卵巢旁/自分泌及降调节对其的影响

Will ovarian paracrine/autocrine be affected by GnRH agonist/GnRH antagonist down-regulation?

卵巢内卵和颗粒细胞间的双向交流既调节卵泡生成也调控卵的发生。卵和卵泡来源因子在调控窦卵泡发育和卵活性中具有阶段特异作用。转化生长因子-β(TGF-β)超家族成员,包括抑制素、激活素、卵泡抑素、骨形态形成蛋白(BMP)、生长分化因子(GDF)、抗苗勒氏管激素(AMH)等均属生长因子,可通过卵巢旁分泌和/或自分泌起到调控卵泡发育和卵成熟的作用。其它涉及旁分泌/自分泌的因子还包括表皮生长因子(EGF)、成纤维细胞生长因子(FGFs)家族、胰岛素样生长因子(IGFs)家族、血管内皮生长因子(VEGF)家族、细胞因子(cytokin)家族、白细胞介素(interleukins)、肿瘤坏死因子-α(TNF-α)等。促性腺激素释放激素(GnRH)可以作为一种自分泌因子。GnRH受体还在一些垂体以外的组织表达,GnRH可以上调GnRH受体及其基因表达。虽不清楚GnRH受体在人卵巢中是否具有功能,但GnRH拮抗剂(GnRH-ant)可能干扰人卵巢细胞内GnRH的自分泌和旁分泌信号,改变卵泡微环境。尽管存在争议,GnRH-ant对人卵巢和生长因子(如EGF,IGF-I和IGF-II等)的影响至少部分反映在卵泡生成方面,虽然其机理尚未完全阐明。故GnRH激动剂(GnRH-a)/GnRH-ant降调可能影响卵巢旁分泌/自分泌,从而影响卵泡生成/卵质量/着床/胚胎发育。

Bi-directional communication between the oocyte and cumulus cells regulates both folliculogenesis and oogenesis on ovary. Oocyte and follicle-derived factors have stage-specific roles in regulating antral follicular development and oocyte competence. Members of the transforming growth factor-β （TGF-β） superfamily, including inhibin, activin, follistatin, TGF-β, bone morphogenic protein （BMP） ,growth differentiation factor（GDF）and anti-Mullerian hormone（AMH）, are among the growth factors which regulate follicular development and oocyte maturation via paracrine and/or autocrine mechanisms. The other factors related to paracrine/autoerine include epidermal growth factor （EGF）, fibroblast growth factors （FGFs）, insulin-like growth factors （IGFs）, vascular endothelial growth factor （ VEGF）, cytokins, interleukins, tumor necrosis factor （TNF）-α, etc. GnRH may act as an autocrine factor. Expression of GnRH receptors has been demonstrated in numerous extra-pituitary tissues. GnRH up-regulates GnRH receptor and its gene expression. Although it is not clear whether GnRH receptors in the human ovary are functional,it is possible that GnRH antagonist may disrupt autocrine and paracrine signalling of GnRH in human ovarian cells, and change the intra-follicular microenvironment. The influence of GnRH antagonist on the human ovary and growth factors （e. g. EGF,IGF-I and IGF-II,etc. ）is at least partially responsible for folliculogenesis, but it has not been clearly demonstrated. Ovarian autocrine/paracrine may be affected by down-regulation of GnRH agonist/ GnRH antagonist, which will affect follieulogenesis, oocyte quality, embryo implantation and embryo development.