Semen Components Differentially Regulate Endometrial and Systemic Immune Responses in Goats: Molecular Evidence from Ex Vivo and In Vivo Models

The interaction between semen and the female reproductive tract is a critical step in fertilization and pregnancy establishment. In most mammals, insemination induces a transient inflammatory response in the uterus, but the specific semen constituent(s) responsible remain unclear. Using ex vivo and in vivo caprine models, we examined whether sperm and seminal plasma (SP) differentially regulate endometrial and systemic immune responses. Goat endometrial explants were co-cultured with increasing concentrations of sperm or SP for 0, 1, 3, or 6 h. Viable sperm and SP, but not heat-inactivated sperm, induced a rapid, dose-dependent, and transient pro-inflammatory response characterized by increased expression of TNFA, IL-1B, IL-6, and IL-8, together with reduced IL-4 and IL-10 transcript abundance. In vivo, estrus-synchronized nanny goats mated with fertile bucks showed time-dependent changes in serum cytokines and a pro-inflammatory response in peripheral blood cells, whereas non-mated controls showed no comparable changes. Mechanistically, semen exposure was associated with a selective increase in TLR2 mRNA expression in the endometrium, with only minor changes in TLR4, suggesting that TLR2 may contribute to semen-induced uterine immune activation in goats. Collectively, these findings indicate that semen constituents can prime the caprine endometrium toward a pro-inflammatory state and are consistent with a potential role for TLR2-associated signaling in reproductive tract immune modulation.