Toll-like receptors in mammalian sperm

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.