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

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.

Combined use of Diane-35 and metformin improves the ovulation in the PCOS rat model possibly via regulating glycolysis pathway

“…Androgen could inhibit LDH-A expression to reduce lactic acid production, which has been suggested to be associated with PCOS follicular developmental disorders [35]. More importantly, excessive nerve growth factor in follicular fluid of PCOS patients can significantly reduce the expression of LDH-A, impair communication between granulosa cells and oocytes, and reduce oocyte developmental capacity [36]. Metformin treatment could increase the LDH-A expression in the endometrial tissues from PCOS patients with hyperplasia [32].…”

PCOS and Role of Cumulus Gene Expression in Assessing Oocytes Quality

“…A study on mice with type 1 diabetes (hyperglycaemic state) showed that the oocytes have poor developmental competence due to poor folliculogenesis (80), defect oogenesis, and impaired oocyte maturation (81). In women with PCOS, it was demonstrated that PFKP and Ldha genes was significantly reduced due to excessive nerve growth factor (NGF) stimulation, hence resulting in decreased glycolysis and worsening the hyperglycemic state in PCOS women (41). NGF is a member of the neutrophin family and has been found to play important role in the reproductive system in addition to its' normal function in the nervous system.…”

“…NGF is a member of the neutrophin family and has been found to play important role in the reproductive system in addition to its' normal function in the nervous system. Excessive NGF in PCOS women significantly inhibit oocyte meiotic maturation contributing to poor quality oocyte (41). There is also an alteration in follicular fluid composition in PCOS, especially with regards to the level of insulin, glucose, and lactate.…”

Shuttle Transfer of mRNA Transcripts via Extracellular Vesicles From Male Reproductive Tract Cells to the Cumulus–Oocyte Complex in Rabbits (Oryctolagus cuniculus)

“…It is also involved in ovulation inductions in cats, rabbits, and camels ( 4 , 5 , 71 ). Even though moderate levels of NGF improved oocyte maturation ( 47 , 72 , 73 ), paradoxically, excessive NGF supplementation impaired the bidirectional communication between oocytes and cumulus cells and reduced the oocyte competence ( 74 ). Our results also showed that the increased levels of NGF hindered oocyte maturation and caused a spontaneous early parthenogenetic cleavage in the oocytes.…”