Wang Zhibo, Zheng Jian, Yang Hua, Feng Xu, Li Fengzhe, Pang Jing, Yao Xiaolei, Wang Feng, Zhang Yanli
Jiangsu Livestock Embryo Engineering Laboratory, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
Shanghai Animal Disease Prevention and Control Center, Shanghai 201103, China.
Animals (Basel). 2025 Jun 9;15(12):1704. doi: 10.3390/ani15121704.
Toll-like receptors (TLRs) play crucial roles in innate immunity, but their function in reproduction remains poorly understood. This study investigated the expression patterns and localization of TLR1-9 in the reproductive system of Hu sheep and their potential association with prolificacy. All TLRs were expressed in the oviduct, uterus, and ovary, with TLR6 showing significantly higher expression in the oviduct, while TLR3, TLR6, and TLR7 were predominantly expressed in the ovary. Following this initial screening, we focused on TLR2, TLR6, and TLR7 for detailed analysis. Immunohistochemical analysis revealed that TLR2, TLR6, and TLR7 were localized in the luminal epithelium and circular muscle of the oviduct, the luminal and superficial glandular epithelium of the uterus, and in ovarian follicles at all developmental stages. A comparative analysis between high-prolificacy (HP) and low-prolificacy (LP) Hu sheep demonstrated significantly lower TLR2 expression in the reproductive organs of HP sheep, while TLR6 expression was higher and TLR7 expression was lower in HP ovaries compared to LP ovaries. Notably, TLR7 was observed around apoptotic bodies of granulosa cells, suggesting a potential role in follicular development through the regulation of granulosa cell apoptosis. These findings establish a novel link between innate immunity and reproductive function in sheep, suggesting that TLRs, particularly TLR2, TLR6, and TLR7, may serve dual roles as immune sentinels and reproductive regulators influencing ovine fertility.
Toll样受体（TLRs）在先天免疫中发挥着关键作用，但其在生殖中的功能仍知之甚少。本研究调查了TLR1 - 9在湖羊生殖系统中的表达模式、定位及其与繁殖力的潜在关联。所有TLR均在输卵管、子宫和卵巢中表达，其中TLR6在输卵管中的表达显著更高，而TLR3、TLR6和TLR7主要在卵巢中表达。在初步筛选之后，我们聚焦于TLR2、TLR6和TLR7进行详细分析。免疫组织化学分析显示，TLR2、TLR6和TLR7定位于输卵管的腔上皮和环行肌、子宫的腔上皮和浅表腺上皮以及所有发育阶段的卵巢卵泡中。高繁殖力（HP）湖羊和低繁殖力（LP）湖羊的比较分析表明，HP羊生殖器官中TLR2的表达显著较低，而与LP卵巢相比，HP卵巢中TLR6的表达较高，TLR7的表达较低。值得注意的是，在颗粒细胞的凋亡小体周围观察到了TLR7，提示其可能通过调节颗粒细胞凋亡在卵泡发育中发挥作用。这些发现建立了绵羊先天免疫与生殖功能之间的新联系，表明TLRs，特别是TLR2、TLR6和TLR7，可能作为影响绵羊繁殖力的免疫哨兵和生殖调节因子发挥双重作用。
