Ovarian follicular cells have innate immune capabilities that modulate their endocrine function.
Ovarian follicular cells have innate immune capabilities that modulate their endocrine function.
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DOI：
10.1530/rep-07-0229
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发表时间：
2007-11
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影响因子：
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通讯作者：
Sheldon IM
中科院分区：
文献类型：
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作者：
Herath S;Williams EJ;Lilly ST;Gilbert RO;Dobson H;Bryant CE;Sheldon IM
雌激素在卵巢卵泡的生长、发育和功能中起关键作用，在类固醇生成、卵母细胞的滋养和排卵中起重要作用。大肠杆菌等细菌感染至少部分通过干扰卵泡功能引起哺乳动物不育，其特征是抑制雌二醇的产生。在促性腺激素如FSH的调节下，卵巢卵泡颗粒细胞通过卵泡膜细胞中雄烯二酮的芳香化产生雌二醇。E.大肠杆菌通过其表面分子脂多糖（LPS）与免疫细胞上的Toll样受体-4（TLR 4）、CD 14、MD-2受体复合物结合来介导对卵巢的免疫作用，但免疫细胞不存在于卵泡内。本研究验证了颗粒细胞表达TLR 4复合物和LPS直接干扰其雌二醇分泌的假设。来自募集或优势卵泡的颗粒细胞在体内暴露于LPS，当它们在体外培养时，在没有免疫细胞污染的情况下，它们在用LPS挑战时产生较少的雌二醇，尽管卵泡膜细胞雄烯二酮的产生没有变化。LPS对雌二醇产生的抑制与颗粒细胞芳香化酶转录物的下调有关，但不影响细胞存活。此外，这些细胞表达TLR 4，CD 14和MD-2的转录在整个卵泡生长和发育的关键阶段。似乎颗粒细胞具有检测细菌感染的免疫能力，细菌感染干扰卵泡类固醇生成，这可能是细菌感染期间卵泡生长和功能受到干扰的机制。
Oestrogens are pivotal in ovarian follicular growth, development and function, with fundamental roles in steroidogenesis, nurturing the oocyte and ovulation. Infections with bacteria such as Escherichia coli cause infertility in mammals at least in part by perturbing ovarian follicle function, characterised by suppression of oestradiol production. Ovarian follicle granulosa cells produce oestradiol by aromatisation of androstenedione from the theca cells, under the regulation of gonadotrophins such as FSH. Many of the effects of E. coli are mediated by its surface molecule lipopolysaccharide (LPS) binding to the Toll-like receptor-4 (TLR4), CD14, MD-2 receptor complex on immune cells, but immune cells are not present inside ovarian follicles. The present study tested the hypothesis that granulosa cells express the TLR4 complex and LPS directly perturbs their secretion of oestradiol. Granulosa cells from recruited or dominant follicles are exposed to LPS in vivo and when they were cultured in the absence of immune cell contamination in vitro they produced less oestradiol when challenged with LPS, although theca cell androstenedione production was unchanged. The suppression of oestradiol production by LPS was associated with down-regulation of transcripts for aromatase in granulosa cells, and did not affect cell survival. Furthermore, these cells expressed TLR4, CD14 and MD-2 transcripts throughout the key stages of follicle growth and development. It appears that granulosa cells have an immune capability to detect bacterial infection, which perturbs follicle steroidogenesis, and this is a likely mechanism by which ovarian follicle growth and function is perturbed during bacterial infection.