Role of CPXM1 in Impaired Glucose Metabolism and Ovarian Dysfunction in Polycystic Ovary Syndrome

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.

Keywords: Carboxypeptidase X, M14 family member 1 (CPXM1); Glucose metabolism; Inflammation; Ovarian dysfunction; Polycystic ovary syndrome (PCOS).