Rno-miR-128-3p promotes apoptosis in rat granulosa cells (GCs) induced by norepinephrine through Wilms tumor 1 (WT1)

Ming Li,Ling Xue,Feng Li,Weibin Xu,Pingping Liu

doi:10.1007/s11626-021-00609-y

Abstract

The mechanism related to ovarian follicular is complex, which has not been fully elucidated. Abundant reports have confirmed that the ovarian function development is closely related to sympathetic innervation. As one of the major neurotransmitters, norepinephrine (NE) is considered an effective regulator of ovarian functions like granulosa cell (GC) apoptosis. However, the mechanism between NE and GC apoptosis in rat is still unclear. In our study, GCs were isolated and cultured in vitro with NE treatment. The apoptosis of GCs was facilitated by NE. Wilms tumor 1 (WT1) was found to be significantly downregulated in GCs after NE treatment, and overexpression of WT1 repressed apoptosis in rat GCs induced by NE. rno-miR-128-3p was found to be significantly enhanced by NE in GCs, and inhibition of rno-miR-128-3p repressed apoptosis in rat GCs induced by NE. Mechanistically, rno-miR-128-3p interacted with WT1 and repressed its expression. In summary, inhibition of rno-miR-128-3p may enhance WT1 expression, and then repress NE-induced apoptosis in rat GCs. Our research may provide a new insight for the improvement of ovarian follicular development.

Highlights

Follicle development is a complex physiological process that is crucial to ovarian function and fertility (Fortune 1994)
NE induces apoptosis in rat granulosa cell (GC) and represses the expression levels of Wilms tumor 1 (WT1) After treating with different concentrations of NE, the apoptosis of GCs was assessed by the TUNEL assay and flow cytometry assay
Our data exhibited that both mRNA and protein of WT1 were decreased by NE treatment and showed NE concentration dependence (Fig. 1E); 10 μmol/L NE was selected for subsequent experiments

Summary

Introduction

Follicle development is a complex physiological process that is crucial to ovarian function and fertility (Fortune 1994). As one of the major neurotransmitters, norepinephrine (NE) is considered an effective regulator of ovarian functions like granulosa cell (GC) apoptosis (Zhang et al 2017a). A study conducted by Patel et al (2015) found that NE decreases ROS and DNA injury in ovarian surface epithelial cells. NE is reported to be related with the ROS production in GCs, which acts as important factors in ovarian physiology, like ovulation (Saller 2012). It is not clear whether and how NE affects the GC apoptosis in rat

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