Vaginal extracellular vesicles impair fertility in endometriosis by favoring Th17/Treg imbalance and inhibiting sperm activity

Zuo Zhang, Zhang Zuo, Zhang Z, Yangbai Xiong, Xiong Y, Huifu Jiang, Jiang H, Hui Jiang, Wang Q, Qian Wang, Hu X, Xinyue Hu, Wei X, Xin Wei, Chen Q, Qi Chen, Tingtao Chen
Journal of cellular physiology · 2024 · vol. 239(4) , pp. e31188 · doi:10.1002/jcp.31188 · PMID:38192157 · W4390769320
article OA: closed CC0 ⤵ 4 in-corpus citations
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Vaginal extracellular vesicles from women with endometriosis impair sperm motility, acrosome reaction, and intracellular calcium levels, while promoting Th17/Treg imbalance and reducing fertility in mice.

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Abstract

Extracellular vesicles (EVs) play a key role in various diseases. However, their effect on endometriosis (EMs)-associated infertility is poorly understood. We co-cultured EVs from the female vaginal secretions with human sperm and also generated a mouse model of EMs by allogenic transplant to explore the effect of EVs on fertility. EVs from individuals with EMs-associated infertility (E-EVs) significantly inhibited the total motility (26.46% vs. 47.1%), progressive motility (18.78% vs. 41.06%), linear velocity (21.98 vs. 41.91 µm/s) and the acrosome reaction (AR) rate (5% vs. 22.3%) of human sperm in contrast to the control group (PBS). Furthermore, E-EVs dose-dependently decreased the intracellular Ca2+ ([Ca2+]i), a pivotal regulator of sperm function. Conversely, healthy women (H-EVs) increased human sperm motion parameters, the AR rate, and sperm [Ca2+]i. Importantly, the mouse model of EMs confirmed that E-EVs further decreased the conception rate and the mean number of embryo implantations (7.6 ± 3.06 vs. 4.5 ± 3.21) compared with the control mice by inducing the production of inflammatory cytokines leading to a Th17/Treg imbalance. H-EVs could restore impaired fertility by restoring the Th17/Treg balance. We determined the impact of EVs derived from the female genital tract on human sperm function and studied the possible mechanisms by which it affects fertility. Our findings provide a novel rationale to ameliorate EMs-associated infertility.

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Condition tags

endometriosisinfertility

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

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