2. Academic Validation
  3. Reprogramming of DNA methylation patterns mediates perfluorooctane sulfonate-induced fetal cardiac dysplasia

Reprogramming of DNA methylation patterns mediates perfluorooctane sulfonate-induced fetal cardiac dysplasia

  • Sci Total Environ. 2024 Apr 1:919:170905. doi: 10.1016/j.scitotenv.2024.170905.
Min Qiu 1,  Jing Chen 2,  Mingqin Liu 3,  Yan Shi 1,  Zhiqiang Nie 4,  Guanghui Dong 5,  Xiaohong Li 2,  Jimei Chen 1,  Yanqiu Ou 6,  Jian Zhuang 7
Affiliations

Affiliations

  • 1 Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
  • 2 Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
  • 3 Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China; Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
  • 4 Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
  • 5 Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
  • 6 Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China; Department of Epidemiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China. Electronic address: ouyanqiu@gdph.org.cn.
  • 7 Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China. Electronic address: zhuanjian@gdph.org.cn.
PMID: 38350568 DOI: 10.1016/j.scitotenv.2024.170905
Abstract

Prenatal exposure to perfluorooctane sulfonate (PFOS) is associated with adverse health effects, including congenital heart disease, yet the underlying mechanisms remain elusive. Herein, we aimed to evaluate the embryotoxicity of PFOS using C57BL/6 J mice to characterize fetal heart defects after PFOS exposure, with the induction of human embryonic stem cells (hESC) into cardiomyocytes (CMs) as a model of early-stage heart development. We also performed DNA methylation analysis to clarify potential underlying mechanisms and identify targets of PFOS. Our results revealed that PFOS caused septal defects and excessive ventricular trabeculation cardiomyopathy at 5 mg/kg/day in embryonic mice and inhibited the proliferation and pluripotency of ESCs at concentrations >20 μM. Moreover, it decreased the beating rate and the population of CMs during cardiac differentiation. Decreases were observed in the abundances of NPPA+ trabecular and HEY2+ compact CMs. Additionally, DNA methyl transferases and ten-eleven translocation (TET) dioxygenases were regulated dynamically by PFOS, with TETs inhibitor treatment inducing significant decreases similar as PFOS. 850 K DNA methylation analysis combined with expression analysis revealed several potential targets of PFOS, including SORBS2, FHOD1, SLIT2, SLIT3, ADCY9, and HDAC9. In conclusion, PFOS may reprogram DNA methylation, especially demethylation, to induce cardiac toxicity, causing ventricular defects in vivo and abnormal cardiac differentiation in vitro.

Keywords

Cardiac differentiation; Cardiomyocytes; Congenital heart defect; DNA methylation; Perfluorooctane sulfonate; TET dioxygenases.

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