Excessive nerve growth factor impairs bidirectional communication between the oocyte and cumulus cells resulting in reduced oocyte competence

Yiwen Zhai,Xiaoyuan Song,Guidong Yao,Fei Sun,Yong Wang,Faiza Rao

doi:10.1186/s12958-018-0349-7

Abstract

BackgroundExcessive nerve growth factor (NGF) is commonly found in the follicular fluid of patients with polycystic ovary syndrome (PCOS). Furthermore, oocytes from PCOS patients exhibit lower developmental competence. The purpose of this study was to explore the association between excessive NGF and low oocyte competence in vitro.MethodsExcessive NGF was added to mouse cumulus oocyte complexes (COCs) cultured in vitro to investigate meiotic maturation of the oocyte. After culture, mRNA expression levels of Pfkp and Ldha genes in cumulus cells (CCs) and Gdf9, Bmp15 and Fgf8 genes in oocytes, were determined by real-time quantitative polymerase chain reaction (qPCR). We also investigated the mRNA content of Pfkp and Ldha in CCs from PCOS and non-PCOS patients.ResultsExcessive NGF significantly inhibited oocyte meiotic maturation. The inhibitory effect was mediated by the NGF high-affinity receptor, NTRK1. mRNA content of Pfkp and Ldha genes in CCs was significantly reduced by excessive NGF stimulation. Moreover, the expression levels of Gdf9, Bmp15 and Fgf8 were also decreased in oocytes, and was induced by excessive NGF-stimulated CCs. In addition, lower expression levels of Pfkp and Ldha in CCs were identified in Chinese PCOS patients with excessive NGF (PCOS, 22 ± 2.63 ng/ml, n = 13; non-PCOS, 7.18 ± 2.42 ng/ml, n = 9; p < 0.01) in the follicular fluid, suggesting a potential association between excessive NGF and decreased glycolysis in the CCs of women with PCOS.ConclusionsExcessive NGF impairs bidirectional communication between oocyte and cumulus cells, which might be related to low oocyte competence.

Highlights

Excessive nerve growth factor (NGF) is commonly found in the follicular fluid of patients with polycystic ovary syndrome (PCOS)
We found that excessive NGF inhibited oocyte maturation in mouse Cumulus-oocyte complex (COC), and that the inhibitory effect was mediated by the bidirectional communication between oocyte and cumulus cells (CCs)
Excessive NGF is present in the follicular fluid of PCOS patients and inhibits oocyte maturation in vitro We firstly detected NGF content in follicular fluid of Chinese PCOS patients

Summary

Introduction

Excessive nerve growth factor (NGF) is commonly found in the follicular fluid of patients with polycystic ovary syndrome (PCOS). Nerve growth factor (NGF) is a member of the neurotrophin family [1]. While originally reported to exert functionality in the nervous system, NGF has been found to play important roles in the reproductive system [1, 2]. Various types of cells in the mammalian ovary, including theca cells, granulosa cells and cumulus cells (CCs) have been reported to produce NGF [1, 3]. NGF failed to enhance oocyte maturation and developmental competence in pigs and cows [9, 12]. The function of NGF in the process of oocyte maturation remains rather controversial and is in need of further elucidation

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