PPP2R2A promotes testosterone secretion in Hu sheep Leydig cells via activation of the AKT/mTOR signaling pathway

in Journal of Molecular Endocrinology
Authors:
Xiaodan LiCollege of Animal Science and Technology, Nanjing Agricultural University, No. 1 Weigang, Nanjing, 210095, China

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Xiaolei YaoCollege of Animal Science and Technology, Nanjing Agricultural University, No. 1 Weigang, Nanjing, 210095, China

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Yongjin BaoCollege of Animal Science and Technology, Nanjing Agricultural University, No. 1 Weigang, Nanjing, 210095, China

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Kaiping DengCollege of Animal Science and Technology, Nanjing Agricultural University, No. 1 Weigang, Nanjing, 210095, China

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Mingtian DengCollege of Animal Science and Technology, Nanjing Agricultural University, No. 1 Weigang, Nanjing, 210095, China

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Fan YangCollege of Animal Science and Technology, Nanjing Agricultural University, No. 1 Weigang, Nanjing, 210095, China

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Xuan SunCollege of Animal Science and Technology, Nanjing Agricultural University, No. 1 Weigang, Nanjing, 210095, China

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Peihua YouCollege of Animal Science and Technology, Nanjing Agricultural University, No. 1 Weigang, Nanjing, 210095, China

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Qingxian CaiCollege of Animal Science and Technology, Nanjing Agricultural University, No. 1 Weigang, Nanjing, 210095, China

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Feng WangCollege of Animal Science and Technology, Nanjing Agricultural University, No. 1 Weigang, Nanjing, 210095, China

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Correspondence should be addressed to F Wang: caeet@njau.edu.cn
DOI:
https://doi.org/10.1530/JME-22-0130
Volume/Issue:
Volume 70: Issue 4
Article Type:
Research Article
Article ID:
e220130
Online Publication Date:
17 Apr 2023
Copyright:
© Society for Endocrinology 2023
Restricted access

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The serine-threonine protein phosphatase 2A (PP2A) is a heterotrimeric enzyme complex that plays a vital role in regulating male reproductive activities. However, as an essential member of the PP2A family, the physiological functions of PP2A regulatory subunit B55α (PPP2R2A) in testis remain inconclusive. Hu sheep are noted for their reproductive precocity and fertility, and are ideal models for the study of male reproductive physiology. Here, we analyzed the expression patterns of PPP2R2A in the male Hu sheep reproductive tract at different developmental stages and further investigated its role in testosterone secretion and its underlying mechanisms. In this study, we found that there were temporal and spatial differences in PPP2R2A protein expression in the testis and epididymis, especially the expression abundance in the testis at 8 months old (8M) was higher than that at 3 months old (3M). Interestingly, we observed that PPP2R2A interference reduced the testosterone levels in the cell culture medium, which is accompanied by a reduction in Leydig cell proliferation and an elevation in Leydig cell apoptosis. The level of reactive oxygen species in cells increased significantly, while the mitochondrial membrane potential (ΔΨm) decreased significantly after PPP2R2A deletion. Meanwhile, the mitochondrial mitotic protein DNM1L was significantly upregulated, while the mitochondrial fusion proteins MFN1/2 and OPA1 were significantly downregulated after PPP2R2A interference. Furthermore, PPP2R2A interference suppressed the AKT/mTOR signaling pathway. Taken together, our data indicated that PPP2R2A enhanced testosterone secretion, promoted cell proliferation, and inhibited cell apoptosis in vitro, all of which were associated with the AKT/mTOR signaling pathway.

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Print ISSN:
0952-5041
Online ISSN:
1479-6813
Copyright:
© Society for Endocrinology 2023
Article ID:
e220130
Article Type:
Research Article
Received Date:
16 Feb 2023
Accepted Date:
24 Feb 2023
Print Publication Date:
01 May 2023
Online Publication Date:
17 Apr 2023
Keywords:
PPP2R2A; Leydig cells; testosterone secretion; AKT/mTOR signaling pathway

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