Maintaining thyroid homeostasis during pregnancy is vital for fetal development. The few studies that have investigated associations between metal exposure and gestational thyroid function have yielded mixed findings. To evaluate the association of exposure to a mixture of toxic metals with thyroid parameters in 824 pregnant women from the Rhea birth cohort in Crete, Greece. Concentrations of three toxic metals [cadmium (Cd), antimony (Sb), lead (Pb)] and iodine were measured in urine using inductively coupled plasma mass spectrometry and thyroid hormones [Thyroid Stimulating Hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3)] were measured in serum in early pregnancy. Associations of individual metals with thyroid parameters were assessed using adjusted regression models, while associations of the metal mixture with thyroid parameters were assessed using Bayesian Kernel Machine Regression (BKMR).Women with high (3rd tertile) concentrations of urinary Cd, Sb and Pb, respectively, had 13.3 % (95%CI: 2.0 %, 23.2 %), 12.5 % (95%CI: 1.8 %, 22.0 %) and 16.0 % (95%CI: 5.7 %, 25.2 %) lower TSH compared to women with low concentrations (2nd and 1st tertile). In addition, women with high urinary Cd had 2.2 % (95%CI: 0.0 %, 4.4 %) higher fT4 and 4.0 % (95%CI: −0.1 %, 8.1 %) higher fT3 levels, and women with high urinary Pb had 4 % (95%CI: 0.2 %, 8.0 %) higher fT3 levels compared to women with low exposure. The negative association of Cd with TSH persisted only when iodine sufficiency was unfavorable. BKMR attested that simultaneous exposure to toxic metals was associated with decreased TSH and increased fT3 and revealed a potential synergistic interaction of Cd and Pb in association with TSH. The present results suggest that exposure to toxic metals even at low levels can alter gestational thyroid homeostasis.

The presence of polycyclic aromatic hydrocarbons (PAHs) in the fetal environment is a high-priority concern due to the fetus being more sensitive than adults to these ubiquitous xenobiotics. The aim of the present study was to compare the maternal and fetal serum levels of ΣPAHs and their effects on fetal growth in an industrial and an urban area in Southwest Iran. The industrial area was the petrochemical and gas area (PGA) of the Central District of Asaluyeh County and the urban area (UA) was the Central District of Bushehr County, Ninety-nine maternal serum (MS) and 99 cord serum (CS) samples from the PGA and 100 MS and 100 CS samples from the UA were collected during May 2018 to February 2019. The mean concentrations of ΣPAHs were significantly (p < 0.05) higher in the PGA than the UA in both MS (157.71 vs. 93.56 μg/L) and CS (155.28 vs. 93.19 μg/L) samples. Naphthalene (NAP) was the predominant PAH detected in all the studied samples. Significant negative associations were found between birth weight and anthracene (ANT) level in MS (β = −22.917, p = 0.032; weight decrement = 22.917 g for a 1 μg/L increase in ANT); head circumference and chrysene (CHR) level in MS (β = −0.206, p = 0.023; head circumference decrement = 0.206 cm for a 1 μg/L increase in CHR); and birth height and NAP level in CS (β = −0.20, p = 0.005; height decrement = 0.20 cm for a 1 μg/L increase in NAP). Maternal diet had a significant effect on the serum levels of PAHs. The results of this study showed that transmission of PAHs from mother to fetus through the cord blood is an important issue and mothers who live in industrial areas and consume PAH-containing foodstuffs, and their fetuses, are more at risk than those living in a non-industrial urban area.

Triclosan (TCS) and Triclocarbon (TCC) are chlorinated synthetic antimicrobial agents formaternal urinelated in quantities of consumer products. However, the biomonitoring of direct exposure reflection for fetuses are rare. In this study, we determine the concentrations of TCS and TCC in paired maternal serum, cord serum, maternal urine, and amniotic fluid samples collected from a cohort of 95 expecting mother-fetal pairs in Southern China. TCS and TCC are detected widely (detection rates: >76.9%) in maternal serum, cord serum, maternal urine, and amniotic fluid samples. TCS is found to be the predominant antimicrobial agent with median concentrations in maternal serum (1.5 ng/mL) and cord serum (1.8 ng/mL) that are one order of magnitude higher than those of tcc in maternal serum (0.085 ng/mL) and cord serum (0.052 ng/mL), respectively. Cord serum concentrations of tcs and tcc correlated well with the concentrations in maternal serum, which reflect the mothers’ contribution to fetal exposure. The higher median ratio of cord serum/maternal serumTCS (0.95) compared to that of cord serum/maternal serumTCC (0.53) indicates high placental transmission ability of TCS. Moreover, the facility to penetrate the placental barrier and hard to depurate characteristics lead to the long residence of TCS in the fetal environment, causing great concern over the prenatal exposure risks during the critical window of fetal development. This study provides a novel contribution by increasing existing knowledge on the exposure assessment of TCS and TCC during pregnancy through the exploration of matched maternal-fetal samples.

The placenta is essential for sustaining the growth of the fetus. The aim of this study was to investigate the role of the placenta in MCLR-induced significant reduction in fetal weight, especially the changes in placental structure and function. Pregnant mice were intraperitoneally injected with MCLR (5 or 20 μg/kg) from gestational day (GD) 13 to GD17. The results showed MCLR reduced fetal weight and placenta weight. The histological specimens of the placentas were taken for light and electron microscopy studies. The internal space of blood vessels decreased obviously in the placental labyrinth layer of mice treated with MCLR. After the ultrastructural examination, the edema and intracytoplasmic vacuolization, dilation of the endoplasmic reticulum and corrugation of the nucleus were observed. In addition, maternal MCLR exposure caused a reduction of 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) expression in placentae, a critical regulator of fetal development. Several genes of placental growth factors, such as Vegfα and Pgf and several genes of nutrient transport pumps, such as Glut1 and Pcft were depressed in placentas of MCLR-treated mice, however nutrient transporters Fatp1 and Snat4 were promoted. Moreover, significant increases in malondialdehyde (MDA) revealed the occurrence of oxidative stress caused by MCLR, which was also verified by remarkable decrease in the glutathione levels, total antioxidant capacity (T-AOC) as well as the activity of antioxidant enzymes. Real-time PCR and western blot analysis revealed that GRP78, CHOP, XBP-1, peIF2α and pIRE1 were remarkable increased in placentas of MCLR-treated mice, indicating that endoplasmic reticulum (ER) stress pathway was activated by MCLR. Furthermore, oxidative stress and ER stress consequently triggered apoptosis which contributed to the impairment of placental development. Collectively, these results suggest maternal MCLR exposure results in reduced fetal body weight, which might be associated with ROS-mediated endoplasmic reticulum stress and impairment in placental structure and function.

Previous in vitro studies have implied that triphenyl phosphate (TPHP) may act as an obesogen. However, its specific contributions to the progression of obesity and related metabolic diseases are still unclear in vivo in mice. In this study, we evaluated the effects of in utero and lactational exposure to three doses of TPHP (10, 100, and 1000 μg/kg BW) on obesity and metabolic dysfunctions in adult male mice fed a low-fat diet (LFD) or high-fat diet (HFD), by examining body weight, liver weight, histopathology, blood biochemistry, gene expression, and gut microbiota compositions and metabolic functions. Results showed that TPHP exposure led to increased body weight, liver weight, fat mass, hepatic steatosis, impaired glucose homeostasis, and insulin resistance, and mRNA levels of genes involved in lipid metabolism, especially lipogenesis and lipid accumulation, were significantly altered by TPHP treatment. Gas chromatography-mass spectrometry (GC-MS) analysis further supported the changes in fatty acid composition. Intestinal flora measurements by 16S rRNA gene sequencing and ¹H NMR based fecal metabolomics indicated that TPHP treatment modulated gut microbiome composition and influenced host-gut co-metabolism, especially for bile acids and short chain fatty acids (SCFAs). These results suggest that fetal exposure to TPHP can promote the development of obesity and metabolic dysfunctions in adult mice.

Perfluorooctane sulfonate (PFOS), a hepatic toxicant and a potential hepatocarcinogen, is commonly used in industrial products. The widespread contamination of PFOS in human maternal and cord blood has raised concerns about its potential risks to the fetus. It is believed that adverse environmental exposure during the critical period of embryo development can have long-lasting consequences in later life. In this report, we used transcriptome sequencing, followed by bioinformatics analysis, to elucidate the potential hepatotoxic and hepatocarcinogenic effects of prenatal PFOS exposure in the fetus. Our results demonstrated that prenatal PFOS exposure could activate the synthesis and metabolism of fatty acids and lipids, leading to liver damage and interference with liver development in the fetus. In addition, a number of cancer-promoting signaling pathways, including Wnt/β-catenin, Rac, and TGF-β, were found to be activated in the fetal liver. More importantly, hepatic transaminase activity, including aspartate aminotransferase and alanine transaminase activity, was induced in the liver of mice offspring after prenatal PFOS exposure. For the first time, our results demonstrate that the hepatotoxic effects of prenatal exposure to PFOS may predispose to a long-term liver disorder in the offspring.

To Date, the knowledge on relationship between PCBs/PBDEs exposure and thyroid hormones (THs) levels during pregnancy still needs to be extended. Meanwhile, studies on congener-specific adipose-serum ratios for PCBs/PBDEs were limited. This study reports the levels of PCBs/PBDEs in serum-adipose tissue samples (n = 64) from expectant women living surrounding e-waste recycling sites in Wenling, China. Their concentrations varied from several to hundreds of ng g−1 lipid. Maternal exposure to PCBs was associated with lower TSH during pregnancy, suggesting possible implication for maternal health and fetal development. The compound levels between the adipose tissue and matched serum samples were highly correlated (p < 0.001), generating a predicted adipose-serum partitioning relationship for individual PCB congener and PBDE congener. Molecular characteristics, such as Kow value, molecular weight and molecular volume, may play a key role in the variable partitioning of some compounds between serum and adipose tissue.

During pregnancy, human exposure to endogenous estrogens and xenoestrogens (such as lignans) may comprehensively impact the gestational maintenance and fetal growth. We measured the concentrations of 5 lignans and the profile of 13 estrogen metabolites (EMs) in the urine samples of 328 pregnant women and examined their associations with birth outcomes. We found significantly positive associations between gestational age and urinary matairesinol (MAT), enterodiol (END) and enterolactone (ENL), as well as 16-hydroxylation pathway EMs. There were consistently positive relationships between END and the 16-hydroxylation pathway EMs. The positive relationships of MAT, END and ENL exposures with the length of gestation were mainly in the low exposure strata of the levels of these EMs. This study reveals that MAT, END and ENL as well as 16-hydroxylation pathway EMs are associated with birth outcomes, and that there are interactive relationships between lignans and 16-hydroxylation pathway EMs with birth outcomes.

Prenatal perfluoroalkyl substance (PFAS) exposure has been linked to adverse birth outcomes, but the underlying mechanism has yet to be elucidated. DNA methylation changes in mesoderm-specific transcript (MEST) imprinted gene may be a mechanism of the prenatal exposure effects of PFASs on fetal growth. The aim was to investigate the prenatal PFASs exposure effects on DNA methylation changes in MEST imprinted gene involved in fetal growth. Among 486 mother-infant pairs from the Taiwan Birth Panel Study, PFASs and DNA methylation levels at 5 CpG sites of MEST promoter region were measured in cord blood. Univariable and multivariable linear regressions were performed to estimate the associations between prenatal PFAS exposure, MEST DNA methylation levels, and child birth outcomes. Mediation analysis was performed to examine the potential pathway of MEST methylation between PFASs and birth outcomes. We found that higher prenatal perfluorooctyl sulfonate (PFOS) exposure was significantly associated with lower methylation levels at 5 CpG sites of MEST promoter region (an adjusted β range: −1.56, −2.22). Significant negative associations were also found between MEST methylation levels and child birth weight. Furthermore, the associations between PFOS and perfluorooctanoic acid (PFOA) exposure and MEST methylation levels were more profound in girls than in boys. The mediated effect of average MEST methylation level between PFOS exposure and birth weight was 18.3 (95% CI = 2.1, 40.2; p = 0.014). The direct effect of PFOS exposure to birth weight independent to average MEST methylation level was −93.2 (95% CI = −170.5, −17.8; p = 0.018). In conclusion, our results suggest that prenatal PFAS exposure, especially PFOS, is associated with lower methylation levels at MEST promoter region, which not only leverages the role of imprinted gene in ensuring the integrity of fetal growth but also provides a potential mechanism for evaluating the prenatal exposure effect.

Isoflavones (ISOs) are naturally occurring endocrine-disrupting compounds. Few human studies have evaluated the effects of ISO exposure on neonatal anthropometry. This study aimed to examine the associations of maternal soy product consumption and urinary ISO concentrations, including genistein, daidzein, glycitein, and equol, with neonatal anthropometry, based on a Chinese cohort study. In Shanghai-Minhang Birth Cohort Study, pregnant women at 12–16 weeks of gestation were recruited, and they completed a structured questionnaire to assess soy product consumption during pregnancy. They also provided a single spot urine sample for the ISO assay. Neonatal anthropometric indices (birth weight; arm, waist, and head circumference; and triceps, back, and abdominal skinfold thickness) were measured at birth. Multivariable linear regression analysis was performed among the 1188 mother-infant pairs to examine the associations between maternal soy product consumption and neonatal anthropometry. The same statistical model was applied to examine the associations between maternal ISO exposure and neonatal anthropometry among 480 mother-infant pairs. Neonate girls born to mothers who “sometimes” and “frequent” consumed soy products had 169.1 g (95% confidence interval [CI], −68.9–407.1) and 256.5 g (95% CI, 17.1–495.8) higher birth weight, respectively, than those born to mothers who “never” consumed soy products during pregnancy. We observed consistent associations between higher maternal urine ISO concentrations and increased anthropometric indices (birth weight, arm and waist circumference, and triceps and abdominal skinfold thickness) in neonate girls, while no association was observed among boys. The findings suggested that maternal dietary ISO intake during pregnancy is associated with fetal development in a sex-specific pattern. In addition, follow-up studies are required to evaluate whether the observed changes in anthropometric indices at birth are associated with health conditions later in life.