2. Academic Validation
  3. EHDPP impairs intestinal microbiota homeostasis and induces placental injury through choline mediated gut-placenta axis

EHDPP impairs intestinal microbiota homeostasis and induces placental injury through choline mediated gut-placenta axis

  • J Hazard Mater. 2025 Feb 19:489:137573. doi: 10.1016/j.jhazmat.2025.137573.
Ting Du 1,  Saifei Lei 2,  Zhengyao Huang 1,  Xin Liu 3,  Zhou Jiang 4,  Minlan Lu 5,  Yiyang Zhou 5,  Jiali Yuan 1,  Weiyi Song 1,  Hao Gu 6,  Jing Li 7
Affiliations

Affiliations

  • 1 Key Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, 209 Tong-Shan Road, Xuzhou, Jiangsu 221002, China.
  • 2 School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.
  • 3 School of Medical Information and Engineering, Xuzhou Medical University, China.
  • 4 Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China.
  • 5 School of Life Sciences, Xuzhou Medical University, China.
  • 6 Department of Central Laboratory, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an 223300, China. Electronic address: hayygh@njmu.edu.cn.
  • 7 Key Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, 209 Tong-Shan Road, Xuzhou, Jiangsu 221002, China. Electronic address: 100002008046@xzhmu.edu.cn.
PMID: 40007358 DOI: 10.1016/j.jhazmat.2025.137573
Abstract

2-Ethylhexyl-diphenyl phosphate (EHDPP) is an organophosphate ester (OPE) with roles of flame retardant and plasticizer. It is widely used in various applications, detected in environmental matrices and human body, threatening ecological environment and human health. Some OPEs have been reported to disturb the gut microbiota, the gut microbiota mediates placental function. Our previous study showed EHDPP causes placental toxicity and fetal weight loss, it is unknown that whether EHDPP affects fetal development through the gut-placenta axis and whether it is feasible to fight against EHDPP induced placental toxicity through the gut-placenta axis. Our study investigates and indicates that EHDPP disrupts normal gut function by disturbing the gut microbiota homeostasis and compromising the intestinal barrier integrity. The disruption of EHDPP leads to reduced choline transporter expression of the solute carrier family 44A2 (SLC44A2), impaired choline absorption and distribution in placenta. Gut microbiota depletion increases the choline level in placenta. Both gut microbiota depletion and choline supplementation alleviate the EHDPP induced fetal weight loss by increasing the expression and activation of LXRα. In addition, a mendelian randomization study indicates that choline transporter SLC44A2 expression reduction significantly increased the risk of low birth weight in human. In summary, EHDPP exposure exacerbates placental and fetal damage through attenuating the beneficial function of choline mediated gut-placental axis. Direct choline supplementation or indirect choline level upregulation by gut microbiota depletion are therapeutic strategies for EHDPP induced placental injury.

Keywords

2-ethylhexyl-diphenyl phosphate; Choline; Fetal weight loss; Gut microbiota; Pregnant exposure.

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