The Time of Prenatal Androgen Exposure Affects Development of Polycystic Ovary Syndrome-Like Phenotype in Adulthood in Female Rats

BACKGROUND Polycystic ovary syndrome (PCOS) is one of the most common reproductive disorders in women. Previous studies have shown that prenatal exposure of female fetuses to androgen can be considered an important factor in the development of PCOS. OBJECTIVES In the present study we aimed to examine the effects of prenatal exposure of female rat fetuses to previously documented doses of testosterone on different embryonic days on the development of PCOS phenotype in adulthood. MATERIALS AND METHODS Pregnant rats were divided into four groups, experimental and control groups. Three mg of free testosterone was administered subcutaneously to experimental group 1 on gestational days 16-19, daily and 20 mg on day 20, to experimental group 2, and the controls received solvent at the same times. Female offspring of these mothers aged between 90-100 days were examined for development and function of the reproductive system. Independent-sample student t test was used to compare the results between the experimental groups and controls. RESULTS Anogenital distance (P < 0.001) and clitoris length were significantly increased in the offspring of both experimental groups (P < 0.001 and P < 0.05 respectively). Nipples were not formed in the offspring of experimental group 1, whereas in experimental group 2 the number of nipples was unchanged. Vaginal length was significantly decreased in the offspring of experimental group 1 (P < 0.001), whereas in experimental group 2, no significant difference was observed. In the offspring of experimental group 1, hormonal profiles did not differ, but in experimental group 2, levels of testosterone (P < 0.05) and LH (P < 0.01) were significantly increased, but estrogen (P < 0.05) and anti-Mullerian hormone levels (P < 0.001) were significantly decreased. A significant increase in the number of preantral and antral follicles was observed in the ovaries of offspring of experimental group 1 (P < 0.05); whereas there was no such a difference in experimental group 2. CONCLUSIONS The time of prenatal exposure to androgens may have a significant role in the development of PCOS. Increased prenatal androgen levels are associated with hormonal changes and morphological disorders of the reproductive system. Therefore, avoiding exposure to androgen excess during critical periods of fetal development may prevent or reduce adulthood PCOS manifestations caused by prenatal excess androgen.