Abstract
Polycystic ovary syndrome (PCOS), a common female endocrinopathy associated with both reproductive and metabolic disorders, has an unclear etiology and unsatisfactory management methods. Carboxypeptidase X, M14 family member 1 (CPXM1) is a protein involved in follicular atresia, insulin production, and adipose tissue production, though its role in PCOS is not fully understood. We used a 60% high-fat diet (HFD) plus dehydroepiandrosterone (DHEA)-induced PCOS mouse model to determine the role of CPXM1 in abnormal glucose metabolism and ovarian dysfunction in PCOS. We found that serum CPXM1 concentrations were higher in PCOS mice and positively correlated with increased levels of serum testosterone and insulin. In both ovarian and adipose tissues of PCOS mice, CPXM1 mRNA and protein levels were significantly increased but GLUT4 levels were significantly decreased. Immunohistochemistry (IHC) staining of the ovary showed increased CPXM1 expression in PCOS. In addition, the protein expression of phosphorylated protein kinase B (p-Akt) was also significantly decreased in PCOS mice. Furthermore, mRNA levels of inflammatory markers such as TNF-α, IL-6, IFN-α, and IFN-γ were increased in ovarian and adipose tissues of PCOS mice. However, IRS-1, IRS-2, and INSR levels were significantly decreased. Our results indicated for the first time that abnormally high expression of CPXM1, increased adiposity, impaired glucose tolerance, and chronic low-grade inflammation may act together in a vicious cycle in the pathophysiology of PCOS. Our research suggests the possibility of CPXM1 as a potential therapeutic target for the treatment of PCOS.
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Change history
07 July 2022
A Correction to this paper has been published: https://doi.org/10.1007/s43032-022-01021-x
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Acknowledgements
We thank Jun-Pu Yang and Antonia Adwoa Otoo for the help provided in the processing of tissues and revising the manuscript.
Funding
This study was supported by grants from the National Natural Science Foundation of China (No. 82171624), the Chongqing Natural Science Foundation (No. cstc2020jcyj-msxmX0294), Science and Technology Project of Chongqing Yuzhong District (No. 20200103), and Scientific Research and Innovation Experiment Project of Chongqing Medical University (SRIEP202106; SRIEP202002).
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Sadaf Pervaz: experiment performance, formal analysis, and preparation of the manuscript. Mei-Jiao Wang: study design, methodology, resources, supervision, review, and editing. Amin Ullah: investigation and formal analysis. Enoch Appiah Adu-Gyamfi: formal analysis, review, and editing. Lamptey Jones: formal analysis, review, and editing. Sanjay Kumar Sah: review and editing. Ying-Xiong Wang: fund acquisition, conceptualization, supervision.
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The study was approved by the Animal Ethics Committee of Chongqing Medical University on 6 June 2012 (certification no: SCXK [YU] 20210607).
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This article was update to correct Enoch Appiah Adu-Gyamfi's name.
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Fig. S1 Vaginal smear examination. a Proestrus stage of mice (round, nucleated epithelial cells). b Estrus (cornified squamous epithelial cells). c Metestrus (round, nucleated epithelial cells, cornified squamous epithelial cells, and leukocytes). d Diestrus (predominance of leukocytes). Black arrows represent the proestrus stage; red arrows show estrus; black, blue, and red arrows show metestrus; blue arrows show diestrus. (PNG 2842 kb)
Supplementary file2
Fig. S2 Correlation of the serum levels of CPXM1 with progesterone, LH, and serum FSH. a-c Correlation of the serum levels of CPXM1 with (a) serum progesterone, (b) serum LH, (c) serum FSH. p = 0.1794, p = 0.1470, p = 0.2426. n = 10 per group. (PNG 205 kb)
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Pervaz, S., Ullah, A., Adu-Gyamfi, E.A. et al. Role of CPXM1 in Impaired Glucose Metabolism and Ovarian Dysfunction in Polycystic Ovary Syndrome. Reprod. Sci. 30, 526–543 (2023). https://doi.org/10.1007/s43032-022-00987-y
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DOI: https://doi.org/10.1007/s43032-022-00987-y