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

Reprod. Biomed. Online. 2018 Aug;37(2):234-241. Epub 2018 May 22
Da Li 1 , Hong-Xiang Liu 2 , Yuan-Yuan Fang 1 , Jia-Ning Huo 2 , Qi-Jun Wu 3 , Tian-Ren Wang 4 , Yi-Ming Zhou 5 , Xiu-Xia Wang 6 , Xiao-Xin Ma 7
Da Li 1 , Hong-Xiang Liu 2 , Yuan-Yuan Fang 1 , Jia-Ning Huo 2 , Qi-Jun Wu 3 , Tian-Ren Wang 4 , Yi-Ming Zhou 5 , Xiu-Xia Wang 6 , Xiao-Xin Ma 7
+ et al

[No authors listed]

Author information
  • 1 Centre of Reproductive Medicine, ShengJing Hospital of China Medical University, Shenyang 110004, China.
  • 2 Department of Obstetrics and Gynecology, ShengJing Hospital of China Medical University, Shenyang 110004, China.
  • 3 Department of Clinical Epidemiology, ShengJing Hospital of China Medical University, Shenyang 110004, China.
  • 4 Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT 06520, USA.
  • 5 Department of Medicine, Brigham and Women's Hospital, Harvard Institutes of Medicine, Harvard Medical School, Boston, MA 02115, USA.
  • 6 Centre of Reproductive Medicine, ShengJing Hospital of China Medical University, Shenyang 110004, China. Electronic address: wangxxsj@sina.cn.
  • 7 Department of Obstetrics and Gynecology, ShengJing Hospital of China Medical University, Shenyang 110004, China. Electronic address: maxiaoxin666@aliyun.com.

摘要


RESEARCH QUESTION:What are the metabolic characteristics of homocysteine in polycystic ovary syndrome (PCOS)? DESIGN: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). RESULTS: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. CONCLUSIONS: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.

KEYWORDS: Bhmt, Cbs, Homocysteine, Metabolism, Mtr, Polycystic ovary syndrome