Umehara Takashi, Yamanaka Takahiro, Shimada Masayuki
Graduate School of Integrated Sciences for Life Hiroshima University Higashi-Hiroshima Japan.
Reprod Med Biol. 2025 Apr 15;24(1):e12651. doi: 10.1002/rmb2.12651. eCollection 2025 Jan-Dec.
Toll-like receptors (TLRs) are critical components of the innate immune system and are expressed in various cells, including the reproductive system. Although their roles in female reproductive tissues such as the ovaries and uterus, including their involvement in fertilization and implantation, have been extensively reviewed, their expression and function in male germ cells, particularly in sperm, remain underexplored.
This review provides a comprehensive summary of research on TLRs expressed in sperm, including findings from experimental models in mice, humans, and industrial livestock.
The activation of TLR2 and TLR4, which detect Gram-positive and Gram-negative bacteria, has been shown to reduce sperm motility and viability, thereby impairing fertilization. Conversely, low levels of TLR2 activation have been reported to promote the fertilization of bull sperm, suggesting that TLR2/4 may act as regulators of fertilization. TLR7 and TLR8, which are exclusively expressed in X chromosome-bearing sperm (X-sperm), have attracted increasing research interest. These receptors modulate sperm metabolism, selectively reduce the motility of X sperm, and enable the separation of X and Y sperm.
TLRs in the sperm serve as immune receptors that detect bacterial and viral infections, thereby reducing sperm functionality, preventing miscarriage, protecting maternal health, and sex selection.
Toll样受体（TLRs）是先天性免疫系统的关键组成部分，在包括生殖系统在内的各种细胞中均有表达。尽管它们在女性生殖组织如卵巢和子宫中的作用，包括它们在受精和着床中的参与，已被广泛综述，但它们在雄性生殖细胞，特别是精子中的表达和功能仍未得到充分研究。
本综述全面总结了关于精子中表达的TLRs的研究，包括来自小鼠、人类和家畜实验模型的研究结果。
已证明检测革兰氏阳性和革兰氏阴性细菌的TLR2和TLR4的激活会降低精子活力和生存能力，从而损害受精。相反，据报道低水平的TLR2激活可促进公牛精子的受精，这表明TLR2/4可能作为受精的调节因子。专门在携带X染色体的精子（X精子）中表达的TLR7和TLR8已引起越来越多的研究兴趣。这些受体调节精子代谢，选择性降低X精子的活力，并实现X精子和Y精子的分离。
精子中的TLRs作为免疫受体，可检测细菌和病毒感染，从而降低精子功能、预防流产、保护母体健康并进行性别选择。
