Gonadotropin-inhibiting hormone promotes apoptosis of bovine ovary granulosa cells

Xu, Longhe; Xu, Gaoqing; Li, Zhiqiang; Liu, Hongyu; Ma, Xin; Yang, Lei; Zhang, Pengju; Zhao, Jing; Wang, Jun; Lu, Wenfa

doi:10.1016/j.lfs.2021.119063

Cited by 7 publications

(7 citation statements)

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“…GnIH, a t12-amino acid residue neuropeptide hormone, is concerned with numerous behavioral and physiological functions in animal reproduction [ 10 ], including the suppression of steroidogenesis and follicular growth in female ovarian tissues [ 26 , 30 , 31 ]. The reproductive performance of mammals is primarily affected by the number of mature follicles that can develop to ovulation.…”

Section: Discussionmentioning

confidence: 99%

“…In other words, GnIH/RFRP-3 and GPR147 may be responsible for the fate of a follicle to grow or develop atresia. Additionally, a dramatic upregulation of GnIH/RFRP-3 during diestrus is likely involved in follicular development and selection, as well as corpus luteum activity [ 31 ]. The present study also revealed that GnIH/RFRP-3 and GPR147 were dynamically expressed in the various stages of follicles and corpus luteum in yak ovaries.…”

Section: Discussionmentioning

confidence: 99%

“…In agreement with our findings, RFRP-3 also conspicuously downregulated the transcription of proliferation-related factors in porcine GCs in vitro [ 38 ]. RFRP-3 drastically reduced the expression of CDC42, PCNA, and CCND1 in mRNA levels to inhibit bovine GC proliferation [ 31 ]. Therefore, RFRP-3 has a negative effect on the proliferation of yak CCs, although we cannot rule out the possibility of an underlying mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…Recent reports indicated that GnIH/RFRP-3 mediates autophagy and apoptosis of epididymal cells in rats and suppresses GC proliferation in pigs. Similarly, in cattle and porcine, GnIH/RFRP-3 inhibits GC proliferation, damages mitochondrial function, and promotes GC apoptosis by notably decreasing the p38 phosphorylation level [ 31 , 37 , 38 ]. In male mammals, GnIH/RFRP-3 induces testicular and epididymal apoptosis via mediating p53, Bax, and Capase-3 [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

“…A recent study on mice indicated that ovarian activity and follicular growth are suppressed after treatment with RFRP-3 [ 26 ]. Immunohistochemistry (IHC) found that RFRP-3 and its receptors are primarily expressed in GCs and membrane cells of bird and pig ovarian follicles [ 25 , 30 ], and GnIH/RFRP-3 plays a crucial regulatory effect in the ovaries via combining with its receptors, such as adjusting apoptosis, proliferation, and steroidogenesis [ 31 ]. However, as the main domestic animal in the Qinghai-Tibet Plateau region and nearby areas, whether the low reproductive efficiency of female yak is related to GnIH/RFRP-3 remains unclear and needs further investigation, as well as to evaluate whether RFRP-3 exerts conserved function across various species.…”

Section: Introductionmentioning

confidence: 99%

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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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