Serum perfluoroalkyl substances in relation to lipid metabolism in Chinese pregnant women

Highlights

• Different kinds of PFASs were widely detected in pregnant women in North China.

• Serum PFHxS was found to be positively associated with serum TC, HDL and LDL levels.

• Some PFASs showed a non-monotonic association with lipid parameters.

Abstract

Laboratory and epidemiologic studies suggested that exposure to perfluoroalkyl substances (PFASs) could affect lipid metabolisms, but data remain limited for pregnant women. A total of 436 pregnant women were selected in Tangshan City, North China. Serum levels of 11 PFASs were determined in the early term of pregnancy. Four lipids (total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL)) were measured in the late term of pregnancy. Of 11 PFASs, seven had a detection rate of greater than 70%. After adjusting for potential confounders, natural log-transformed perfluororohexanesulfonic acid (ln PFHxS) was positively associated with TC (β: 0.184, 95% CI: 0.045–0.321), HDL (β: 0.040, 95% CI: 0.001–0.083), and LDL (β: 0.091, 95% CI: 0.001–0.185). Ln perfluoroundecanoic acid (PFUdA) was positively associated with HDL (β: 0.021, 95% CI: 0.001–0.044), while Ln perfluorodecanoic acid (PFDA) was negatively associated with LDL (β: −0.053, 95% CI: −0.098∼-0.009) and ln perfluorootanoic acid (PFOA) was negatively associated with LDL/HDL (β: −0.042, 95% CI: −0.075∼-0.009). In principal component analysis, the component with a large loading of 31.3% for PFOA, perfluorononanoic acid (PFNA), PFDA and PFUdA showed a negative association with LDL/HDL. After serum concentrations of PFASs were categorized into quartiles, a higher level of TC was seen in the second quartile of PFOA or PFNA than the first quartile, but a lower LDL/HDL ratio was seen in the fourth quartile of PFOA, PFUdA or PFDA. These results suggested that exposure to PFASs has a potential to influence lipid metabolisms in pregnant women.

Introduction

Perfluoroalkyl substances (PFASs) are a class of highly stable man-made organic compounds with an aliphatic carbon backbone and all hydrogen atoms being substituted by fluorine atom (Zeng et al., 2015). PFASs have been widely used in the past several decades and are detected in a variety of environmental and biological media (Sunderland et al., 2019). Lipids are a large group of compounds, such as fatty acids, glycerolipids, and sterol lipids, which play a key role in maintaining normal human physiological functions (Shamim et al., 2018). Lipid metabolism is known to be associated with cardiovascular illness and sub-health status (Manandhar et al., 2017). However, PFASs have been reported to possibly affect lipid metabolism by multiple mechanisms, such as disruption of thyroid or estrogen functions (Kim et al., 2018; Sunderland et al., 2019; Ding et al., 2020), activation of metabolic receptors (peroxisome proliferator-activated receptor α (PPARα)), and interaction with constitutive activated receptor (CAR), pregnane X receptors (PXR) and liver X receptors (LXR) (Bijland et al., 2011). Moreover, the structural resemblance of PFASs to natural fatty acids may directly cause disorders in lipid regulation (Nelson et al., 2010).

For pregnant women, maternal hyperlipidemia is related to enhanced oxidative stress and adipocytokines have effects on fetal growth (Herrera and Ortega-Senovilla, 2010). Elevated plasma triglycerides (TG) was reported to be associated with various adverse consequences, including endothelial damage, preeclampsia and pregnancy-induced hypertension (Kaaja, 2011). Elevated total cholesterol (TC) was found to be associated with preeclampsia (Spracklen et al., 2014). Currently, seven epidemiological studies of general population or of children (Nelson et al., 2010; Wang et al., 2012; Fu et al., 2014; Zeng et al., 2015; Li et al., 2020; Lin et al., 2020; Liu et al., 2020) found that PFASs exposure was associated with blood lipid levels, including TC and TG. However, only four studies investigated the relationship between PFAS and lipid metabolism in pregnant women, which were conducted in Denmark (Skuladottir et al., 2015), Spain (Matilla-Santander et al., 2017), Norway (Starling et al., 2014) and the U.S. (Spratlen et al., 2020). These studies reported that exposure to PFASs was associated to one or more lipids during pregnancy, but the results were inconsistent.

Multiple factors might influence the effects of exposure to PFASs on lipid metabolism during pregnancy including diet pattern, exposure level of PFASs or genetic background (Ordovas and Corella, 2005; Zili, 2017). So far, to our best knowledge, there have been no relevant studies conducted among Chinese pregnant women. In the current study, we investigated 436 pregnant women in Tangshan City, North China, and measured the serum levels of 11 PFASs and four lipids (TC, TG, high-density lipoprotein (HDL), and low-density lipoprotein (LDL)) to determine their associations.