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This version published online on April 19, 2007
Endocrinology, doi:10.1210/en.2007-0339
A more recent version of this article appeared on July 1, 2007
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Submitted on March 12, 2007
Accepted on April 11, 2007

Developmental Programming: Follicular persistence in prenatal testosterone-treated sheep is not programmed by androgenic actions of testosterone

Teresa Steckler, Mohan Manikkam, E. Keith Inskeep, and Vasantha Padmanabhan*

Departments of Pediatrics, Molecular and Integrative Physiology, and the Reproductive Sciences Program, University of Michigan, Ann Arbor, MI, Division of Animal and Veterinary Sciences, West Virginia University, Morgantown, West Virginia

* To whom correspondence should be addressed. E-mail: vasantha{at}umich.edu.

Testosterone (T) treatment during early-mid gestation (30-90 days; term is 147 days) leads to reproductive cycle defects. Daily ultrasonography in prenatal T-treated female sheep during the first two breeding seasons revealed an increase in the number of large follicles and follicular persistence. The objective of this study was to determine if follicular persistence in prenatal T-treated females was programmed by the androgenic actions of T. Pregnant Suffolk ewes were injected with 100 mg (im; twice weekly) of T propionate or dihydrotestosterone (DHT, a non-aromatizable androgen) in cottonseed oil from days 30-90 of gestation. Prior to daily transrectal ovarian ultrasonography, estrous was synchronized with two injections of 20 mg of prostaglandin F2{alpha}(PGF2{alpha})given 11 days apart in two consecutive years. In Year 1 ultrasonography began 14 days after PGF2{alpha}, during the presumptive luteal phase, and continued until subsequent ovulation and corpora lutea (CL) were detected (10-13 days). In Year 2, ultrasonography began two days before the last PGF2{alpha} injection and concluded 25 days after the last PGF2{alpha} injection. Daily changes in appearance and disappearance of ovarian follicles and follicular sizes were assessed. Prenatal DHT, but not prenatal T, treatment increased the total number of follicles by increasing the number of small follicles. Prenatal T, but not DHT, treatment increased (P < 0.05) the number of large follicles with the majority of prenatal T-treated females manifesting follicular persistence. The data indicate that occurrence of large sized follicles and follicular persistence in prenatal T-treated females are not programmed by androgenic actions, but likely are programmed by estrogenic actions stemming from aromatization of T to estradiol.


Key words: infertility • PCOS • ovary • folliculogenesis • ovulation




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