BMP15 regulates FSHR through TGF-β receptor II and SMAD4 signaling in prepubertal ovary of Rongchang pigs

Ma, Xiuli; Yi, Huashan

doi:10.1016/j.rvsc.2021.12.013

Cited by 7 publications

(4 citation statements)

References 31 publications

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“…However, our study found an inverse relationship between serum estrogen concentrations in Wanyue Black gilts and the expression level of BMP15 in ovaries. This discrepancy may be attributed to the involvement of BMP15 in the intricate BMP15/TGF-β/SMAD signaling pathway, which plays a role in the regulation of steroid hormone production [ 40 ]. This study identified differentially expressed genes, including FOS, CEBPB, JUNB, FOSL1, BMP15, CYP11A1, SOCS3, ZP3, and HSD3B1, in Wanyue Black and Yorkshire gilt ovaries.…”

Section: Discussionmentioning

confidence: 99%

Comparative Analysis of the Ovary Transcriptome among Wanyue Black and Yorkshire Gilts Using RNA-Seq

Zhang,

Chen,

Liu

et al. 2024

Veterinary Sciences

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Pubertal genetic variations between the indigenous Chinese Wanyue Black pig breed and the imported Yorkshire breed significantly impact their reproductive capacity. In order to identify the differentially expressed genes, gene networks, and metabolic pathways in ovary transcriptome of gilts, the serum hormone levels were analyzed by ELISA, and RNA-seq was performed to analyze ovarian genes. Our results reveal higher estradiol (E2) levels in Wanyue black gilts compared to Yorkshire gilts, while Yorkshire gilts exhibit elevated progesterone (P4) and GnRH levels. We identified a total of 154 differentially expressed genes (DEGs), with 87 up-regulated and 67 down-regulated genes in the Wanyue black gilts ovaries compared to the Yorkshire gilts. GO enrichment analysis unveiled the participation of DEGs in processes such as “Reproduction”, “Reproductive system development”, and “Ovarian follicle development”. Moreover, KEGG enrichment analysis revealed the involvement of DEGs in multiple signaling pathways associated with hormone biosynthesis and puberty, encompassing “Steroid hormone biosynthesis”, “Estrogen signaling pathway”, and “Prolactin signaling pathway”. The subsequent bioinformatics analysis identified nine functional genes that potentially contribute to the disparity in ovaries between Wanyue black gilts and Yorkshire gilts. This study offers significant insights into the endocrine and genetic aspects of pubertal development in gilts.

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Section: Discussionmentioning

confidence: 99%

Comparative Analysis of the Ovary Transcriptome among Wanyue Black and Yorkshire Gilts Using RNA-Seq

Zhang,

Chen,

Liu

et al. 2024

Veterinary Sciences

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“…SMAD4 is a key regulatory factor in the production of FSH [ 32 , 33 ]. Bone morphogenetic protein 15 (BMP15) regulates FSH receptor (FSHR) through TGF-β receptor II and SMAD4 signaling in porcine GCs to regulate follicular development [ 34 , 35 ]. Knockdown of SMAD4 significantly inhibited FSH-induced porcine GCs proliferation and estradiol production [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

miR-6881-3p contributes to diminished ovarian reserve by regulating granulosa cell apoptosis by targeting SMAD4

Ju,

Zhao,

et al. 2024

Reprod Biol Endocrinol

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Background In our previous investigation, we revealed a significant increase in the expression of microRNA-6881-3p (miR-6881-3p) in follicular fluid granulosa cells (GCs) from women with diminished ovarian reserve (DOR) compared to those with normal ovarian reserve (NOR). However, the role of miR-6881-3p in the development of DOR remains poorly understood. Objective This study aimed to elucidate the involvement of miR-6881-3p in the regulation of granulosa cells (GCs) function and the pathogenesis of DOR. Materials and methods Initially, we assessed the expression levels of miR-6881-3p in GCs obtained from human follicular fluid in both NOR and DOR cases and explored the correlation between miR-6881-3p expression and clinical outcomes in assisted reproduction technology (ART). Bioinformatic predictions and dual-luciferase reporter assays were employed to identify the target gene of miR-6881-3p. Manipulation of miR-6881-3p expression was achieved through the transfection of KGN cells with miR-6881-3p mimics, inhibitor, and miRNA negative control (NC). Following transfection, we assessed granulosa cell apoptosis and cell cycle progression via flow cytometry and quantified target gene expression through quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) analysis. Finally, we examined the correlation between target gene expression levels in GCs from NOR and DOR patients and their association with ART outcomes. Results Our findings revealed elevated miR-6881-3p levels in GCs from DOR patients, which negatively correlated with ovarian reserve function and ART outcomes. We identified a direct binding interaction between miR-6881-3p and the 3’-untranslated region of the SMAD4. Transfection with miR-6881-3p mimics induced apoptosis in KGN cell. Furthermore, miR-6881-3p expression negatively correlated with both mRNA and protein levels of the SMAD4. The mRNA and protein levels of SMAD4 were notably reduced in GCs from DOR patients, and SMAD4 mRNA expression positively correlated with ART outcomes. In addition, the mRNA levels of FSHR, CYP11A1 were notably reduced after transfection with miR-6881-3p mimics in KGN cell, while LHCGR notably increased. The mRNA and protein levels of FSHR, CYP11A1 were notably reduced in GCs from DOR patients, while LHCGR notably increased. Conclusion This study underscores the role of miR-6881-3p in directly targeting SMAD4 mRNA, subsequently diminishing granulosa cell viability and promoting apoptosis, and may affect steroid hormone regulation and gonadotropin signal reception in GCs. These findings contribute to our understanding of the pathogenesis of DOR.

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“…Rongchang pig is not only one of the eight excellent pig breeds in the world, but also one of the three excellent local pig breeds, which has been listed as a national class I protected breed resource in China [ 1 ]. As a typical fatty pig breed in southwest China, it has been reared for more than four decades and is mainly produced in Rongchang District of Chongqing.…”

Section: Introductionmentioning

confidence: 99%

“…Compared to large pigs, miniature pigs can reach sexual maturity earlier, while Rongchang pigs are smaller than three-breed crossbred sows, but larger than experimental miniature pigs. They have an earlier puberty with an average age of 106.1±18.7 days and an average weight of 26±10.2 kg, making them an ideal pig breed for pure line breeding and establishing specific pathogen free (SPF) populations [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

Characterization analysis of Rongchang pig population based on the Zhongxin-1 Porcine Breeding Array PLUS

Dong¹,

Ge²,

Sun³

2023

Anim Biosci

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Objective: To carry out a comprehensive production planning of the existing Rongchang pig population from both environmental and genetic aspects, and to establish a closed population with stable genetic diversity and strict pathogen control, it is necessary to fully understand the genetic background of the population.Methods: We genotyped 54 specific pathogen free (SPF) Rongchang pigs using the Zhongxin-1 Porcine Breeding Array PLUS, calculated their genetic diversity parameters and constructed their families. In addition, we also counted the runs of homozygosity (ROH) of each individual and calculated the value of inbreeding coefficient based on ROH for each individual.Results: Firstly, the results of genetic diversity analysis showed that the effective population size (Ne) of this population was 3.2, proportion of polymorphic markers (PN) was 0.515, desired heterozygosity (He) and observed heterozygosity (Ho) were 0.315 and 0.335. Ho was higher than He, indicating that the heterozygosity of all the selected loci was high. Secondly, combining the results of genomic relatedness analysis and cluster analysis, it was found that the existing Rongchang pig population could be divided into four families. Finally, we also counted the ROH of each individual and calculated the inbreeding coefficient value accordingly, whose mean value was 0.09.Conclusion: Due to the limitation of population size and other factors, the genetic diversity of this Rongchang pig population is low. The results of this study can provide basic data to support the development of Rongchang pig breeding program, the establishment of SPF Rongchang pig closed herd and its experimental utilization.

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BMP15 regulates FSHR through TGF-β receptor II and SMAD4 signaling in prepubertal ovary of Rongchang pigs

Cited by 7 publications

References 31 publications

Comparative Analysis of the Ovary Transcriptome among Wanyue Black and Yorkshire Gilts Using RNA-Seq

Comparative Analysis of the Ovary Transcriptome among Wanyue Black and Yorkshire Gilts Using RNA-Seq

miR-6881-3p contributes to diminished ovarian reserve by regulating granulosa cell apoptosis by targeting SMAD4

Characterization analysis of Rongchang pig population based on the Zhongxin-1 Porcine Breeding Array PLUS

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