Abstract
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.
Highlights
In the female mammal the peptide hormone relaxin is secreted into the circulation principally from the ovary and, during pregnancy, probably from the endometrium and placenta (Sherwood, 1994; Ivell and Einspanier, 2002)
In mice, based on their expression of relaxin mRNA, the main sources would appear to be in descending order: epididymis, prostate, testis, seminal vesicles and vas deferens, with coagulating and preputial glands having only trace amounts of specific mRNA (Figure 1)
Our results are very similar to those presented by Ganesan et al (2009), who indicated low but variable expression of prostate relaxin mRNA for C57BL/6 mice
Summary
In the female mammal the peptide hormone relaxin is secreted into the circulation principally from the ovary and, during pregnancy, probably from the endometrium and placenta (Sherwood, 1994; Ivell and Einspanier, 2002). It may be expressed as a paracrine hormone in some organs, including the heart (Taylor and Clark, 1994). In terms of functionality in the male, paracrine roles have been suggested within the prostate gland and in the context of prostate carcinoma (Ivell et al, 2011). There is some evidence to suggest that relaxin may act directly on spermatozoa, thereby improving fertilization rates, at least in vitro (Miah et al, 2006; Ferlin et al, 2012)
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