Activin A stimulates meiotic maturation of human oocytes and modulates granulosa cell steroidogenesis in vitro.

OBJECTIVE: To test the hypothesis that activin A promotes in vitro human oocyte meiotic maturation while inhibiting steroid secretion by nonluteinized antral granulosa cells. DESIGN: Prospective randomized controlled study. SETTING: A university medical center. PATIENT(S): Nine women ranging in age from 31-44 years who were undergoing oophorectomy for nonovarian pathology. INTERVENTION(S): Analysis of meiotic maturation of oocytes and steroid secretion by granulosa cells cultured in the presence or absence of activin A. MAIN OUTCOME MEASURE(S): Germinal vesicle breakdown (GVBD) and attainment of metaphase II (MII) in oocytes, and progesterone and E2 secretion by granulosa cells. RESULT(S): Activin A significantly enhanced GVBD (91% vs. 65%) for control and maturation to MII (56% vs. 35% for control) of immature oocytes. Activin A significantly suppressed basal, and inhibin A-and FSH-stimulated progesterone and E2 secretion by nonluteinized granulosa cells. CONCLUSION(S): Activin A is a promoter of oocyte maturation in vitro and a modulator of granulosa cell steroidogenesis in culture.

Pregnancy can be established in superovulated adult rats treated with progesterone and an aromatase inhibitor.

An adult superovulated rat model has been developed and is characterized by high ovulation rates, early morphological degeneration of embryos, complete embryo loss within 48 hours of conception and elevated peripheral estradiol(E2)/progesterone(P4) ratios. In this study, three trials were conducted using the superovulated adult rat model. First, control naturally cycling rats were compared with superovulated rats supplemented with 1 mg P4 on days 0-3 of pregnancy. A sperm positive vaginal smear is designated as day 0 of pregnancy. The P4 treated rats demonstrated improved embryo retrieval on day 1 of pregnancy, continued embryo recovery with a decrease in normal morphologic characteristics of integrity on day 2, with nearly total embryo loss by day 3. On each day, P4 levels were elevated 2-3 times over control. The second trial compared 3 groups of rats, 1) naturally cycling, 2) superovulated unsupplemented and 3) superovulated rats supplemented with 1 mg P4/rat/day and the aromatase inhibitor, 4-hydroxyandrostenedione (4-OHA), 12.5 mg/rat/day. The superovulated unsupplemented rats had no embryo recovery after day 2 of pregnancy, while the P4 and 4-OHA treated rats showed a variable ability to maintain normally developing embryos through day 4 of pregnancy. E2 levels were elevated in both superovulated groups on days 1-4 of pregnancy as were P4 levels on days 2-4. The E2/P4 ratio was significantly lowered only on day 1 of pregnancy in the P4 and 4-OHA treated group. The third trial demonstrated implantation in 50% of the superovulated rats supplemented with P4 and 4-OHA. In conclusion, implantation in the superovulated adult rats can occur with P4 and 4-OHA supplementation, however, this biologic phenomenon could not be explained by obvious changes in peripheral E2 and P4 levels.