Biol Reprod Keystone Symposia Conference on Frontiers in Reproductive Biology & Regulation of Fertility.
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Biology of Reproduction, Vol 25, 253-260, Copyright © 1981 by Society for the Study of Reproduction

Superovulatory Doses of Pregnant Mare Serum Gonadotropin Cause Delayed Implantation and Infertility in Immature Rats

B. G. MILLER 1, and D. T. ARMSTRONG 1

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


Immature Sprague-Dawley rats were maintained with lights off between 1900 and 0500 h and treated with pregnant mare serum gonadotropin (PMSG) at 30 days of age (0800-0900 h, Day 0). One hundred and ninety-eight animals were caged individually with mature fertile males at 1500 h on Day 2, scored for the occurrence of mating on the morning of Day 3, and killed on Day 22. Rats received 4, 8, 16, or 40 IU PMSG; a high proportion of those receiving each dose mated. Of those which mated, almost all receiving 4 or 8 IU, 76% of those receiving 16 IU, and none receiving 40 IU were pregnant on Day 22. The mean numbers of live fetuses in pregnant rats that received 4, 8, and 16 IU PMSG were 8.8, 12.9, and 14.2, respectively. The corresponding means for numbers of implanted embryos were 9.7, 15.4, and 18.8; for numbers of corpora lutea of pregnancy (CLP), 10.8, 20.8, and 48.1; for fetal weight, 2.25, 1.65, and 1.38 g; for placental weight, 0.47, 0.38, and 0.36 g; for peripheral serum estradiol concentration, 104, 125, and 112 pg/ml; and for peripheral serum progesterone concentration, 91, 112, and 164 ng/ml. Serum estradiol levels were more correlated to numbers of live fetuses than to numbers of CLP (r = 0.32, 0.01<P<0.05; r = 0.26, 0.01<P<0.05, n = 57, respectively), whereas serum progesterone levels were more correlated to numbers of CLP than to numbers of live fetuses (r = 0.71, P<0.001; r = 0.36, 0.001<P<0.01, n = 57, respectively).

Of the pregnant rats which received 8 IU and 16 IU PMSG, 19% and 38%, respectively, had mean fetal weights of less than 1.0 g at Day 22. In most of these animals fetal weights were within the range 0.1-0.4 g, suggesting a delay of up to several days in the time of implantation. This was confirmed by the finding of substantial numbers of free blastocysts, some of which were just beginning to implant, in 12 of 36 rats whose uteri were flushed on Day 10 (i.e., 8 days after ovulation). Some of the rats given 16 IU PMSG on Day 0 were also given 50 ng estradiol at 1500 h on Day 6. Fetal weights in these animals were uniformly high at Day 22, with a mean of 1.60 g, indicating that there was insufficient nidatory estrogen in some rats treated with 16 IU PMSG alone. Implantation did not occur after mating in 20% of rats given 16 IU PMSG or in any of the rats given 40 IU PMSG, although ovulation and fertilization did occur in animals given 40 IU PMSG. The results indicate that the factors which may delay or interrupt normal gestation in superovulated rats are complex and change with increasing doses of PMSG.

Note:
ACKNOWLEDGMENTS We thank Ms. Joan Calaresu, Ms. Mira Dobias, and Mr. Gerald Barbe for their valuable technical assistance, and Dr. Thomas Kennedy for helpful discussions during the course of this study.




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Copyright © 1981 by the Society for the Study of Reproduction.