HUMAN CHORIONIC-GONADOTROPIN OR HUMAN RECOMBINANT FOLLICLE-STIMULATING-HORMONE (FSH)-INDUCED OVULATION AND SUBSEQUENT FERTILIZATION AND EARLY EMBRYO DEVELOPMENT IN HYPOPHYSECTOMIZED FSH-PRIMED MICE

Adult hypophysectomized FSH-primed mice were used to study ovulation, fertilization, and preimplantation embryo development. Twelve days aft er hypophysectomy, animals were injected sc with oFSH (4 Ag/day) twice a day for 3 days. This resulted in large preovulatory follicles that did not secrete estrogen. Concurrent with the last FSH injection, eith er hCG (5 IU) or human recombinant FSH (10 IU) was injected sc to indu ce ovulation. Animals were mated or not and killed 1-4 days later. The ovulation rate was similar for both the hCG-induced group (FH) and th e FSH-induced group (FF), 97% and 90%, respectively. About 45% of the FH mice mated successfully with 56% of the eggs fertilized compared to only 25% of the FF mice with 45% of the eggs fertilized. However, onl y 5% of ovulated eggs developed to four-cell stages in vivo by day 3 f or the FH animals and none in the FF group. To determine the reasons f or the in vivo retarded embryo development, embryos at the one- or two -cell stage were collected on day 2 from the FH group. After 96 h of c ulture, 22% of two-cell embryos were converted to blastocysts, and 11% of one-cell eggs divided to the four-cell stage. In contrast, 80% of two-cell embryos from normal mice develop into blastocysts by 72 h of culture. The ovarian incubation medium and serum were used to measure progesterone (P4), androstenedione (A), and estradiol (E2). The patter ns of serum and in vitro production of steroids were parallel. In FH m ice, P4 increased immediately on the day after hCG injection (day 1) a nd decreased progressively on days 2 and 3; A and E2 levels increased on day 2, A decreased on day 3, and E2 decreased on day 4. When human recombinant FSH was used to induce ovulation, there were no significan t changes in serum P4 and A; E2 levels were about 4 times higher on da y 1 than in the FSH-primed control, then dropped to baseline levels on days 2 and 3. However, on day 3 in both the FH and FF groups, FSH rec eptors were still present on the granulosa cells of antral follicles, and LH/hCG receptors were present on the granulosa cells of large antr al follicles and newly formed corpora lutea. These results demonstrate that preovulatory follicles induced by FSH alone, without previous es trogen secretion, could be induced to superovulate, but the quality of the oocytes and the abnormal hormonal environment are responsible for retarded development of preimplantation embryos in vivo and in vitro.