onset of expression of StAR protein, CYP11A1 (side chain cleavage enzyme), and 3β-HSD (
Fig. 44.22 ). Expression of these enzymes are key to the onset of production of high levels of progesterone by these cells. As discussed later, high progesterone synthesis is absolutely necessary for maintenance of pregnancy. Because CYP17 activity, especially its 17,20-lyase function, is largely absent in granulosa lutein cells, progesterone is not further metabolized to another steroid but instead exits the cells and enters the circulation.