Hormonal regulation of microRNA expression in the ovary

Abstract

The ovary is a dynamic organ that is charged with the responsibility of producing a viable gamete so that the circle of life can be reproduced for future generations. The ovary is also responsible for producing, secreting, and maintaining the proper hormone milieu of estrogens and progesterone for maintenance of pregnancy and the overall fitness of a woman's health. Understanding the mechanisms that regulate the interplay between hormone action and biological function is critical for furthering our knowledge of fertility and reproductive health. For decades, research has been conducted on understanding the transcriptional regulation of ovarian gene expression and how this relates to reproductive function. Recently, attention has turned to alternative forms of gene regulation, including post-transcriptional gene regulation. One mechanism of post-transcriptional gene regulation is the expression and function of microRNA (miRNA). These highly conserved, short, non-coding RNA molecules primarily silence gene expression by directly interfering with protein translation or causing the degradation of messenger RNA. The focus of these studies was to first determine if miRNA are necessary for female fertility. Conditional deletion of Dicer, a key processing enzyme in miRNA biogenesis, in ovarian granulosa cells, the oviduct, and uterus, led to a drastic decrease in ovulation rate and complete infertility in female mice. To further investigate the role of miRNA in ovulation, we next investigated miRNA-212 and -132. While these two co-transcribed miRNA were highly induced by the luteinizing hormone surge immediately prior to ovulation, they did not appear to have an effect on female fertility in the mouse. In a second series of studies, we analyzed the regulation of miRNA by hormones in two in vivo models. We found that miRNA expression was altered in theca cells from women suffering from polycystic ovarian syndrome (PCOS) and that expression of miRNA was altered in the fetal ovaries of sheep exposed to an excess of prenatal androgens. Taken together, these studies provide evidence that miRNA are crucial for female fertility and ovarian function and that hormones influence the expression of ovarian miRNA in diseased states. These studies support the need for further study to understand the mechanisms through which these post-transcriptional regulators affect ovarian function, so that we can potentially use them as a therapeutic target to help overcome infertility and/or disease.