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Impaired Developmental Competence of Oocytes in Adult Prenatally Androgenized Female Rhesus Monkeys Undergoing Gonadotropin Stimulation for in Vitro Fertilization

Wisconsin Regional Primate Research Center, Department of Obstetrics and Gynecology, University of Wisconsin, Madison, Wisconsin 53715-1299; and the Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota 55905

Address all correspondence and requests for reprints to: Daniel A. Dumesic, M.D., Division of Reproductive Endocrinology, Department of OB/GYN, Mayo Clinic, Rochester, Minnesota 55905. E-mail: . ddumesic{at}mayo.edu

Abstract

To determine whether prenatal T propionate exposure beginning gestational d 40–44 (early-treated) or 100–115 (late-treated) affects oocyte competence, five early-treated and five late-treated prenatally androgenized and five normal monkeys underwent recombinant human FSH injections with oocyte-retrieval after hCG administration. Serum FSH, LH, estradiol (E₂), progesterone (P₄), androstenedione (A₄), T, and dihydrotestosterone were measured basally, during gonadotropin stimulation and at oocyte-retrieval; fasting serum glucose and insulin also were determined basally and at oocyte-retrieval. Follicle fluid sex steroids were analyzed. Oocyte number, nuclear maturity, and fertilization were comparable among female groups, but the percentage of zygotes developing into blastocysts was reduced in early-treated prenatally androgenized females. The intrafollicular P₄/E₂ ratio was significantly elevated in early-treated prenatally androgenized females, whereas intrafollicular P₄/A₄ and T/A₄ ratios were significantly increased in all prenatally androgenized females. Early-treated prenatally androgenized females demonstrated persistent LH hypersecretion. They also were unable to suppress circulating insulin levels during gonadotropin stimulation. Circulating sex steroid levels and serum P₄/E₂, P₄/A₄, and E₂/androgen ratios were similar in all females. Early prenatal androgenization in monkeys receiving gonadotropins impairs oocyte developmental competence and seems to induce premature follicle differentiation in the presence of LH hypersecretion and relative insulin excess.

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