Environmental chemicals and adverse pregnancy outcomes: Placenta as a target and possible driver of pre- and postnatal effects

Abstract

Human placenta is key to fetal growth and development as it controls maternal-to-fetal exchanges of endogenous and exogenous substances. Despite numerous studies have investigated prenatal exposure to environmental chemicals and associated effects on adverse pregnancy outcomes (APOs), the role of placenta as a direct target of environmental chemicals and possible driver of pre- and postnatal effects has been largely overlooked. In the present work, we demonstrated that more than 330 environmental chemicals have been reported in human placenta, among which 260 chemicals exhibited an estimated median concentration from 3 pg/g to 5150 ng/g lipid weight in human placenta. We also discussed the main mechanisms through which environmental chemicals interfere with placental development and functions and cause a variety of possible APOs. They may include, but not limited to, the interference with placental nuclear receptors, such as peroxisome proliferator activated receptors, estrogen receptors, thyroid hormone receptors, and aromatic hydrocarbon receptor, induction of oxidative stresses in placenta, changes of placental levels of cytokines and chemokines, and changes of DNA methylation or microRNAs profiles. A number of important knowledge gaps were also identified in order to further facilitate the understanding of placenta-mediate peri- and postnatal effects of environmental chemicals, which include, but are not limited to, potential cocktail effects on placenta from prenatal exposure to a large complexity of environmental chemicals, sex-specific effects of environmental chemicals on the placenta, the mediation of placenta in the cause-effect relationships between environmental exposure and APOs, and the chemical-dependent sensitive window of exposure.

Graphical Abstract

Keywords:

• Environmental chemicals
• placental exposure
• placental development
• adverse pregnancy outcomes

Handling Editors:

• Lena Q. Ma and Robert J. Letcher

Disclosure statement

The authors declare that they have no competing interests.

Additional information

Funding

The present study was financially supported by the National Natural Science Foundation of China (No. 42107449, 41977373, and 42111530087), Guangdong (China) Basic and Applied Basic Research Foundation (No. 2022A1515011914), Guangdong (China) Innovative and Enterpreneurial Research Team Program (No. 2016ZT06N258), and Research Foundation – Flanders (FWO) (project number VS02621N).