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Type: Journal article
Title: Interferon-gamma inhibits seminal plasma induction of colony stimulating factor 2 in mouse and human reproductive tract epithelial cells
Author: Sharkey, D.
Glynn, D.
Schjenken, J.
Tremellen, K.
Robertson, S.
Citation: Biology of Reproduction, 2018; 99(3):514-526
Publisher: Oxford University Press
Issue Date: 2018
ISSN: 0006-3363
Statement of
David J. Sharkey, Danielle J. Glynn, John E. Schjenken, Kelton P. Tremellen and Sarah A. Robertson
Abstract: Seminal fluid interacts with the female reproductive tract to initiate a permissive immune response that facilitates embryo implantation and pregnancy success. The immune-regulatory cytokine interferon-γ (IFNG), which can be elevated in seminal plasma and is associated with reduced fertility. Here we investigated how IFNG influences the female immune response to seminal fluid. In human Ect1 cervical epithelial cells, IFNG added at physiologically relevant concentrations substantially impaired seminal plasma-induced synthesis of key cytokines colony stimulating factor 2 (CSF2) and interleukin-6 (IL6). Seminal fluid-induced CSF2 synthesis was also suppressed in the uterus of mice in vivo, when IFNG was delivered transcervically 12 h after mating. Transforming growth factor B1 (TGFB1) is the major seminal fluid signaling factor which elicits CSF2 induction, and IFNG exhibited potent dose-dependent suppression of CSF2 synthesis induced by TGFB1 in murine uterine epithelial cells in vitro. Similarly, IFNG suppressed TGFB1-mediated CSF2 induction in Ect1 cells and human primary cervical epithelial cells, however IL6 regulation by IFNG was independent of TGFB1. qPCR confirmed CSF2 regulation by IFNG in Ect1 cells occurs at the gene transcription level, secondary to IFNG suppression of TGFBR2 encoding TGFB receptor-2. Conversely TGFB1 suppressed IFNG receptor genes IFNGR1 and IFNGR2. These data identify IFNG as a potent inhibitor of the TGFB-mediated seminal fluid interaction with relevant reproductive tract epithelia in mice and human. These findings raise the prospect that IFNG in the male partner's seminal fluid impairs immune adaptation for pregnancy following coitus in women.
Keywords: Female reproductive tract; immunology; cytokines; cervix; uterus; seminal plasma
Description: Advance Access Publication Date: 27 March 2018
Rights: © The Author(s) 2018. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved.
RMID: 0030084533
DOI: 10.1093/biolre/ioy071
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Appears in Collections:Obstetrics and Gynaecology publications

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