Integrative Medicine Research Centre of Reproduction and Heredity, the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
Department of Obstetrics and Gynaecology, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Hum Reprod Update. 2019 Mar 1;25(2):224-242. doi: 10.1093/humupd/dmy047.
Neurotrophins [nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4)] and glial cell line-derived neurotrophic factor (GDNF) are soluble polypeptide growth factors that are widely recognized for their roles in promoting cell growth, survival and differentiation in several classes of neurons. Outside the nervous system, neurotrophin (NT) and GDNF signaling events have substantial roles in various non-neural tissues, including the ovary.
The molecular mechanisms that promote and regulate follicular development and oocyte maturation have been extensively investigated. However, most information has been obtained from animal models. Even though the fundamental process is highly similar across species, the paracrine regulation of ovarian function in humans remains poorly characterized. Therefore, this review aims to summarize the expression and functional roles of NTs and GDNF in human ovarian biology and disorders, and to describe and propose the development of novel strategies for diagnosing, treating and preventing related abnormalities.
Relevant literature in the English language from 1990 to 2018 describing the role of NTs and GDNF in mammalian ovarian biology and phenotypes was comprehensively selected using PubMed, MEDLINE and Google Scholar.
Studies have shown that the neurotrophins NGF, BDNF, NT-3 and NT-4 as well as GDNF and their functional receptors are expressed in the human ovary. Recently, gathered experimental data suggest putative roles for NT and GDNF signaling in the direct control of ovarian function, including follicle assembly, activation of the primordial follicles, follicular growth and development, oocyte maturation, steroidogenesis, ovulation and corpus luteum formation. Additionally, crosstalk occurs between these ovarian regulators and the endocrine signaling system. Dysregulation of the NT system may negatively affect ovarian function, leading to reproductive pathology (decreased ovarian reserve, polycystic ovary syndrome and endometriosis), female infertility and even epithelial ovarian cancers.
A comprehensive understanding of the expression, actions and underlying molecular mechanisms of the NT/GDNF system in the human ovary is essential for novel approaches to therapeutic and diagnostic interventions in ovarian diseases and to develop more safe, effective methods of inducing ovulation in ART in the treatment of female infertility.
神经生长因子（NGF）、脑源性神经营养因子（BDNF）、神经营养因子-3（NT-3）和神经营养因子-4（NT-4）以及胶质细胞源性神经营养因子（GDNF）是可溶性多肽生长因子，它们在促进多种神经元的细胞生长、存活和分化方面的作用得到了广泛认可。在神经系统之外，神经营养素（NT）和 GDNF 信号事件在包括卵巢在内的各种非神经组织中发挥着重要作用。
促进和调节卵泡发育和卵母细胞成熟的分子机制已经得到了广泛的研究。然而，大多数信息都是从动物模型中获得的。尽管基本过程在物种间高度相似，但人类卵巢功能的旁分泌调节仍知之甚少。因此，本综述旨在总结 NT 和 GDNF 在人卵巢生物学和疾病中的表达和功能作用，并描述和提出用于诊断、治疗和预防相关异常的新策略。
使用 PubMed、MEDLINE 和 Google Scholar 全面检索了 1990 年至 2018 年描述 NT 和 GDNF 在哺乳动物卵巢生物学和表型中的作用的英文相关文献。
研究表明，神经生长因子 NGF、BDNF、NT-3 和 NT-4 以及 GDNF 及其功能受体在人卵巢中表达。最近，收集到的实验数据表明，NT 和 GDNF 信号在直接控制卵巢功能方面具有潜在作用，包括卵泡组装、原始卵泡激活、卵泡生长和发育、卵母细胞成熟、类固醇生成、排卵和黄体形成。此外，这些卵巢调节剂与内分泌信号系统之间存在串扰。NT 系统的失调可能会对卵巢功能产生负面影响，导致生殖病理（卵巢储备减少、多囊卵巢综合征和子宫内膜异位症）、女性不孕，甚至上皮性卵巢癌。
全面了解 NT/GDNF 系统在人卵巢中的表达、作用和潜在分子机制，对于在卵巢疾病中进行治疗和诊断干预的新方法以及开发更安全、有效的方法来诱导女性不孕的 ART 中的排卵至关重要。
