Identification and characterization of RFRP gene in pigs and its association with reproductive traits

Fang, Ming; Huang, Yueting; Ye, J; Zhang, W; Li, Y; Nie, Qinghua

doi:10.4238/2014.january.14.8

Cited by 10 publications

(6 citation statements)

References 22 publications

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“…Moreover, in birds, GnIH application decreases testosterone release from gonadotropin-stimulated testes in vitro , pointing to a functional role for gonadal GnIH (58). Later, it was shown that RFRP-3 is synthesized in the gonads of all mammals studied to date (59), including humans (60), non-human primates (61), Syrian hamsters (62), mice (60, 63), rats (64), ewe (65), and pigs (66). Across species, the gonads synthesize RFRP-3 and GPR147 (57, 59–61, 63).…”

Section: Rfrp-3 Neurons As Regulators Of the Hypothalamo-pituitary Gomentioning

confidence: 99%

Functional Implications of RFRP-3 in the Central Control of Daily and Seasonal Rhythms in Reproduction

et al. 2019

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Adaptation of reproductive activity to environmental changes is essential for breeding success and offspring survival. In mammals, the reproductive system displays regular cycles of activation and inactivation which are synchronized with seasonal and/or daily rhythms in environmental factors, notably light intensity and duration. Thus, most species adapt their breeding activity along the year to ensure that birth and weaning of the offspring occur at a time when resources are optimal. Additionally, female reproductive activity is highest at the beginning of the active phase during the period of full oocyte maturation, in order to improve breeding success. In reproductive physiology, it is therefore fundamental to delineate how geophysical signals are integrated in the hypothalamo-pituitary-gonadal axis, notably by the neurons expressing gonadotropin releasing hormone (GnRH). Several neurochemicals have been reported to regulate GnRH neuronal activity, but recently two hypothalamic neuropeptides belonging to the superfamily of (Arg)(Phe)-amide peptides, RFRP-3 and kisspeptin, have emerged as critical for the integration of environmental cues within the reproductive axis. The goal of this review is to survey the current understanding of the role played by RFRP-3 in the temporal regulation of reproduction, and consider how its effect might combine with that of kisspeptin to improve the synchronization of reproduction to environmental challenges.

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Section: Rfrp-3 Neurons As Regulators Of the Hypothalamo-pituitary Gomentioning

confidence: 99%

Functional Implications of RFRP-3 in the Central Control of Daily and Seasonal Rhythms in Reproduction

et al. 2019

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“…Consistent with this finding, GnIH/RFRP-3 and GPR147 were spatially and temporally expressed in other vertebrates’ ovaries [ 24 , 29 ]. Moreover, the dynamic expression of RFRP-3 was remarkably different in various species, with slightly high expression in the hypothalamus and pituitary of humans but abundantly expressed in pigs [ 23 , 36 ]. Our study confirmed that GnIH / RFRP-3 and its receptor GPR147 were mainly expressed in yak ovarian cells, and they might regulate the ovarian steroidogenesis function in an autocrine and/or paracrine manner.…”

Section: Discussionmentioning

confidence: 99%

RFRP-3 Influences Apoptosis and Steroidogenesis of Yak Cumulus Cells and Compromises Oocyte Meiotic Maturation and Subsequent Developmental Competence

Xiong

Pan

et al. 2023

IJMS

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RF amide-related peptide 3 (RFRP-3), a mammalian ortholog of gonadotropin-inhibitory hormone (GnIH), is identified to be a novel inhibitory endogenous neurohormonal peptide that regulates mammalian reproduction by binding with specific G protein-coupled receptors (GPRs) in various species. Herein, our objectives were to explore the biological functions of exogenous RFRP-3 on the apoptosis and steroidogenesis of yak cumulus cells (CCs) and the developmental potential of yak oocytes. The spatiotemporal expression pattern and localization of GnIH/RFRP-3 and its receptor GPR147 were determined in follicles and CCs. The effects of RFRP-3 on the proliferation and apoptosis of yak CCs were initially estimated by EdU assay and TUNEL staining. We confirmed that high-dose (10−6 mol/L) RFRP-3 suppressed viability and increased the apoptotic rates, implying that RFRP-3 could repress proliferation and induce apoptosis. Subsequently, the concentrations of E2 and P4 were significantly lower with 10−6 mol/L RFRP-3 treatment than that of the control counterparts, which indicated that the steroidogenesis of CCs was impaired after RFRP-3 treatment. Compared with the control group, 10−6 mol/L RFRP-3 treatment decreased the maturation of yak oocytes efficiently and subsequent developmental potential. We sought to explore the potential mechanism of RFRP-3-induced apoptosis and steroidogenesis, so we observed the levels of apoptotic regulatory factors and hormone synthesis-related factors in yak CCs after RFRP-3 treatment. Our results indicated that RFRP-3 dose-dependently elevated the expression of apoptosis markers (Caspase and Bax), whereas the expression levels of steroidogenesis-related factors (LHR, StAR, 3β-HSD) were downregulated in a dose-dependent manner. However, all these effects were moderated by cotreatment with inhibitory RF9 of GPR147. These results demonstrated that RFRP-3 adjusted the expression of apoptotic and steroidogenic regulatory factors to induce apoptosis of CCs, probably through binding with its receptor GPR147, as well as compromised oocyte maturation and developmental potential. This research revealed the expression profiles of GnIH/RFRP-3 and GPR147 in yak CCs and supported a conserved inhibitory action on oocyte developmental competence.

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“…Compelling evidence has documented a role of RFRP-3 in regulating GnRH and GHRH neuronal expression and function as well as secretion of gonadotrophin and steroid hormones and impacting the expression of Kisspeptin in mammals ( Johnson et al, 2007 ; Ducret et al, 2009 ; Kadokawa et al, 2009 ; Ancel et al, 2012 ; Li et al, 2013 ). The pig RFRP gene was found to be abundantly expressed in the nervous system (cerebellum, cerebrum, hypothalamus, and pituitary) and reproduction system (ovary, oviduct, uterus, and testis), and is thought to be a candidate gene for porcine reproductive traits ( Fang et al, 2014 ).…”

Section: Neuropeptide Modulators Of Gnrh Neuronal Activity Gnrh Secretion and Reproduction That Act Directly On Gnrh Neuronsmentioning

confidence: 99%

The neuroendocrine pathways and mechanisms for the control of the reproduction in female pigs

et al. 2021

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Within the hypothalamic-pituitary-gonad (HPG) axis, the major hierarchical component is gonadotropin-releasing hormone (GnRH) neurons, which directly or indirectly receive regulatory inputs from a wide array of regulatory signals and pathways, involving numerous circulating hormones, neuropeptides, and neurotransmitters, and which operate as a final output for the brain control of reproduction. In recent years, there has been an increasing interest in neuropeptides that have the potential to stimulate or inhibit GnRH in the hypothalamus of pigs. Among them, Kisspeptin is a key component in the precise regulation of GnRH neuron secretion activity. Besides, other neuropeptides, including neurokinin B (NKB), neuromedin B (NMB), neuromedin S (NMS), α-melanocyte-stimulating hormone (α-MSH), Phoenixin (PNX), show potential for having a stimulating effect on GnRH neurons. On the contrary, RFamide-related peptide-3 (RFRP-3), endogenous opioid peptides (EOP), neuropeptide Y (NPY), and Galanin (GAL) may play an inhibitory role in the regulation of porcine reproductive nerves and may directly or indirectly regulate GnRH neurons. By combining data from suitable model species and pigs, we aim to provide a comprehensive summary of our current understanding of the neuropeptides acting on GnRH neurons, with a particular focus on their central regulatory pathways and underlying molecular basis.

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Identification and characterization of RFRP gene in pigs and its association with reproductive traits

Cited by 10 publications

References 22 publications

Functional Implications of RFRP-3 in the Central Control of Daily and Seasonal Rhythms in Reproduction

Functional Implications of RFRP-3 in the Central Control of Daily and Seasonal Rhythms in Reproduction

RFRP-3 Influences Apoptosis and Steroidogenesis of Yak Cumulus Cells and Compromises Oocyte Meiotic Maturation and Subsequent Developmental Competence

The neuroendocrine pathways and mechanisms for the control of the reproduction in female pigs

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