产前宫内高AMH和高雄激素暴露对子代小鼠肠道菌群的影响

doi:10.12280/gjszjk.20250629

摘要/Abstract

摘要：

目的：探讨产前宫内高抗米勒管激素（anti-Müllerian hormone，AMH）和高雄激素暴露对子1代（F1）小鼠肠道菌群的影响。方法：将F0孕鼠随机分为3组，在孕16.5 d至孕18.5 d分别给予苯甲酸苄酯+芝麻油、苯甲酸苄酯+芝麻油+AMH、苯甲酸苄酯+芝麻油+双氢睾酮皮下注射，模拟F0激素环境改变的状态。待F1子代出生后分别设为对照组（Con组）、产前高AMH组（PAMH组）和产前高雄激素组（PNA组），F1成年时评估其动情周期并收集卵巢组织和盲肠内容物分别做组织形态学观察及16S扩增子测序分析小鼠肠道菌群。结果：与Con组比较，PAMH组和PNA组F1小鼠动情周期紊乱且出现卵巢组织PCOS样的改变，且肠道菌群结构发生了改变。结合功能分析可知PAMH组和PNA组小鼠肠道菌群改变主要富集于免疫系统及代谢信号通路。结论：产前宫内高AMH和高雄激素暴露改变了F1小鼠肠道菌群结构，这可能与免疫系统及代谢通路有关。

关键词: 多囊卵巢综合征, 胃肠道微生物组, 雄激素类, 抗米勒管激素, 动物实验

Abstract:

Objective: To examine the impact of prenatal intrauterine exposure to high anti-Müllerian hormone (AMH) and androgen on the gut microbiota in F1 offspring mice. Methods: Pregnant F0 dams were randomly allocated into three groups. To simulate altered prenatal hormonal environments, F0 dams received daily subcutaneous injections from embryonic day 16.5 to embryonic day 18.5 as follows: benzyl benzoate with sesame oil, benzyl benzoate with sesame oil and anti-Müllerian hormone (AMH), or benzyl benzoate with sesame oil and dihydrotestosterone. Their female F1 offspring were correspondingly designated as the control group (Con group), prenatal AMH group (PAMH group), and prenatal androgenized group (PNA group). Upon reaching adulthood, the estrous cycle of F1 female offsprings were monitored and assessed for regularity. Ovarian tissue and cecal contents were collected for histological evaluation and gut microbiota profiling via 16S amplicon sequencing. Results: Compared to the Con group, the PNA and PAMH groups exhibited disrupted estrous cyclicity and notable histological abnormalities in ovarian morphology, while F1 offspring mice showed significant alterations in gut microbial composition. Functional predictive analysis indicated that the differentially enriched microbial taxa were predominantly involved in immune regulation and metabolic pathways. Conclusions: Prenatal intrauterine exposure to high AMH and androgen reshaped the gut microbiota structure of F1 offspring mice, which may be associated with the immune system and metabolic pathways.

Key words: Polycystic ovary syndrome, Gastrointestinal microbiome, Androgens, Anti-müllerian hormone, Animal experimentation

刘英, 宁舒婷, 张春仁, 戴芳, 莫慧滢, 马红霞. 产前宫内高AMH和高雄激素暴露对子代小鼠肠道菌群的影响[J]. 国际生殖健康/计划生育杂志, 2026, 45(2): 97-103.

LIU Ying, NING Shu-ting, ZHANG Chun-ren, DAI Fang, MO Hui-ying, MA Hong-xia. Effect of Prenatal Intrauterine Exposure to High Anti-Müllerian Hormone and Androgen on the Gut Microbiota of Offspring Mice[J]. Journal of International Reproductive Health/Family Planning, 2026, 45(2): 97-103.

图/表 4

图1 小鼠动情周期变化曲线与卵巢组织形态学表现注：A 小鼠动情周期折线图；B 小鼠卵巢组织病理图，HE×6.3，标尺=500 μm。* 黄体；▲ 囊状卵泡。

图2 小鼠肠道菌群多样性分析注：A 小鼠肠道菌群OTU个数韦恩图；B 小鼠肠道菌群β多样性分析图；C 小鼠肠道菌群α多样性指数分析图。PC1 第一主成分；PC2 第二主成分；NMDS1 非度量多维尺度分析第一轴；NMDS2 非度量多维尺度分析第二轴。* Con vs. PAMH，P<0.05；# Con vs. PNA，P<0.05。

图3 肠道微生物组成差异分析注：A 小鼠肠道菌群种、属、门水平物种组成柱形图；B 小鼠肠道菌群种、属、门水平关键物种差异比较图；C 小鼠肠道菌群LEfSe聚类图和LEfSe LDA图。

图4 肠道微生物功能差异分析注：A 差异表达COG功能分析图（Con vs. PAMH）；B 差异表达KEGG富集分析图（Con vs. PAMH）；C 差异表达COG功能分析图（Con vs. PNA）；D 差异表达功能差异分析KEGG富集分析图（Con vs. PNA）。

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