The current research builds on past studies, some of which were performed in the laboratory of Chawnshang Chang, Ph.D., at the University of Rochester, which have shown that completely eliminating male hormone receptors, or androgen receptors, in female mice leads to abnormal ovarian function and reduced fertility. To help determine which reproductive tissues, including the hypothalamus, pituitary, and many cells within the ovary, regulate fertility, authors of the current study removed androgen receptors from only ovarian cells, known as granulosa cells, in female mice. Androgen receptors in all other reproductive tissues, including the hypothalamus, pituitary, and other ovarian cells were left intact.

Female mice without androgen receptors in the ovarian granulosa cells had premature ovarian failure, meaning they stopped ovulating too early, and were sub-fertile, meaning they had abnormal ovulation cycles, did not ovulate as many eggs as control mice, and had smaller litter sizes. These mice also had fewer follicles that completed development and were ready to ovulate; rather, many of their follicles did not progress beyond pre-development stages and died before ovulation could occur.

These results suggest that the presence of male hormones in ovarian granulosa cells in mice is critical for normal follicle development and fertility. When androgen receptor signaling is blocked or eliminated in ovarian granulosa cells, ovarian follicles cannot progress to later stages of development, ultimately resulting in reduced fertility.

"We found that fertility problems are most likely present because androgen signaling in the ovary is abnormal," said Aritro Sen, Ph.D., research assistant professor in the division of Endocrinology and Metabolism at the University of Rochester Medical Center and a lead author of the study. "Previously, we assumed that androgen signaling in the brain - the hypothalamus and the pituitary - was at the root of the problem, but we found that is not the case."

Source: University of Rochester Medical Center