The Robinson Research Institute and Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia.
Commun Biol. 2021 May 14;4(1):572. doi: 10.1038/s42003-021-02038-9.
Seminal fluid factors modulate the female immune response at conception to facilitate embryo implantation and reproductive success. Whether sperm affect this response has not been clear. We evaluated global gene expression by microarray in the mouse uterus after mating with intact or vasectomized males. Intact males induced greater changes in gene transcription, prominently affecting pro-inflammatory cytokine and immune regulatory genes, with TLR4 signaling identified as a top-ranked upstream driver. Recruitment of neutrophils and expansion of peripheral regulatory T cells were elevated by seminal fluid of intact males. In vitro, epididymal sperm induced IL6, CXCL2, and CSF3 in uterine epithelial cells of wild-type, but not Tlr4 null females. Collectively these experiments show that sperm assist in promoting female immune tolerance by eliciting uterine cytokine expression through TLR4-dependent signaling. The findings indicate a biological role for sperm beyond oocyte fertilization, in modulating immune mechanisms involved in female control of reproductive investment.
精液因子在受孕时调节女性免疫反应，以促进胚胎着床和生殖成功。然而，精子是否会影响这种反应尚不清楚。我们通过微阵列分析评估了与完整或输精管结扎雄性小鼠交配后小鼠子宫的全局基因表达。完整雄性诱导了更大的基因转录变化，主要影响促炎细胞因子和免疫调节基因，其中 TLR4 信号被确定为排名最高的上游驱动因素。完整雄性的精液增加了中性粒细胞的募集和外周调节性 T 细胞的扩增。在体外，附睾精子诱导野生型雌性子宫上皮细胞中产生 IL6、CXCL2 和 CSF3，但 TLR4 缺失的雌性则没有。这些实验共同表明，精子通过 TLR4 依赖性信号转导诱导子宫细胞因子表达，从而有助于促进女性免疫耐受。这些发现表明，精子在卵子受精之外，在调节女性生殖投资中涉及的免疫机制方面具有生物学作用。
