Hum. Reprod. Advance Access published online on September 9, 2009
Human Reproduction, doi:10.1093/humrep/dep324
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early prenatal androgenization results in diminished ovarian reserve in adult female rhesus monkeys
1 National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA 2 Department of Obstetrics and Gynecology, University of Wisconsin, Madison, WI 53792, USA 3 Endocrinology-Reproductive Physiology Training Program, University of Wisconsin, Madison, WI 53706, USA 4 Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA
5 Correspondence address. 1 South Park St, Suite 555, Madison, WI, USA. E-mail: danieldumesic{at}aol.com
BACKGROUND: Early prenatal androgenization (PA) accelerates follicle differentiation and impairs embryogenesis in adult female rhesus monkeys (Macaca mulatta) undergoing FSH therapy for IVF. To determine whether androgen excess in utero affects follicle development over time, this study examines whether PA exposure, beginning at gestational days 40–44 (early treated) or 100–115 (late treated), alters the decline in serum anti-Mullerian hormone (AMH) levels with age in adult female rhesus monkeys and perturbs their ovarian response to recombinant human FSH (rhFSH) therapy for IVF.
METHODS: Thirteen normal (control), 11 early-treated and 6 late-treated PA adult female monkeys had serum AMH levels measured at random times of the menstrual cycle or anovulatory period. Using some of the same animals, basal serum AMH, gonadotrophins and steroids were also measured in six normal, five early-treated and three late-treated PA female monkeys undergoing FSH therapy for IVF during late-reproductive life (>17 years); serum AMH also was measured on day of HCG administration and at oocyte retrieval.
RESULTS: Serum AMH levels in early-treated PA females declined with age to levels that were significantly lower than those of normal (P 
0.05) and late-treated PA females (P 0.025) by late-reproductive life. Serum AMH levels positively predicted numbers of total/mature oocytes retrieved, with early-treated PA females having the lowest serum AMH levels, fewest oocytes retrieved and lowest percentage of females with fertilized oocytes that cleaved.
CONCLUSIONS: Based on these animals, early PA appears to program an exaggerated decline in ovarian reserve with age, suggesting that epigenetically induced hormonal factors during fetal development may influence the cohort size of ovarian follicles after birth.
Key words: prenatal androgens/anti-Mullerian hormone/aging/ovarian reserve/IVF
Submitted on March 31, 2009; resubmitted on August 3, 2009; accepted on August 17, 2009.