SRSFs mediate the function of AR in the ovarian granulosa cells of patients with PCOS

Jing Luo  ¹ , Hong Ye  ² , Lijuan Hao  ² , Yixuan Sun  ¹ , Ruohan Li  ¹ , Yanxi Li  ¹ , Zhu Yang  ¹ Affiliations

• PMID: 33569518
• PMCID: PMC7859457
• DOI: 10.1016/j.gendis.2019.09.005

Free PMC article

Abstract

Ovarian hyperandrogenism is one of the characteristics of polycystic ovary syndrome (PCOS) and androgen receptor (AR) in ovarian granulosa cells (GCs) functions as an important element to the accumulation of androgens. This study verified the existence of alternative splicing variant of AR (AR-SVs) in the GCs of PCOS patients and found that the function of AR decreased significantly in the presence of AR-SVs. And compared to the normal individuals, the expression of Serine/arginine-rich splicing factor 2(SRSF2) was higher and the expression of SRSF3 was lower in the GCs of patients with AR-SVs. More importantly, we found that the expression of SRSF2 was inhibited and that the expression of AR was decreased after the successful upregulation of miRNA-183, and testostrone (T) concentrations in the culture medium were increased. The results also showed that the expression of SRSF3 decreased when miRNA-124 was successfully upregulated, while the expression of AR significantly increased; however, the function of AR was also inhibited when T concentration in the culture medium was increased. This study has proved that SRSFs are regulated by corresponding miRNAs, and the altered expression of SRSFs interferenced the alternative splicing process of AR and ultimately decreased the function of AR, leading to the accumulation of androgens in the ovary.

Keywords: Androgen receptor; Granulosa cells; Hyperandrogenism; PCOS; SRSFs; miRNAs.