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Developmental Programming: Follicular Persistence in Prenatal Testosterone-Treated Sheep Is Not Programmed by Androgenic Actions of Testosterone

Departments of Pediatrics (T.S., M.M., V.P.) and Molecular and Integrative Physiology (V.P.) and the Reproductive Sciences Program (T.S., M.M., V.P.), University of Michigan, Ann Arbor, Michigan 48109-0404; and Division of Animal and Veterinary Sciences (E.K.I.), West Virginia University, Morgantown, West Virginia 26506

Address all correspondence and requests for reprints to: Vasantha Padmanabhan, Departments of Pediatrics, Obstetrics, and Gynecology, and Molecular and Integrative Physiology and the Reproductive Sciences Program, University of Michigan, 300 North Ingalls Building, Room 1109, Ann Arbor, Michigan 48109-0404. E-mail: vasantha{at}umich.edu.

Testosterone (T) treatment during early-midgestation (30–90 d; term is 147 d) 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 whether 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 nonaromatizable androgen) in cottonseed oil from d 30 to d 90 of gestation. Prior to daily transrectal ovarian ultrasonography, estrus was synchronized with two injections of 20 mg of prostaglandin F₂ (PGF₂) given 11 d apart in two consecutive years. In yr 1 ultrasonography began 14 d after PGF₂, during the presumptive luteal phase, and continued until subsequent ovulation and corpora lutea were detected (10–13 d). In yr 2, ultrasonography began 2 d before the last PGF₂ injection and concluded 25 d after the last PGF₂ 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.

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