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Biology of Reproduction, Vol 25, 261-271, Copyright © 1981 by Society for the Study of Reproduction
1 MRC Group in Reproductive Biology,
Department of Obstetrics and Gynaecology and Department of Physiology,
The University of Western Ontario,
London, Ontario, Canada N6A 5A5 Reduced fertility is frequently associated with excessive follicle stimulation following the use of
exogenous gonadotropins to induce ovulation. To investigate the mechanisms involved, a superovulatory dose of pregnant mare serum gonadotropin (PMSG, 40 IU) was administered to seventysix 30-day-old rats (0800-0900 h, Day 0). Sixty-eight control rats received 4 IU, a dose which
induces normal numbers of ovulations followed by normal pregnancy. Some rats were killed at
Mating and fertilization occurred in most superovulated and control rats. Mean numbers of CL
observed in control rats killed on Days 2, 3, 4, 5, and 7 were 0, 10.7, 10.5, 11.6, and 11.5, respectively. The corresponding means for CL plus luteinized follicles in superovulated rats were 55, 65,
85, 85, and 112, respectively. Ovaries from superovulated rats also contained, on average, 20.8,
27.5, 18.5, 13.6, and 12.3 large, nonluteinized follicles on Days 2, 3, 4, 5, and 7, respectively; 10.4
such follicles were observed in controls on Day 2 only. Mean numbers of ova or embryos recovered
on Days 2, 3, 4, 5, and 7, respectively, from oviducts of controls were 0, 8.3 (1-cell embryos), 8.7
(2-cell embryos), 8.9 (2-, 3-, and 4-cell embryos), and 0, and from the oviducts of superovulated
rats, 15.1 (unfertilized ova), 38.4 (1-cell embryos plus degenerate ova), 17.9 (2-cell embryos plus
degenerate ova), 6.6 ( 2-, 3-, and 4-cell embryos plus degenerate ova), and 0. Flushings of uteri
yielded 9.4 blastocysts from controls on Day 7 only, and only an occasional embryo from superovulated rats on Days 4 and 5, but none on Day 7. Superovulated rats ovulated over a prolonged
period, presumably on the nights of Days 1 and 2. Mean serum estradiol levels (pg/ml ± SEM)
observed in control and superovulated rats on Days 2, 3, 4, 5, and 7, respectively, were 93 ± 5 vs
230 ± 10, 34 ± 3 vs 134 ± 19, 31 ± 2 vs 201 ± 33, 34 ± 2 vs 98 ± 10, and 37 ± 3 vs 49 ± 3. The
corresponding serum progesterone levels (ng/ml ± SEM) were 2 ± 1 vs 29 ± 3, 9 ± 3 vs 74 ± 5, 22 ±
3 vs 152 ± 11, 43 ± 3 vs 200 ± 15, and 61 ± 4 vs 220 ± 18. respectively. The results suggest that
embryo loss following superovulation is due to excessive estrogenic stimulation of the genital tract,
probably arising from large follicles which persist after normal ovulation occurs.
1200 h on Day 2. The remainder were caged with mature fertile males on Day 2, scored for the
occurrence of mating on the morning of Day 3, and killed at about 1200 h on Days 3, 4, 5, or 7
(Days 1, 2, 3, or 5 of pregnancy, respectively). Corpora lutea (CL) and large, nonluteinized follicles
were counted, and oviducts and uteri flushed to determine number, location, and stage of development of embryos. Ovarian and uterine weight, the accumulation of fluid in the uterus and ampulla,
the ovarian content of estradiol, and serum levels of estradiol and progesterone were also recorded.
Note:
ACKNOWLEDGMENTS
We thank Ms. Joan Calaresu, Ms. Mira Dobias, and
Mr. Gerald Barbe for their excellent technical assistance and Dr. T. G. Kennedy for many helpful discussions during the course of these studies.
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