Expression and localisation of RXFP3 in human spermatozoa and impact of INSL7 on sperm functions

Heidari, Somaye; Taromchi, Amir Hossein; Nejatbakhsh, Reza; Shokri, Saeed

doi:10.1111/and.12928

Cited by 6 publications

(2 citation statements)

References 33 publications

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“…Relaxin-1 is also believed to exist as circulatory peptide in the circulation ( Bathgate et al, 2013 ), but the function of the relaxin-1 in humans and higher primates is mostly unclear. Relaxin-3 is the most recently identified member of the relaxin family and is primarily expressed in the brain of mammals ( Heidari et al, 2018 ). In our study, we first tested the vasoactive function of all three relaxins in mouse mesenteric arteries.…”

Section: Discussionmentioning

confidence: 99%

RXFP1 Receptor Activation by Relaxin-2 Induces Vascular Relaxation in Mice via a Gαi2-Protein/PI3Kß/γ/Nitric Oxide-Coupled Pathway

et al. 2018

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Background: Relaxins are small peptide hormones, which are novel candidate molecules that play important roles in cardiometablic syndrome. Relaxins are structurally related to the insulin hormone superfamily, which provide vasodilatory effects by activation of G-protein-coupled relaxin receptors (RXFPs) and stimulation of endogenous nitric oxide (NO) generation. Recently, relaxin could be demonstrated to activate Gi proteins and phosphoinositide 3-kinase (PI3K) pathways in cultured endothelial cells in vitro. However, the contribution of the Gi-PI3K pathway and their individual components in relaxin-dependent relaxation of intact arteries remains elusive.Methods: We used Gαi2- (Gnai2-/-) and Gαi3-deficient (Gnai3-/-) mice, pharmacological tools and wire myography to study G-protein-coupled signaling pathways involved in relaxation of mouse isolated mesenteric arteries by relaxins. Human relaxin-1, relaxin-2, and relaxin-3 were tested.Results: Relaxin-2 (∼50% relaxation at 10-11 M) was the most potent vasodilatory relaxin in mouse mesenteric arteries, compared to relaxin-1 and relaxin-3. The vasodilatory effects of relaxin-2 were inhibited by removal of the endothelium or treatment of the vessels with N (G)-nitro-L-arginine methyl ester (L-NAME, endothelial nitric oxide synthase (eNOS) inhibitor) or simazine (RXFP1 inhibitor). The vasodilatory effects of relaxin-2 were absent in arteries of mice treated with pertussis toxin (PTX). They were also absent in arteries isolated from Gnai2-/- mice, but not from Gnai3-/- mice. The effects were not affected by FR900359 (Gαq protein inhibitor) or PI-103 (PI3Kα inhibitor), but inhibited by TGX-221 (PI3Kβ inhibitor) or AS-252424 (PI3Kγ inhibitor). Simazine did not influence the anti-contractile effect of perivascular adipose tissue.Conclusion: Our data indicate that relaxin-2 produces endothelium- and NO-dependent relaxation of mouse mesenteric arteries by activation of RXFP1 coupled to Gi2-PI3K-eNOS pathway. Targeting vasodilatory Gi-protein-coupled RXFP1 pathways may provide promising opportunities for drug discovery in endothelial dysfunction and cardiometabolic disease.

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Section: Discussionmentioning

confidence: 99%

RXFP1 Receptor Activation by Relaxin-2 Induces Vascular Relaxation in Mice via a Gαi2-Protein/PI3Kß/γ/Nitric Oxide-Coupled Pathway

et al. 2018

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“…Ou et al (2020) carried out a transcriptome analysis on spermatogonial stem cells (SSCs) and reported that LRRC34 was highly expressed in mouse SSCs and was essential for in vitro SSC proliferation. RXFP3 was identified to be differentially expressed in human sperm and was likely diminished in spermiogenesis (Heidari et al, 2018). Furthermore, other studies suggested PPP2R2B and PCK1 as candidate genes affecting the semen quality traits in livestock (Huang et al, 2016;Gao et al, 2019).…”

Section: Genome-wide Association Studiesmentioning

confidence: 98%

Genetic and Genomic Analyses of Service Sire Effect on Female Reproductive Traits in Holstein Cattle

et al. 2021

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Fertility and reproductive performance are key drivers of dairy farm profitability. Hence, reproduction traits have been included in a large majority of worldwide dairy cattle selection indexes. The reproductive traits are lowly heritable but can be improved through direct genetic selection. However, most scientific studies and dairy cattle breeding programs have focused solely on the genetic effects of the dam (GED) on reproductive performance and, therefore, ignored the contribution of the service sire in the phenotypic outcomes. This study aimed to investigate the service sire effects on female reproductive traits in Holstein cattle from a genomic perspective. Genetic parameter estimation and genome-wide association studies (GWAS) were performed for the genetic effect of service sire (GESS) on conception rate (CR), 56-day non-return rate (NRR56), calving ease (CE), stillbirth (SB), and gestation length (GL). Our findings indicate that the additive genetic effects of both sire and dam contribute to the phenotypic variance of reproductive traits measured in females (0.0196 vs. 0.0109, 0.0237 vs. 0.0133, 0.0040 vs. 0.0289, 0.0782 vs. 0.0083, and 0.1024 vs. 0.1020 for GESS and GED heritability estimates for CR, NRR56, CE, SB, and GL, respectively), and these two genetic effects are positively correlated for SB (0.1394) and GL (0.7871). Interestingly, the breeding values for GESS on insemination success traits (CR and NRR56) are unfavorably and significantly correlated with some production, health, and type breeding values (ranging from −0.449 to 0.274), while the GESS values on calving traits (CE, SB, and GL) are usually favorably associated with those traits (ranging from −0.493 to 0.313). One hundred sixty-two significant single-nucleotide polymorphisms (SNPs) and their surrounding protein-coding genes were identified as significantly associated with GESS and GED, respectively. Six genes overlapped between GESS and GED for calving traits and 10 genes overlapped between GESS for success traits and calving traits. Our findings indicate the importance of considering the GESS when genetically evaluating the female reproductive traits in Holstein cattle.

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Maternal Fed Zinc-Deficient Diet: Effects on Relaxin Family Peptides and Oxidant System in the Testis and Liver Tissue of Male Offspring

Kose,

Sivrikaya,

Menevse

2024

Biol Trace Elem Res

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Today, the studies are limited on roles of insulin-like peptide 3 (INSL3), insulin-like peptide 7 (INSL7), and relaxin family peptide receptor 1 (RXFP1) which are synthesized by the testis. It is aimed to investigate the levels of the sex hormone as testosterone and the family of insulin-like proteins (relaxin family peptides), which are important in the puberty transition, in the testicular and liver tissues of male offspring born to female rats fed a zinc-deficient diet during the pregnancy, and in the changes in lipid peroxidation markers. The study was performed on 40 male offspring. In Group I: Control group, both male offspring and mothers were fed with standard rat chow. In Group II: Zinc deficient diet, both male offspring and mothers were fed a zinc-deficient diet (2.8 mg/kg zinc). In Group III: Normal diet, male offspring fed standard rat chow for 45 days (66th day) after being separated from their mothers with a maternal zinc-deficient diet. In Group IV: Zinc-supplemented diet, offspring fed with zinc supplemented (5 mg/kg/day intraperitoneal zinc sulfate, i.p.) in addition to standard rat chow after being separated from their mothers with maternal zinc deficiency until the termination of the study (66th day). Our study suggests that zinc-supplemented diets play an important role in the changes in INSL3, INSL7, RXFP1, and testosterone levels during spermatogenesis. INSL7, INSL3, and RXFP1 levels were higher in zinc-supplemented group than the zinc-deficient diet group. Liver levels of INSL3, INSL7, and MDA were significantly different in zinc-deficiency diet group than zinc-supplemented group.

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Expression and localisation of RXFP3 in human spermatozoa and impact of INSL7 on sperm functions

Cited by 6 publications

References 33 publications

RXFP1 Receptor Activation by Relaxin-2 Induces Vascular Relaxation in Mice via a Gαi2-Protein/PI3Kß/γ/Nitric Oxide-Coupled Pathway

RXFP1 Receptor Activation by Relaxin-2 Induces Vascular Relaxation in Mice via a Gαi2-Protein/PI3Kß/γ/Nitric Oxide-Coupled Pathway

Genetic and Genomic Analyses of Service Sire Effect on Female Reproductive Traits in Holstein Cattle

Maternal Fed Zinc-Deficient Diet: Effects on Relaxin Family Peptides and Oxidant System in the Testis and Liver Tissue of Male Offspring

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