关键词: Gut microbiota Mouse Niacinamide metabolism Premature ovarian insufficiency Sleep deprivation

Mesh : Animals Female Primary Ovarian Insufficiency / metabolism Gastrointestinal Microbiome Mice Dysbiosis / microbiology metabolism Metabolomics / methods Sleep Deprivation / complications metabolism Ovarian Follicle / metabolism Oocytes / metabolism Fecal Microbiota Transplantation Disease Models, Animal Apoptosis

来  源:   DOI:10.7150/thno.95197   PDF(Pubmed)

Abstract:
Rationale: Currently, there are occasional reports of health problems caused by sleep deprivation (SD). However, to date, there remains a lack of in-depth research regarding the effects of SD on the growth and development of oocytes in females. The present work aimed to investigate whether SD influences ovarian folliculogenesis in adolescent female mice. Methods: Using a dedicated device, SD conditions were established in 3-week old female mice (a critical stage of follicular development) for 6 weeks and gut microbiota and systemic metabolomics were analyzed. Analyses were related to parameters of folliculogenesis and reproductive performance of SD females. Results: We found that the gut microbiota and systemic metabolomics were severely altered in SD females and that these were associated with parameters of premature ovarian insufficiency (POI). These included increased granulosa cell apoptosis, reduced numbers of primordial follicles (PmFs), correlation with decreased AMH, E2, and increased LH in blood serum, and a parallel increased number of growing follicles and changes in protein expression compatible with PmF activation. SD also reduced oocyte maturation and reproductive performance. Notably, fecal microbial transplantation from SD females into normal females induced POI parameters in the latter while niacinamide (NAM) supplementation alleviated such symptoms in SD females. Conclusion: Gut microbiota and alterations in systemic metabolomics caused by SD induced POI features in juvenile females that could be counteracted with NAM supplementation.
摘要:
理由:目前,偶尔会有睡眠剥夺(SD)引起的健康问题的报告。然而,到目前为止,关于SD对雌性卵母细胞生长发育的影响仍缺乏深入研究。本工作旨在研究SD是否会影响青春期雌性小鼠的卵巢卵泡发育。方法:使用专用设备,在3周龄雌性小鼠(卵泡发育的关键阶段)中建立SD条件6周,并分析肠道微生物群和系统代谢组学。分析与SD雌性卵泡发育和生殖性能参数有关。结果:我们发现SD女性的肠道菌群和系统代谢组学发生了严重改变,并且这些与卵巢早衰(POI)的参数有关。这些包括增加颗粒细胞凋亡,原始卵泡(PmFs)数量减少,与AMH降低相关,血清中的E2和LH升高,与PmF激活相容的卵泡数量和蛋白质表达的变化平行增加。SD还降低了卵母细胞的成熟和繁殖性能。值得注意的是,从SD雌性到正常雌性的粪便微生物移植在后者中诱导了POI参数,而补充烟酰胺(NAM)减轻了SD雌性的此类症状。结论:SD诱导的幼年女性POI特征引起的肠道菌群和系统代谢组学变化,可以用NAM补充剂抵消。
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