High Maternal Serum Estradiol Levels Induce Dyslipidemia in Human Newborns via a Hepatic HMGCR Estrogen Response Element.

Abstract

UNLABELLED:

While the intrauterine environment is essential for the health of offspring, the impact of high maternal serum estradiol (E2) on lipid metabolism in offspring and the mechanisms are unknown. We found that ovarian stimulation (OS) could result in high E2 levels in women throughout pregnancy. Strikingly, their newborns showed elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels that were positively related with E2 in newborns. In vitro, E2 dose-dependently stimulated TC and LDL-C secretion, and increased expression of the cholesterol synthesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) in HepG2 cells and mouse fetal hepatocytes. In vivo, high maternal E2 was detected and fetal livers also showed significantly higher HMGCR expression in an OS mouse model. Notably, an estrogen response element (ERE) was identified in the HMGCR promoter, indicating that high maternal serum E2 could up-regulate HMGCR expression in fetal hepatocytes via an ERE that in turn induces elevated levels of TC and LDL-C in offspring.

CONCLUSION:

OS can induce a high maternal E2 environment, which up-regulates HMGCR expression in fetal hepatocytes via an ERE in the promoter, and induces elevated levels of TC and LDL-C in newborns that may be related to increased risk of metabolic disease in adulthood.

• Authors: Ye Meng, Ping-Ping Lv, Guo-Lian Ding, Tian-Tian Yu, Ye Liu, Yan Shen, Xiao-Ling Hu, Xian-Hua Lin, Shen Tian, Min Lv, Yang Song, Meng-Xi Guo, Zhang-Hong Ke, Hong Xu, Jian-Zhong Sheng, Feng-Tao Shi, He-Feng Huang
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 10086 (May 11 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 25961186 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cholesterol, LDL
• Estradiol
• HMGCR protein, human
• Hydroxymethylglutaryl CoA Reductases

Topics

• Animals
• Cholesterol, LDL (blood)
• Disease Models, Animal
• Dyslipidemias (blood, etiology)
• Estradiol (blood)
• Female
• Hep G2 Cells
• Humans
• Hydroxymethylglutaryl CoA Reductases (metabolism)
• Infant, Newborn
• Infant, Newborn, Diseases (blood, etiology)
• Male
• Mice
• Mice, Inbred ICR
• Pregnancy
• Pregnancy Complications (blood)