Expression of LGR7 in the Primate Corpus Luteum Implicates the Corpus Luteum as a Relaxin Target Organ

Maseelall, Priya; Seungdamrong, Aimee; Weiss, Gerson; Wojtczuk, Andrea; Donnelly, R. B.; Stouffer, Richard L.; Goldsmith, Laura T.

doi:10.1111/j.1749-6632.2009.03946.x

Cited by 11 publications

(5 citation statements)

References 11 publications

(19 reference statements)

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“…Furthermore, we analyzed the presence of relaxin and its receptors at the protein levels in both oocytes and embryos. Ovarian follicular and corpora lutea cells were used as positive controls as already reported in previous studies [ 11 , 15 , 16 , 25 , 34 - 36 ]. Here, we used anti-human relaxin and RXFP1/2, whose antigenic regions were found to be highly similar among various mammalians (cattle, chimpanzee, dog, horse, human, and mice).…”

Section: Discussionmentioning

confidence: 99%

Examination of relaxin and its receptors expression in pig gametes and embryos

Feugang

Rodríguez-Muñoz

Willard

et al. 2011

Reprod Biol Endocrinol

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BackgroundRelaxin is a small peptide also known as pregnancy hormone in many mammals. It is synthesized by both male and female tissues, and its secretions are found in various body fluids such as plasma serum, ovarian follicular fluid, utero-oviduct secretions, and seminal plasma of many mammals, including pigs. However, the presence and effects of relaxin in porcine gametes and embryos are still not well-known. The purpose of this study was to assess the presence of relaxin and its receptors RXFP1 and RXFP2 in pig gametes and embryos.MethodsImmature cumulus-oocyte complexes (COCs) were aspirated from sows' ovaries collected at the abattoir. After in vitro-maturation, COCs were in vitro-fertilized and cultured. For studies, immature and mature COCs were separately collected, and oocytes were freed from their surrounding cumulus cells. Denuded oocytes, cumulus cells, mature boar spermatozoa, zygotes, and embryos (cleaved and blastocysts) were harvested for temporal and spatial gene expression studies. Sections of ovary, granulosa and neonatal porcine uterine cells were also collected to use as controls.ResultsUsing both semi-quantitative and quantitative PCRs, relaxin transcripts were not detected in all tested samples, while RXFP1 and RXFP2 mRNA were present. Both receptor gene products were found at higher levels in oocytes compared to cumulus cells, irrespective of the maturation time. Cleaved-embryos contained higher levels of RXFP2 mRNA, whereas, blastocysts were characterized by a higher RXFP1 mRNA content. Using western-immunoblotting or in situ immunofluorescence, relaxin and its receptor proteins were detected in all samples. Their fluorescence intensities were consistently more important in mature oocytes than immature ones. The RXFP1 and RXFP2 signal intensities were mostly located in the plasma membrane region, while the relaxin ones appeared homogeneously distributed within the oocytes and embryonic cells. Furthermore, spermatozoa displayed stronger RXFP2 signal than RXFP1 after western-immunoblotting.ConclusionAll together, our findings suggest potential roles of relaxin and its receptors during oocyte maturation, early embryo development, and beyond.

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Section: Discussionmentioning

confidence: 99%

Examination of relaxin and its receptors expression in pig gametes and embryos

Feugang

Rodríguez-Muñoz

Willard

et al. 2011

Reprod Biol Endocrinol

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“…38 Relaxin is also produced by the theca interna cells of follicles, 39 which are likely to be the primary contributors of the relaxin detected in follicular fluid. 40 RXFP1 messenger RNA (mRNA) has been detected in the corpus luteum of humans and monkeys 41 and specifically on granulosa and cumulus cells of pig antral follicles 42 and potentially in human granulosa cells of primordial, primary, and secondary follicles. 43 A variety of studies have suggested that circulating relaxin reaches its peak in the latter half of the luteal phase of the menstrual cycle with levels either low or nondetectable in other cycle stages.…”

Section: Expression Of Relaxin and Relaxin Receptors (Rxfp1) During The Menstrual Cyclementioning

confidence: 99%

The Role of Relaxin in Normal and Abnormal Uterine Function During the Menstrual Cycle and Early Pregnancy

et al. 2017

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The hormone relaxin is a 6-kDa peptide with high structural similarity to insulin. It is primarily produced by the corpus luteum during pregnancy but is also synthesized by other reproductive organs such as the uterus, decidua, and placenta. Relaxin binds to its receptor RXFP1, which has been localized to a wide variety of reproductive and nonreproductive tissues. The peptide's many uterotropic effects include stimulating uterine growth and vascularization, remodeling extracellular matrix components, and regulating vascular endothelial growth factor in preparation for implantation. Evidence also supports a role for relaxin in the systemic maternal vascular adaptations required for a healthy pregnancy. Diminished relaxin levels in early pregnancy are linked with increased risks of miscarriage and the development of preeclampsia. In addition to pregnancy, relaxin may also play a functional role in the uterus during the menstrual cycle, and modified relaxin activity may contribute to gynecological disorders such as uterine fibrosis and endometriosis. Despite over 75 years of research, we still have a limited understanding of relaxin's broad roles in the uterus, particularly as there are significant species differences in its synthesis and activity, which restricts the use of animal models for human-centric questions. Here, we review current knowledge regarding relaxin actions in the human uterus during the menstrual cycle and in early pregnancy, with a focus on its potential roles in various gynecological disorders, as well as the pregnancy disorders such as preeclampsia, recurrent miscarriage, and early pregnancy loss.

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“…Thus, steroid/P control of steroidogenic genes may be limited in the CL of SEP. There is evidence for regulation of primate luteal function by non-steroidal targets of CG such as prostaglandins (Bogan et al, 2008a), luteal relaxin production (Maseelall et al, 2009) and modulation of luteal cytokines (Townson and Liptak, 2003). All of these local factors were altered by CG, as noted in our previous microarray analysis (Bishop et al, 2011b), and may regulate more probesets than steroids alone.…”

Section: Discussionmentioning

confidence: 99%

Effects of steroid ablation and progestin replacement on the transcriptome of the primate corpus luteum during simulated early pregnancy

Bishop

Aazzerah

Quennoz

et al. 2013

MHR: Basic Science of Reproductive Medicine

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Previous microarray analyses indicated that a portion of the transcriptome in the macaque corpus luteum (CL) of the menstrual cycle was regulated indirectly by luteinizing hormone via the local actions of steroid hormones, notably progesterone (P). The current study was designed to investigate this concept in the CL of early pregnancy by analyzing chorionic gonadotrophin (CG)-regulated genes that are dependent versus independent of local steroid action. Exogenous human chorionic gonadotropin treatment simulating early pregnancy (SEP) began on Day 9 of the luteal phase in female rhesus monkeys with and without concurrent administration of the 3-β-hydroxysteroid dehydrogenase inhibitor trilostane (TRL) with or without the synthetic progestin R5020. Compared with SEP treatment alone, TRL altered 50 mRNA transcripts on Day 10, rising to 95 on Day 15 (P<0.05, ≥2-fold change in gene expression). Steroid-sensitive genes were validated; notably effects of steroid ablation and P replacement varied by day. Expression of some genes previously identified as P-regulated in the macaque CL during the menstrual cycle were not significantly altered by steroid ablation and P replacement during CG exposure in SEP. These data indicate that the majority of CG-regulated luteal transcripts are differentially expressed independently of local steroid actions. However, the steroid-regulated genes in the macaque CL may be essential during early pregnancy, based on previous reports that TRL treatment initiates premature structural regression of the CL during SEP. These data reinforce the concept that the structure, function and regulation of the rescued CL in early pregnancy differs from the CL of the menstrual cycle in primates.

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Expression of LGR7 in the Primate Corpus Luteum Implicates the Corpus Luteum as a Relaxin Target Organ

Cited by 11 publications

References 11 publications

Examination of relaxin and its receptors expression in pig gametes and embryos

Examination of relaxin and its receptors expression in pig gametes and embryos

The Role of Relaxin in Normal and Abnormal Uterine Function During the Menstrual Cycle and Early Pregnancy

Effects of steroid ablation and progestin replacement on the transcriptome of the primate corpus luteum during simulated early pregnancy

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