Androgens as double-edged swords: Induction and suppression of follicular development

Abstract

Androgens, which are mediated via the androgen receptor (AR), play important roles in normal follicular development and female fertility. However, just like a double-edged sword, besides the positive effects of androgen on follicular development, abnormal androgen levels, especially as in hyperandrogenism, seriously suppress normal follicular development. A crucial balance exists between the importance of androgens in follicular development and their negative effects when in excess. As the first meiotic division and epigenetic reprogramming are two critical events in oogenesis, abnormal androgen levels or deficiency in androgen/AR signaling in the ovary may affect these vital events. Oocytes have a tendency to develop genomic instability, thus resulting in an increasing incidence of unpredictable adult diseases. Although many studies have explored the effects of androgens and AR on follicular development, the conclusions are controversial and there has been no thorough review of this topic. This review focuses on the roles of androgens in the physiological process of follicular development, summarizes new insights into the roles of androgens in the arrested development of follicles, and discusses the potential risk of adult diseases originating from abnormal follicular androgen levels or androgen receptor signals, which may determine areas for future studies.

Prenatal androgen induced lean PCOS impairs mitochondria and mRNA profiles in oocytes

“…Finally, as these changes in the oocyte mitochondria are transferred to the offspring, this may explain the inheritance pattern seen in the offspring of PCOS patients (53). PCOS is well known to be hereditary, though numerous studies investigating the genetic contributions to the disease have been unable to identify strong gene candidates to explain this pattern (54,55,56).…”

Ovulation induction in polycystic ovary syndrome

“…LH stimulates androgen synthesis by theca cells, while FSH stimulates aromatization of androgens to estrogen by granulosa cells, and follicle maturation. Intraovarian androgens stimulate the growth of preantral and early antral follicle stages, thereby promoting initial follicle recruitment, while elevated androgen levels induce atresia in later antral stages . This pro‐atretic effect of androgens commences when folliculogenesis switches from the gonadotropin‐independent, initial phase to the FSH‐dependent cyclic recruitment phase at a follicular diameter of approximately 2‐5 mm .…”

Aberrant expression and DNA methylation of lipid metabolism genes in PCOS: a new insight into its pathogenesis

“…Ovarian androgen excess is the most typical pathological manifestation of PCOS [ 1 , 15 ]. The mechanisms underlying androgen excess and abnormal follicular development in PCOS remain to be elucidated.…”