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High fat diet alters male seminal plasma composition to impair female immune adaptation for pregnancy in mice

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dc.contributor.authorSchjenken, J.E.
dc.contributor.authorMoldenhauer, L.M.
dc.contributor.authorSharkey, D.J.
dc.contributor.authorChan, H.Y.
dc.contributor.authorChin, P.Y.
dc.contributor.authorFullston, T.
dc.contributor.authorMcPherson, N.O.
dc.contributor.authorRobertson, S.A.
dc.date.issued2021
dc.description.abstractPaternal experiences and exposures before conception can influence fetal development and offspring phenotype. The composition of seminal plasma contributes to paternal programming effects through modulating the female reproductive tract immune response after mating. To investigate whether paternal obesity affects seminal plasma immune-regulatory activity, C57Bl/6 male mice were fed an obesogenic high-fat diet (HFD) or control diet (CD) for 14 weeks. Although HFD consumption caused only minor changes to parameters of sperm quality, the volume of seminal vesicle fluid secretions was increased by 65%, and the concentrations and total content of immune-regulatory TGF-β isoforms were decreased by 75% to 80% and 43% to 55%, respectively. Mating with BALB/c females revealed differences in the strength and properties of the postmating immune response elicited. Transcriptional analysis showed >300 inflammatory genes were similarly regulated in the uterine endometrium by mating independently of paternal diet, and 13 were dysregulated by HFD-fed compared with CD-fed males. Seminal vesicle fluid factors reduced in HFD-fed males, including TGF-β1, IL-10, and TNF, were among the predicted upstream regulators of differentially regulated genes. Additionally, the T-cell response induced by mating with CD-fed males was blunted after mating with HFD-fed males, with 27% fewer CD4+ T cells, 26% fewer FOXP3+CD4+ regulatory T cells (Treg) cells, and 19% fewer CTLA4+ Treg cells, particularly within the NRP1+ thymic Treg cell population. These findings demonstrate that an obesogenic HFD alters the composition of seminal vesicle fluid and impairs seminal plasma capacity to elicit a favorable pro-tolerogenic immune response in females at conception.
dc.description.statementofresponsibilityJohn E Schjenken, Lachlan M Moldenhauer, David J Sharkey, Hon Y Chan, Peck Y Chin, Tod Fullston ... et al.
dc.identifier.citationEndocrinology, 2021; 162(10):1-20
dc.identifier.doi10.1210/endocr/bqab123
dc.identifier.issn0013-7227
dc.identifier.issn1945-7170
dc.identifier.orcidSchjenken, J.E. [0000-0001-6293-6160]
dc.identifier.orcidMoldenhauer, L.M. [0000-0002-3141-2521]
dc.identifier.orcidSharkey, D.J. [0000-0002-4831-7950]
dc.identifier.orcidChan, H.Y. [0000-0001-9841-2094]
dc.identifier.orcidChin, P.Y. [0000-0002-0923-0553]
dc.identifier.orcidFullston, T. [0000-0003-1314-3038]
dc.identifier.orcidMcPherson, N.O. [0000-0002-3492-9403]
dc.identifier.orcidRobertson, S.A. [0000-0002-9967-0084]
dc.identifier.urihttps://hdl.handle.net/2440/133069
dc.language.isoen
dc.publisherThe Endocrine Society
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1041335
dc.relation.granthttp://purl.org/au-research/grants/arc/DP160102366
dc.rights© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
dc.source.urihttps://doi.org/10.1210/endocr/bqab123
dc.subjectObesity; mouse; seminal fluid; Treg cell; cytokine
dc.titleHigh fat diet alters male seminal plasma composition to impair female immune adaptation for pregnancy in mice
dc.typeJournal article
pubs.publication-statusPublished

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