Sperm modulate uterine immune parameters relevant to embryo implantation and reproductive success in mice

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dc.contributor.authorSchjenken, J.E.
dc.contributor.authorSharkey, D.J.
dc.contributor.authorGreen, E.S.
dc.contributor.authorChan, H.Y.
dc.contributor.authorMatias, R.A.
dc.contributor.authorMoldenhauer, L.M.
dc.contributor.authorRobertson, S.A.
dc.date.issued2021
dc.description.abstractSeminal fluid factors modulate the female immune response at conception to facilitate embryo implantation and reproductive success. Whether sperm affect this response has not been clear. We evaluated global gene expression by microarray in the mouse uterus after mating with intact or vasectomized males. Intact males induced greater changes in gene transcription, prominently affecting pro-inflammatory cytokine and immune regulatory genes, with TLR4 signaling identified as a top-ranked upstream driver. Recruitment of neutrophils and expansion of peripheral regulatory T cells were elevated by seminal fluid of intact males. In vitro, epididymal sperm induced IL6, CXCL2, and CSF3 in uterine epithelial cells of wild-type, but not Tlr4 null females. Collectively these experiments show that sperm assist in promoting female immune tolerance by eliciting uterine cytokine expression through TLR4-dependent signaling. The findings indicate a biological role for sperm beyond oocyte fertilization, in modulating immune mechanisms involved in female control of reproductive investment.
dc.description.statementofresponsibilityJohn E. Schjenken, David J. Sharkey, Ella S. Green, Hon Yeung Chan, Ricky A. Matias, Lachlan M. Moldenhauer and Sarah A. Robertson
dc.identifier.citationCommunications Biology, 2021; 4(1):1-14
dc.identifier.doi10.1038/s42003-021-02038-9
dc.identifier.issn2399-3642
dc.identifier.issn2399-3642
dc.identifier.orcidSchjenken, J.E. [0000-0001-6293-6160]
dc.identifier.orcidSharkey, D.J. [0000-0002-4831-7950]
dc.identifier.orcidGreen, E.S. [0000-0002-3009-3442]
dc.identifier.orcidChan, H.Y. [0000-0001-9841-2094]
dc.identifier.orcidMoldenhauer, L.M. [0000-0002-3141-2521]
dc.identifier.orcidRobertson, S.A. [0000-0002-9967-0084]
dc.identifier.urihttps://hdl.handle.net/2440/133754
dc.language.isoen
dc.publisherSpringer Nature
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1041335
dc.relation.granthttp://purl.org/au-research/grants/arc/DP160102366
dc.relation.granthttp://purl.org/au-research/grants/arc/DP190103694
dc.rightsThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.source.urihttps://doi.org/10.1038/s42003-021-02038-9
dc.subjectImmune tolerance; infertility; inflammation; preclinical research
dc.subject.meshUterus
dc.subject.meshEndometrium
dc.subject.meshSpermatozoa
dc.subject.meshAnimals
dc.subject.meshMice, Inbred C57BL
dc.subject.meshMice, Inbred CBA
dc.subject.meshMice
dc.subject.meshCytokines
dc.subject.meshVasectomy
dc.subject.meshCell Communication
dc.subject.meshSignal Transduction
dc.subject.meshImmune Tolerance
dc.subject.meshReproduction
dc.subject.meshEmbryo Implantation
dc.subject.meshFemale
dc.subject.meshMale
dc.subject.meshT-Lymphocytes, Regulatory
dc.titleSperm modulate uterine immune parameters relevant to embryo implantation and reproductive success in mice
dc.typeJournal article
pubs.publication-statusPublished

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