Neuromedin S Regulates Steroidogenesis through Maintaining Mitochondrial Morphology and Function via NMUR2 in Goat Ovarian Granulosa Cells

Sun, Xuan; Cheng, Zhigang; Wang, Zhen; Zhang, Zhen; Yang, Fan; Liu, Zhipeng; Li, Kang; Zhang, Guomin

doi:10.3390/ijms232113402

Cited by 5 publications

(10 citation statements)

References 65 publications

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“…In our study, NMS participated in testosterone synthesis through up‐regulating the expression of STAR, CYP11A1, 3BHSD and CYP17A1, which is consistent with previous study in pig LCs 7 . Consistent with our previous observations, knockdown of NMUR2 inhibited the expression of STAR, CYP11A1 and 3BHSD in goat granulosa cells 13 . These data provide evidence that NMS participated in the synthesis and secretion of testosterone through regulating steroidogenic enzymes mainly via binding to NMUR2.…”

Section: Discussionsupporting

confidence: 93%

“…7 Consistent with our previous observations, knockdown of NMUR2 inhibited the expression of STAR, CYP11A1 and 3BHSD in goat granulosa cells. 13 These data provide evidence that NMS participated in the synthesis and secretion of testosterone through regulating steroidogenic enzymes mainly via binding to NMUR2.…”

Section: Discussionmentioning

confidence: 75%

“…Progesterone can act directly on granulosa cells through its receptor to affect cell proliferation, and in the adrenal gland cortex, estrogen deficiency can cause the impairment of cell proliferation. 11,12 In addition, NMS can affect mitochondrial morphology and function in granulosa cells, 13 and play an important role in the proliferation of splenic lymphocytes. 14 Although numerous studies are mentioned above, there is no clear evidence that NMS affects steroidogenesis and cell proliferation in goat LCs through regulating mitochondrial functions.…”

Section: Introductionmentioning

confidence: 99%

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Neuromedin S regulates steroidogenesis and proliferation in goat Leydig cells through modulating mitochondrial function

et al. 2023

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Neuromedin S (NMS) is a neuroregulatory substance and has many important roles in regulating physiological functions in animal cells, while their specific functions and mechanisms in Leydig cells (LCs) of the testis remain unclear.The current study aims to investigate the role and potential mechanisms of NMS and its receptors in regulating steroidogenesis and proliferation in goat LCs. We found that NMS and its receptors were mainly expressed in LCs of goat testes at different ages (1-day-old, 3-month-old, and 9-month-old), and the highest expressions detected at age three months. NMS addition significantly enhanced the testosterone secretion, STAR, CYP11A1, 3BHSD, and CYP17A1 expressions, cell proliferation, and PCNA expression in vitro cultured goat LCs. Mechanistically, NMS addition increased G1/S cell population, the expressions of CCND1, CDK4 and CDK6, the activities of SOD2 and CAT, and enhanced the mitochondrial fusion, the production of ATP, and mitochondrial membrane potential, while inhibited cellular ROS production, and maintained a low ubiquitination level of mitochondrial proteins. Notably, these effects of NMS addition on goat LCs were suppressed by co-treatment with NMUR2 knockdown. Therefore, these data suggest that activating NMUR2 with NMS enhances testosterone production and cell proliferation in goat LCs through modulating mitochondrial morphology, function, and autophagy. These findings may provide a novel view of the regulatory mechanisms involved in male sexual maturation.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

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Neuromedin S regulates steroidogenesis and proliferation in goat Leydig cells through modulating mitochondrial function

et al. 2023

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“…And NMS has been shown to enhance testosterone production and cell proliferation in goat Leydig cells by regulating mitochondrial morphology, function, and autophagy through the activation of NMUR2 (Sun et al, 2023). Another study by Sun et al (Sun et al, 2022) demonstrated that NMS may affect steroidogenesis in goat ovarian granulosa cells through the NMUR2/YAP1/PPARGC1A pathway. PIK3R6 is involved in various animal immune system pathways and related biological processes, including the B-cell receptor signaling pathway, AMPK signaling pathway, and Tcell differentiation regulation.…”

Section: Discussionmentioning

confidence: 98%

Population structure, runs of homozygosity analysis and construction of single nucleotide polymorphism fingerprinting database of Longnan goat population

Ma,

Li,

et al. 2023

Food and Energy Security

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The Longnan goat (LN) is a local breed discovered during the third census of China's livestock and poultry genetic resources. In order to thoroughly comprehend the population traits, this research examined a total of 70 animals from three different goat populations, namely the LN goat, Nanjiang Brown goat (NJ), and Boer goat (Boer). Specific‐Locus Amplified Fragment Sequencing was employed to analyze genetic diversity, population structure, and selective sweep patterns. Additionally, individual DNA fingerprints were generated to provide detailed genetic profiles for each subject. A total of 643,868 single nucleotide polymorphisms (SNPs) were detected, with a majority located in intergenic and intronic regions. Genetic diversity analysis uncovered lower diversity within the LN population compared to the other two populations. The analysis of population structure unveiled significant genetic distance between LN and both NJ and Boer populations, with distinct clustering patterns observed. Moreover, genetic differentiation coefficients (FST) of 0.1019 and 0.0854 were determined between LN and Boer, as well as LN and NJ, respectively, indicating substantial genetic differentiation. Selective sweep analysis, combining FST and π ratio, identified several genes associated with growth and development, reproduction, hair color, and immunity that may serve as valuable candidates for marker‐assisted breeding. Furthermore, identification of 47,541 runs of homozygosity (ROHs) revealed non‐uniform distribution across chromosomes, with the highest frequency on chromosome 1 and the lowest on chromosome 27. Correlations between different inbreeding coefficients varied, with the highest observed between FHOM and FGRM, and the lowest between FROH >1.5Mb and FROH <500kb. A total of 46 candidate genes were annotated within high‐frequency ROH islands, primarily associated with biological processes such as reproduction, growth and development, and immunity. Finally, a DNA fingerprint, consisting of 371 highly polymorphic SNPs, was generated and presented in the form of a two‐dimensional code for convenient access. Based on the population structure analysis, LN goats have been found to have a distant genetic distance and a higher degree of differentiation from both the Boer and NJ populations. Evaluation of genetic diversity parameters and ROH analysis indicates that the LN population exhibits lower genetic diversity and shows signs of inbreeding. Our findings offer theoretical support for the identification of genetic resources within this population.

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“…Severe defects in luteinization, steroidogenesis, and disordered mitochondrial morphology and function in response to gonadotropins were detected in granulosa cells with MIGA1/2 knockout (Liu et al, 2017). In goat ovarian granulosa cells, upregulation of OPA1, MFN1 , and MFN2 enhanced the fusion of mitochondria, mitochondrial membrane potential, the activity of respiratory chain enzymes, and the production of steroid and ATP (Sun et al, 2022). In the present study, we found that both mRNA and protein levels of MFN2 in granulosa cells of hierarchical follicles were significantly higher than those in SYFG, and expression levels of MFN2 in granulosa cells upregulated significantly around the time of follicle selection.…”

Section: Discussionmentioning

confidence: 99%

MFN2 regulates progesterone biosynthesis and proliferation of granulosa cells during follicle selection in hens

Hou,

Hu,

et al. 2023

Journal Cellular Physiology

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Follicle selection in hens refers to a biological process that only one small yellow follicle (SYF) is selected daily or near‐daily for following hierarchical development (from F5/F6 to F1) until ovulation. MFN2 is a kind of GTPases located on the mitochondrial outer membrane, which plays a crucial role in mitochondrial fusion. This study aimed to elucidate the role of MFN2 in proliferation and progesterone biosynthesis of granulosa cells (GCs) during follicle selection in hens. The results showed that GCs began to produce progesterone (P4) after follicle selection, accompanied with changes from multi‐layer with flat cells to single layer with cubic cells. MFN2 was detected in GCs of follicles from SYF to F1. After follicle selection, the expression level of MFN2 in GCs upregulated significantly, accompanied with increases in P4 biosynthesis, ATP production, mitochondrial DNA (mtDNA) copy numbers of granulosa cells. FSH (80 ng/mL) facilitated the effects of P4 biosynthesis and secretion, ATP production, mtDNA copy numbers, cell proliferation and the MFN2 transcription of granulosa cells from F5 (F5G) in vitro. However, FSH treatment did not promote P4 secretion in granulosa cells from SYF (SYFG) in vitro. Meanwhile, we observed that change fold of MFN2 transcription, ATP production, mtDNA copy numbers and cell proliferation rate in F5G after treatment with FSH were greater than those in SYFG. Furthermore, expression levels of MFN2 protein and messenger RNA in F5G were significantly higher than those in SYFG after treatment with FSH. P4 biosynthesis, ATP production, mtDNA copy numbers as well as cell proliferation reduced significantly in F5G with MFN2 knockdown. Oppositely, P4 biosynthesis, ATP production, mtDNA copy numbers and cell proliferation increased significantly in SYFG after the overexpression of MFN2. Our results suggest that the upregulation of MFN2 may be involved in the initiation of P4 biosynthesis, and promotion of GCs proliferation during follicle selection.

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Neuromedin S Regulates Steroidogenesis through Maintaining Mitochondrial Morphology and Function via NMUR2 in Goat Ovarian Granulosa Cells

Cited by 5 publications

References 65 publications

Neuromedin S regulates steroidogenesis and proliferation in goat Leydig cells through modulating mitochondrial function

Neuromedin S regulates steroidogenesis and proliferation in goat Leydig cells through modulating mitochondrial function

Population structure, runs of homozygosity analysis and construction of single nucleotide polymorphism fingerprinting database of Longnan goat population

MFN2 regulates progesterone biosynthesis and proliferation of granulosa cells during follicle selection in hens

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