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Biology of Reproduction, Vol 24, 913-921, Copyright © 1981 by Society for the Study of Reproduction

Acute Gonadotropin Deprivation. I. A Model for the Study of Follicular Atresia

CHARLES H. BILL II 1, and GILBERT S. GREENWALD 1

1 Department of Anatomy and Department of Physiology, University of Kansas Medical Center, Kansas City, Kansas 66103


A model for the study of atresia in antral follicles is described. Follicular development and atresia was induced in hypophysectomized hamsters using pregnant mares serum (PMS) followed by rabbit-anti-PMS (PMS-As). Adult hamsters were hypophysectomized on Day 1 (metestrus); following surgery each animal received 30 IU of PMS (s.c.). PMS-As (100 µl, undiluted) was administered i.p. on Day 4.

Serum E2 underwent the greatest increase between Days 2 and 3, reaching a maximal concentration of 1030 ± 164 (mean ± SEM) pg/ml at 0900 h on Day 4. There was no change in E2 concentration (in the absence of PMS-As) on Day 5. Serum P concentration fell from 6.1 ± 1.5 ng/ml on Day 3 to 1.7 ± 0.3 ng/ml on Day 4, indicating luteal regression. Gonadotropin support of follicles was maximal through Day 4, as determined by radioimmunoassay of serum PMS. Between Days 4 and 5 the serum concentration of PMS dropped by 50%. One hour following treatment with PMS-As, serum estradiol fell to 461 ± 80 pg/ml. By 2 h the concentration was 150 ± 6 pg/ml; by 8 h, 45 ± 2 pg/ml; and by 24 h the hormone was undetectable. Serum progesterone had dropped by Day 4 and did not change significantly over the 24 h interval following PMS-As. Pyknosis of granulosa cell nuclei was first observed 4 h following PMS-As treatment. Granulosa cell degeneration began in the cumulus oophorus and then spread to the peripheral cells. By 24 h the nuclear envelope of the oocyte disappeared and the chromatin was seen in various stages of meiotic division; however, no polar bodies were observed.

Administration of various amounts of PMS-As (0.1-100 µl) at 0900 h of Day 4, revealed that within the dose range of 3.0-100 µl, the antiserum maximally reduced serum E2 by 1700 h. Graded effects were observed when doses of 0.1-1.0 µl were administered. An antiserum to ovine LH was equally effective as PMS-As (at a dose of 100 µl) in drastically reducing serum levels of E2 by 1700 h.

This animal model offers a new approach to the study of follicular atresia by providing a large population of antral follicles in which the precise time of onset of atresia is known. Furthermore, these results provide indirect evidence that significant changes in follicular steroidogenesis precede structural alterations.

Note:
ACKNOWLEDGMENTS The authors wish to thank Darlene Limback for her excellent technical assistance. The research was sponsored by grants from NIH (HD00596) and the Ford Foundation. We thank NIAMDD for furnishing the PMS, Dr. D. C. Johnson for supplying the PMS-antiserum, and Dr. William Hansel for supplying the LH-antiserum.

Submitted on September 19, 1980
Accepted on January 12, 1981




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