Abstract
In mammals, the uterine mucosal immune system simultaneously recognizes and reacts to most bacteria as well as allogenic sperm mainly through the Toll-like receptors (TLR)2/4 signaling pathway. Here, we characterized the impact of pathogen-derived TLR2/4 ligands (peptidoglycan (PGN)/lipopolysaccharide (LPS)) on the immune crosstalk of sperm with the bovine endometrial epithelium. The real-time PCR analysis showed that the presence of low levels of PGN, but not LPS, blocked the sperm-induced inflammatory responses in bovine endometrial epithelial cells (BEECs) in vitro. Immunoblotting analysis revealed that PGN prevented the sperm-induced phosphorylation of JNK in BEECs. Activation or blockade of the TLR2 system in the endometrial epithelium verified that TLR2 signaling acts as a commonly-shared pathway for PGN and sperm recognition. The impairment of endometrial sperm recognition, induced by PGN, subsequently inhibited sperm phagocytosis by polymorphonuclear neutrophils (PMNs). Moreover, using an ex vivo endometrial explant that more closely resembles those in vivo conditions, showed that sperm provoked a mild and reversible endometrial tissue injury and triggered PMN recruitment into uterine glands, while PGN inhibited these events. Of note, PGN markedly increased the sperm attachment to uterine glands, and relatively so in the surface epithelium. However, addition of the anti-CD44 antibody into a PGN-sperm-explant co-culture completely blocked sperm attachment into glands and surface epithelia, indicating that the CD44 adhesion molecule is involved in the PGN-triggered sperm attachment to the endometrial epithelium. Together, these findings demonstrate that, the presence of PGN residues disrupts sperm immune recognition and prevents the physiological inflammation induced by sperm in the endometrial epithelium via the MyD88-dependent pathway of TLR2 signaling, possibly leading to impairment of uterine clearance and subsequent embryo receptivity.
Highlights
In all mammals, the endometrial mucosa has a unique ability to deal with pathogens, allogeneic spermatozoa, and semi-allogeneic embryos [1,2,3]
To investigate the competitive interaction of PGN/LPS and sperm with endometrial epithelium, bovine endometrial epithelial cells (BEECs) were exposed to PGN/LPS at high (100, and 1000 ng ml−1) or low concentrations
The results showed that co-culturing of sperm with BEECs increased the mRNA expression of inflammatory cytokines (TNFA and IL1B), inflammatory chemokine (IL8), and
Summary
The endometrial mucosa has a unique ability to deal with pathogens, allogeneic spermatozoa, and semi-allogeneic embryos [1,2,3]. Endometrial epithelia express highly conserved specific pattern recognition receptors (PRRs) that can recognize pathogens through pathogen-associated molecular patterns (PAMPs), and tissue injuries through damage-associated molecular patterns (DAMPs) [5]. Among PRRs, Toll-like receptors (TLRs) efficiently recognize virtually all bacteria or their PAMPs, and mount an early immune response, resulting in the expression of inflammatory mediators [6]. Immune cells (mainly polymorphonuclear cells, PMNs) are attracted to the site of infection, ensuring phagocytosis of invading microorganisms or cell fragments [7, 8]. Identifying these early immunological mechanisms in the endometrium during pathophysiological conditions will be paramount for optimal fertility
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
