Androgen Receptor Alternative Splicing and Human Infertility

Abstract

About 95% of multi-exonic genes express more than one mRNA and downstream proteins by alternative splicing (AS) through the inclusion or exclusion of specific exons. Although AS provides a significant advantage in human evolution by increasing proteomic diversity, deregulation of AS can result in various pathologic conditions. The androgen receptor (AR), encoded by AR gene, is a steroid receptor transcription factor which mediates the cellular functions of androgen. The AR-mediated androgen actions play important and dual roles in the human reproduction development and function. Dysregulation of AR will result in human infertility. Multiple AR alternative splicing variants have been identified in different pathologies conditions, including androgen insensitivity syndrome, which will cause male infertility. More recently, our group has identified two AR splice variants expressed in granulosa cells from patients with polycystic ovary syndrome, which is one of the most common causes of female infertility. All of the aforementioned indicate that androgen receptor alternative splicing may be an important pathogenic mechanism in human infertility. The purpose of this review is to summarize the various alternatively spliced AR variants that have been discovered, with a focus on their role and origin in the pathologies of the human infertility diseases, including polycystic ovary syndrome and androgen insensitivity syndrome.