Oral Presentation ESA-SRB 2023 in conjunction with ENSA

Sperm participate in modulating the cervical epithelial cell immune response to seminal fluid (#141)

David J Sharkey 1 , Hannah E Lyons 1 , Sarah A Robertson 1
  1. Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, South Australia, Australia

Seminal fluid introduced into the female reproductive tract at coitus induces an inflammation-like response within the cervical tissues of women. The response involves induction of cytokines and chemokines to drive leukocyte recruitment and activation, that in turn promote embryo implantation and establish immune tolerance towards male allo-antigens. Soluble factors in seminal plasma are important mediators of seminal fluid signalling. Recently we showed in mice that sperm facilitate the female response – but whether sperm also contribute in women is unclear. In this study, we tested the hypothesis that human sperm interact with Ect1 cervical epithelial cells to induce cytokine production in vitro. Nine normozoospermic men (according to WHO VI guidelines) of reproductive age men provided semen samples for the study. Ect1 cells were incubated with 10% (v/v) whole semen, 10% seminal plasma, 10% washed sperm, or washed sperm at fixed concentrations of 1, 5, and 10M/ml, then cytokine secretion was assessed in 24hr supernatants by multiplex microbead assay. Electron microscopy was utilised to visualize physical interactions between sperm and Ect1 cells. Washed sperm - as well as whole semen and seminal plasma – acted to increase Ect1 cell CSF2, CXCL8, IL1B and IL6 cytokine production (n=9, all P < 0.01), with sperm-mediated induction occurring in a dose-dependent manner for CSF2, CXCL8 and IL1B (n=9, all P < 0.02). Electron microscopy showed evidence of sperm head attachment to microvilli on the Ect1 cell surface, and in some instances, full engulfment by Ect1 cells. This data shows that human sperm interact closely with cervical epithelial cells and act to modulate their cytokine production. Understanding the mechanisms that mediate this interaction will progress understanding of biological processes by which maternal immune tolerance is generated, and may aid in the development of interventions that improve immune receptivity to embryo implantation.