ArticlePloS one2019
TLR2/4 signaling pathway mediates sperm-induced inflammation in bovine endometrial epithelial cells in vitro.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 63 citations in OpenAlex.
- The maternal immune response to semen: implications for reproductive success in livestock.Reproduction & fertility · 2026Review
- Investigating the role of the bacterial metabolite ectoine on immune regulation within the bovine female reproductive tract.Journal of animal science · 2026Article
- Seminal fluid effects on female reproductive function in laboratory, livestock, and domestic species.The Journal of reproduction and development · 2026Review
- Innate immune system for a crosstalk of sperm-egg-uterine epithelium towards fertility: Toll-like receptor 2 as a physiological sensor.The Journal of reproduction and development · 2026Review
- Environmental influences on seminal plasma: Molecular and functional insights.The Journal of reproduction and development · 2026Review
- Time- and dose-dependent activation of the NLRP3 and MyD88/NF-κB pathways by Trueperella pyogenes membrane vesicles in bovine endometrial epithelial cells.Veterinary research · 2025Article
- TLR2 and TLR4 bridge physiological and pathological inflammation in the reproductive system.Communications biology · 2025Review
- Semen extender triggers a mild physiological inflammatory response in the uterus without disrupting sperm-uterine immune crosstalk in vitro in cattle.The Journal of reproduction and development · 2025Article
- Peptidoglycan derived fromFrontiers in immunology · 2025Article
- Platelet secretions exert anti-inflammatory effectsFrontiers in immunology · 2025Article
- Single-strain probiotics enhance growth, anti-pathogen immunity, and resistance to Nocardia seriolae in grey mullet (Mugil cephalus) via gut microbiota modulation.Animal microbiome · 2024Article
- Effects of administration of mycobacterium cell wall fraction during the periovulatory period on embryo development following superovulation in virgin dairy heifers.JDS communications · 2024Article
- Homology Modeling, Molecular Dynamics Simulation, and Prediction of Bovine TLR2 Heterodimerization.International journal of molecular sciences · 2024Article
- Sperm hyperactivation in the uterus and oviduct: a double-edged sword for sperm and maternal innate immunity toward fertility.Animal reproduction · 2024Review
- The transcriptomic response of bovine uterine tissue is altered in response to sperm from high- and low-fertility bulls†.Biology of reproduction · 2023Article
- Sperm induce proinflammatory responses in the uterus and peripheral blood immune cells of artificially inseminated cows.The Journal of reproduction and development · 2023Article
- Acquisition of Immune Privilege in GBM Tumors: Role of Prostaglandins and Bile Salts.International journal of molecular sciences · 2023Article
- Activation of sperm Toll-like receptor 2 induces hyperactivation to enhance the penetration to mucus and uterine glands: a trigger for the uterine inflammatory cascade in cattle.Frontiers in immunology · 2023Article
- Hyaluronan regulates sperm-induced inflammatory response by enhancing sperm attachment to bovine endometrial epithelial cellsFrontiers in endocrinology · 2023Article
- Sperm activate TLR2/TLR1 heterodimerization to induce a weak proinflammatory response in the bovine uterus.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have recently shown that sperm attachment to bovine endometrial epithelial cells (BEECs) triggers uterine local innate immunity with induction of a pro-inflammatory response in vitro, however details of the mechanism remain unknown. Here, we investigated the involvement of Toll-like receptor 2/4 (TLR2/4) pathway in mediating sperm-BEECs inflammatory process. Immunohistochemistry of the uterine tissue revealed that TLR2 and TLR4 proteins were present in the luminal and glandular epithelia of bovine endometrium. Moreover, BEECs monolayers were treated with TLR2 agonist (Pam; 0, 10, 100, and 1000 ng/ml) or TLR4 agonist (LPS; 0, 0.1, 1, and 10 ng/ml) for 0, 1, 3, or 6 h, followed by evaluating mRNA expression of the pro-inflammatory genes (TNFA, IL-1B, IL-8, and PGES) in BEECs using a real-time PCR. Both Pam and LPS treatments showed a dose-dependent stimulation of mRNA expression of the pro-inflammatory genes. To elucidate the functional role of TLR2/4 in sperm-BEECs interaction, BEECs monolayers were incubated with either TLR2 antagonist or TLR4 antibody for 2 h prior to the co-culture with sperm for 3 h. Importantly, pre-incubation of BEECs with TLR2 antagonist or TLR4 antibody prevented the stimulatory effect of sperm on the transcription of pro-inflammatory genes in BEECs. Furthermore, sperm increased the phosphorylation levels of TLR2/4 downstream targets (p38MAPK and JNK) in BEECs within 1 h of the co-culture. Treatment of BEECs with TLR2 antagonist prior to sperm addition inhibited JNK phosphorylation, while TLR4 antibody inhibited the phosphorylation of both p38MAPK and JNK. In conclusion, the present in vitro findings strongly suggest that bovine endometrial epithelial cells respond to sperm via TLR2/4 signal transduction.
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