Semen Components Differentially Regulate Endometrial and Systemic Immune Responses in Goats: Molecular Evidence from Ex Vivo and In Vivo Models
9 affiliations
- 1Division of Animal Sciences, University of Missouri, Columbia, 65211 MO, USA
- 2Department of Theriogenology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt
- 3Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia
- 4Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
- 5Department of Animal Health and Poultry, Animal and Poultry Production Division, Desert Research Center (DRC), Cairo 11753, Egypt
- 6Department of Development of Animal Wealth, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt
- 7Biology Department, College of Science and Humanities, Prince Sattam bin Abdulaziz University, P.O. Box 83, Al-Kharj 11940, Saudi Arabia
- 8Department of Clinical Sciences, College of Veterinary Medicine, King Faisal University, P.O. Box 400, Al-Ahsa 31982, Saudi Arabia
- 9Future-Leading and Advanced Graduate-Schools (FLAGs), Hiroshima University, Higashi-Hiroshima, 739-8514, Japan
Abstract
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.
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BibTeX
@article{ezz2026semen,
title = {{Semen Components Differentially Regulate Endometrial and Systemic Immune Responses in Goats: Molecular Evidence from Ex Vivo and In Vivo Models}},
author = {Mohamed Aboul Ezz and Haifa Ali Alqhtani and Huda A. Alqahtani and Ahmed El-Sayed and Ahmed Ateya and Asmaa Darwish and Fatmah A. Safhi and Elham Mohammed Alzahrani and Tahani M. I. Al-Hazani and Mohamed Marzok and Abdelmonem Montaser and Akio Miyamoto},
journal = {Biomolecules},
year = {2026},
month = oct,
doi = {10.3390/biom16111541},
url = {https://www.mdpi.com/2218-273X/16/11/1541},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Semen Components Differentially Regulate Endometrial and Systemic Immune Responses in Goats: Molecular Evidence from Ex Vivo and In Vivo Models
AU - Mohamed Aboul Ezz
AU - Haifa Ali Alqhtani
AU - Huda A. Alqahtani
AU - Ahmed El-Sayed
AU - Ahmed Ateya
AU - Asmaa Darwish
AU - Fatmah A. Safhi
AU - Elham Mohammed Alzahrani
AU - Tahani M. I. Al-Hazani
AU - Mohamed Marzok
AU - Abdelmonem Montaser
AU - Akio Miyamoto
PY - 2026
DA - 2026/10/22
JO - Biomolecules
DO - 10.3390/biom16111541
UR - https://www.mdpi.com/2218-273X/16/11/1541
AB - 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.
SN - 2218-273X
ER -