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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Inflammation

Lyg1 deficiency aggravated LPS-induced chronic epididymal inflammation and sperm dysfunction in mouse

Provisionally accepted
XueXia  LiuXueXia Liu1Yuxiao  ZhangYuxiao Zhang2Jialu  WeiJialu Wei2Benjiao  GongBenjiao Gong1Xiaoxin  WangXiaoxin Wang1Fujun  LiuFujun Liu1*
  • 1Yantai Yuhuangding Hospital, Yantai, China
  • 2Shandong Second Medical University, Weifang, China

The final, formatted version of the article will be published soon.

Chronic epididymitis negatively impairs male fertility; however, the role of LYG1 in this condition remains poorly understood. This study revealed that Lyg1 was highly expressed in the mouse epididymis, particularly in the cauda region. Under physiological conditions, Lyg1 knockout (KO) mice exhibited normal epididymal histology, sperm parameters, and fertility. Conversely, in LPS-induced chronic epididymitis models, Lyg1 deficiency significantly exacerbated cauda epididymis damage and sperm malfunction, characterized by increased collagen deposition, epithelial disarray, and reduced expression of sperm functional proteins (TSSK2, ZPBP, HSPA4L). Transcriptomic analysis demonstrated LPS treatment up-regulated immune response and metabolic pathways in wild-type (WT) mice, whereas dysregulated extracellular matrix (ECM)-receptor interaction and cell adhesion pathways in KO mice. In vitro fertilization (IVF) experiments indicated LPS treatment decreased fertilization rates in both groups, with a more pronounced decline observed in KO sperm. These findings indicated that LYG1 regulated the balance between epididymal inflammatory response and tissue repair. Targeting LYG1-dependent pathways may provide novel therapeutic strategies to mitigate fibrosis and preserve male fertility in chronic epididymitis.

Keywords: LYG1, Choronic Epididymitis, Fibrosis, Sperm function, male fertility

Received: 05 Sep 2025; Accepted: 25 Nov 2025.

Copyright: © 2025 Liu, Zhang, Wei, Gong, Wang and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Fujun Liu

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