Hyperhomocysteinemia in polycystic ovary syndrome: decreased betaine-homocysteine methyltransferase and cystathionine β-synthase-mediated homocysteine metabolism

• Published in: Reproductive biomedicine online 2018-08, Vol.37 (2), p.234-241
• Main Authors: Li, Da, Liu, Hong-Xiang, Fang, Yuan-Yuan, Huo, Jia-Ning, Wu, Qi-Jun, Wang, Tian-Ren, Zhou, Yi-Ming, Wang, Xiu-Xia, Ma, Xiao-Xin
• Format: Article
• Language: English
• Subjects: Bhmt; Cbs; Homocysteine; Metabolism; Mtr; Polycystic ovary syndrome
• ISSN: 1472-6483; 1472-6491
• DOI: 10.1016/j.rbmo.2018.05.008

What are the metabolic characteristics of homocysteine in polycystic ovary syndrome (PCOS)? Homocysteine concentrations were determined in serum samples from non-obese and obese control subjects and PCOS patients. Homocysteine metabolism was studied in a rat model of PCOS established using dehydroepiandrosterone (DHEA) or DHEA in combination with a high-fat diet (HFD). It was shown that (i) serum homocysteine concentrations were greater in PCOS patients than in control subjects in the obese group (P < 0.05) and serum homocysteine concentrations were significantly higher in the obese group than in the non-obese group, regardless of PCOS status (both P < 0.05); (ii) serum homocysteine concentrations were significantly increased in DHEA + HFD-induced rats compared with controls (P < 0.05); (iii) when compared with the control group, mRNA concentrations of homocysteine metabolic enzymes Bhmt and Cbs were significantly reduced in the liver tissues of DHEA + HFD-induced rats (both P < 0.0001); (iv) when compared with the control group, there was a significant decrease in the methylation concentrations of the Cbs (P < 0.05) and Bhmt (P < 0.05 and P < 0.0001) promoter in the DHEA + HFD group. The methylation patterns, together with previous data, indicate that hypomethylated promoter-mediated transcriptional activation of Bhmt and Cbs might be a defence mechanism against PCOS-related hyperhomocysteinemia. These findings indicate that decreased liver Bhmt and Cbs-mediated homocysteine metabolism might have a role in hyperhomocysteinemia in PCOS and provides further evidence for a potential role of decreased liver function in PCOS.