# Toll-like Receptor Expression Patterns in the Female Reproductive Tract of Sheep

## TL;DR

This study explores how immune system proteins called Toll-like receptors are linked to fertility in sheep, finding differences in their levels between high- and low-fertility animals.

## Contribution

The study identifies specific Toll-like receptors (TLR2, TLR6, TLR7) as potential regulators of fertility in sheep, linking immune function to reproductive outcomes.

## Key findings

- TLR2, TLR6, and TLR7 are expressed in key reproductive tissues of sheep, with distinct patterns.
- High-prolificacy sheep show altered TLR2, TLR6, and TLR7 expression compared to low-prolificacy sheep.
- TLR7 is associated with granulosa cell apoptosis, suggesting a role in follicular development.

## Abstract

Fertility in farm animals is critical for agricultural productivity, yet we do not fully understand all the biological factors that control it. Our immune system contains special proteins called Toll-like receptors that normally help defend against infections, but they might also play unexpected roles in reproduction. We examined these receptors in the reproductive organs of Hu sheep, a breed known for having multiple lambs per pregnancy. We discovered that these immune receptors are present throughout the female reproductive system, with three specific types showing interesting patterns. Remarkably, sheep that typically produce more lambs had different amounts of these receptors compared to those producing fewer lambs. One receptor type was found near dying cells in the ovaries, suggesting it might help control egg development. This research reveals a surprising connection between the immune system and fertility in sheep. Understanding this relationship could potentially help farmers improve breeding programs and address fertility problems in livestock, ultimately contributing to more sustainable and productive agriculture. Our findings open new possibilities for enhancing reproductive efficiency in sheep through methods that influence immune function.

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.