Prenatal Bisphenol-A exposure affects fetal length growth by maternal glutathione transferase polymorphisms, and neonatal exposure affects child volume growth by sex: From multiregional prospective birth cohort MOCEH study
Graphical abstract
Introduction
Humans are influenced by the environment throughout their lives. Furthermore, it has recently been reported that prenatal settings through the maternal condition as well as the placenta can be affected by nutrients and numerous environmental factors such as heavy metal (Grandjean et al., 1997), alcohol (Nancy et al., 1989), air pollutants (Kim et al., 2014) and psychosocial status (Oberlander et al., 2014), as well. Bisphenol-A (BPA) is a synthetic material that affects people throughout their environment. BPA is an estrogen-mimicking, endocrine-disrupting chemical that is used mainly in the production of polycarbonate plastic and epoxy resins used in plastic ware, food-can linings and dental sealants (Atkinson and Roy, 1995). Recently, the effects of BPA exposure in adults and children have been positively correlated with higher BMI or weight, depending on the dose of BPA exposure (Wang et al., 2012; Braun et al., 2014). In addition, many studies have been conducted on the effects of BPA exposure on the fetus during pregnancy (Casas et al., 2016, Snijder et al., 2013). However, the relationship between BPA and the fetal or neonatal growth indexes are inconsistent, and there is not enough research to clarify if exposure to BPA during pregnancy affects only the fetal growth at the time of exposure, or if it affects postnatal growth. Previous studies have indirectly estimated the amount of BPA exposed to the fetus through maternal urine BPA concentration analysis during pregnancy. However, according to a study by Ikezuki et al. (2002), the highest concentration of BPA was detected in the amniotic fluid, therefore BPA exposure to the infant through the placenta may be much higher than was expected from only measuring the maternal urine samples. Meanwhile, glutathione transferases (GSTs) are a major group of detoxification enzymes involved in cellular defense against oxidative stress. There are several isoenzymes in the superfamily of GSTs: alpha (GSTA), mu (GSTM), omega (GSTO), pi (GSTP), theta (GSTT), and zeta (GSTZ). Among these, GSTM1 and GSTT1 are encoded by different genes located on the chromosomes 1p13.3 and 22q11.33 respectively. The GSTM1 and GSTT1 genes have the null allele variants and the null genotypes for both enzymes result in no enzyme activity (Lu et al., 2014). In a study of Korean adults, there was a positive association between total urinary BPA concentration and oxidative stress markers, such as the reactive oxygen species malondialdehyde (MDA) and 8-hydoxydeoxyguanosine (8-OHdG) (Hong et al., 2009). In other multivariate studies, higher BPA levels in postmenopausal women were correlated with higher MDA, 8-OHdG and CRP, suggesting that postmenopausal women may be more sensitive to the effects of BPA than premenopausal women and men (Yang et al., 2009). These results suggest that BPA exposure in humans may cause oxidative damage in the long term. To understand the effects of BPA on oxidative damage, we investigated the effect of BPA on maternal GSTs polymorphisms. In this study, BPA exposure was estimated through maternal and neonatal urine samples within 3 weeks after birth, considering the overall BPA exposure to the fetus via the placenta. Additionally, the relationship between BPA exposure and fetal/postnatal growth indexes were investigated for 72 months after birth.
Section snippets
Data collection and participants
This study was conducted as a part of the Mothers and Children's Environmental Health (MOCEH) study, which is a multiregional prospective cohort study. To investigate the effects of environmental materials on fetal and postnatal development, the MOCEH study was established in 2006, and the design has been previously described in other articles (Kim et al., 2009). Three regional centers were located in the cities of Seoul, Cheonan, and Ulsan cities, and all pregnant women who lived in these
Characteristics of participants
Participant characteristics and the geometric mean level of BPA concentration/creatinine with each period are described in Table 1. The geometric mean BPA concentration/Cr were 1.26 μg/g Cr in the third trimester and 12.81 μg/g Cr at neonatal period. The proportions of each covariate were different, but each BPA concentration/creatinine produced similar values, except with regard to family income and fetal sex in the third trimester. The difference in BPA concentration between the groups was
Discussion
In this study, we considered the effects of exposure to BPA, estimated by maternal and neonatal urinary BPA concentration, on growth outcome in fetal and early childhood. This study suggests that BPA exposure affects fetal and postnatal growth outcome depending on the timing of its exposure, and furthermore, the susceptible period for prenatal BPA may be the third trimester, as compared to the second. In the fetal period, maternal BPA exposure in the third trimester affects fetal femur length
Conclusions
Our study suggests that BPA exposure has a negative association with intrauterine length growth, but has a positive association with volume growth after birth. Furthermore, intrauterine growth restrictions were affected by maternal GSTs polymorphisms, and weight gain during childhood was affected by infant sex. Therefore, we recommend that future studies consider not only specific adiposity assessment, but also the relationship between BPA and puberty development in adolescents.
Declaration of interest
The authors declare no competing interest.
Abbreviations
BPA Bisphenol-A
GST glutathione transferase
LMM linear mixed model
Role of the funding source
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Acknowledgments
This study was supported by the MOCEH (Mothers and Children's Environmental Health) project of the National Institute of Environmental Research, Republic of Korea.
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