Male Seminal Relaxin Contributes to Induction of the Post-mating Cytokine Response in the Female Mouse Uterus
The hormone relaxin is important in female reproduction for embryo implantation, cardiovascular function, and during labor and lactation. Relaxin is also synthesized in males by organs of the male tract. We hypothesized that relaxin might be one component of seminal plasma responsible for eliciting...
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Frontiers Media S.A.
2017-06-01
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| Series: | Frontiers in Physiology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fphys.2017.00422/full |
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| author | Danielle J. Glynn Danielle J. Glynn Kee Heng Darryl L. Russell David J. Sharkey Sarah A. Robertson Ravinder Anand-Ivell Ravinder Anand-Ivell Richard Ivell Richard Ivell |
| author_facet | Danielle J. Glynn Danielle J. Glynn Kee Heng Darryl L. Russell David J. Sharkey Sarah A. Robertson Ravinder Anand-Ivell Ravinder Anand-Ivell Richard Ivell Richard Ivell |
| author_sort | Danielle J. Glynn |
| collection | DOAJ |
| description | The hormone relaxin is important in female reproduction for embryo implantation, cardiovascular function, and during labor and lactation. Relaxin is also synthesized in males by organs of the male tract. We hypothesized that relaxin might be one component of seminal plasma responsible for eliciting the female cytokine response induced in the uterus at mating. When recombinant relaxin was injected into the uterus of wild-type (Rln+/+) mice at estrus, it evoked the production of Cxcl1 mRNA and its secreted protein product CXCL1 in four of eight animals. Mating experiments were then conducted using mice with a null mutation in the relaxin gene (Rln−/− mice). qRT-PCR analysis of mRNA expression in wild-type females showed diminished uterine expression of several cytokine and chemokine genes in the absence of male relaxin. Similar differences were also noted comparing Rln−/− and Rln+/+ females mated to wild-type males. Quantification of uterine luminal fluid cytokine content confirmed that male relaxin provokes the production of CXCL10 and CSF3 in Rln+/+ females. Differences were also seen comparing Rln−/− and Rln+/+ females mated with Rln−/− males for CXCL1, CSF3, and CCL5, implying that endogenous relaxin in females might prime the uterus to respond appropriately to seminal fluid at coitus. Finally, pan-leukocyte CD45 mRNA was increased in wild-type matings compared to other combinations, implying that male and female relaxin may trigger leukocyte expansion in the uterus. We conclude that male and/or female relaxin may be important in activating the uterine cytokine/chemokine network required to initiate maternal immune adaptation to pregnancy. |
| first_indexed | 2024-04-13T02:18:46Z |
| format | Article |
| id | doaj.art-0478aa2622d54f56bc3eb9c649e94780 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-04-13T02:18:46Z |
| publishDate | 2017-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-0478aa2622d54f56bc3eb9c649e947802022-12-22T03:07:04ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2017-06-01810.3389/fphys.2017.00422269515Male Seminal Relaxin Contributes to Induction of the Post-mating Cytokine Response in the Female Mouse UterusDanielle J. Glynn0Danielle J. Glynn1Kee Heng2Darryl L. Russell3David J. Sharkey4Sarah A. Robertson5Ravinder Anand-Ivell6Ravinder Anand-Ivell7Richard Ivell8Richard Ivell9Robinson Research Institute and School of Biological Sciences, University of AdelaideAdelaide, SA, AustraliaRobinson Research Institute and Adelaide Medical School, University of AdelaideAdelaide, SA, AustraliaRobinson Research Institute and School of Biological Sciences, University of AdelaideAdelaide, SA, AustraliaRobinson Research Institute and Adelaide Medical School, University of AdelaideAdelaide, SA, AustraliaRobinson Research Institute and Adelaide Medical School, University of AdelaideAdelaide, SA, AustraliaRobinson Research Institute and Adelaide Medical School, University of AdelaideAdelaide, SA, AustraliaSchool of Pharmacy and Medical Sciences, University of South AustraliaAdelaide, SA, AustraliaSchool of Biosciences, University of NottinghamUnited KingdomRobinson Research Institute and School of Biological Sciences, University of AdelaideAdelaide, SA, AustraliaSchool of Biosciences, University of NottinghamUnited KingdomThe hormone relaxin is important in female reproduction for embryo implantation, cardiovascular function, and during labor and lactation. Relaxin is also synthesized in males by organs of the male tract. We hypothesized that relaxin might be one component of seminal plasma responsible for eliciting the female cytokine response induced in the uterus at mating. When recombinant relaxin was injected into the uterus of wild-type (Rln+/+) mice at estrus, it evoked the production of Cxcl1 mRNA and its secreted protein product CXCL1 in four of eight animals. Mating experiments were then conducted using mice with a null mutation in the relaxin gene (Rln−/− mice). qRT-PCR analysis of mRNA expression in wild-type females showed diminished uterine expression of several cytokine and chemokine genes in the absence of male relaxin. Similar differences were also noted comparing Rln−/− and Rln+/+ females mated to wild-type males. Quantification of uterine luminal fluid cytokine content confirmed that male relaxin provokes the production of CXCL10 and CSF3 in Rln+/+ females. Differences were also seen comparing Rln−/− and Rln+/+ females mated with Rln−/− males for CXCL1, CSF3, and CCL5, implying that endogenous relaxin in females might prime the uterus to respond appropriately to seminal fluid at coitus. Finally, pan-leukocyte CD45 mRNA was increased in wild-type matings compared to other combinations, implying that male and female relaxin may trigger leukocyte expansion in the uterus. We conclude that male and/or female relaxin may be important in activating the uterine cytokine/chemokine network required to initiate maternal immune adaptation to pregnancy.http://journal.frontiersin.org/article/10.3389/fphys.2017.00422/fullseminal relaxincytokinesendometrium |
| spellingShingle | Danielle J. Glynn Danielle J. Glynn Kee Heng Darryl L. Russell David J. Sharkey Sarah A. Robertson Ravinder Anand-Ivell Ravinder Anand-Ivell Richard Ivell Richard Ivell Male Seminal Relaxin Contributes to Induction of the Post-mating Cytokine Response in the Female Mouse Uterus Frontiers in Physiology seminal relaxin cytokines endometrium |
| title | Male Seminal Relaxin Contributes to Induction of the Post-mating Cytokine Response in the Female Mouse Uterus |
| title_full | Male Seminal Relaxin Contributes to Induction of the Post-mating Cytokine Response in the Female Mouse Uterus |
| title_fullStr | Male Seminal Relaxin Contributes to Induction of the Post-mating Cytokine Response in the Female Mouse Uterus |
| title_full_unstemmed | Male Seminal Relaxin Contributes to Induction of the Post-mating Cytokine Response in the Female Mouse Uterus |
| title_short | Male Seminal Relaxin Contributes to Induction of the Post-mating Cytokine Response in the Female Mouse Uterus |
| title_sort | male seminal relaxin contributes to induction of the post mating cytokine response in the female mouse uterus |
| topic | seminal relaxin cytokines endometrium |
| url | http://journal.frontiersin.org/article/10.3389/fphys.2017.00422/full |
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