A pilot study: bisphenol A-glucuronide and their association with sex steroid hormones and 25 Hydroxy vitamin D among mother and child pairs.

Abstract

Bisphenol A (BPA) is an endocrine disruptor that has become ubiquitous in our environment. It is utilised in numerous consumer products related to the manufacture of plastics. Exposure to BPA has been linked to a wide range of disease including disorders of immune, reproductive and neurological development as well as malignancy. The in-utero stage is particularly vulnerable to the effects of BPA exposure. Maternal exposure has been shown to be positively correlated to BPA levels in the foetus and in early infancy. There is a paucity of data on the extent of exposure to BPA in sub-Saharan populations. As an endocrine disruptor BPA has been shown to affect steroid hormone function and production. However, the mechanism of BPAs action on steroid hormones have not been fully elucidated. The objectives of this study were to describe the extent of BPA exposure in maternal-child pairs in a local cohort, to determine the effect BPA exposure on their steroid hormone concentrations and to elucidate further mechanisms of BPA action via methylation studies of promoter regions of enzymes involved in steroid metabolism. Method: Matched maternal and cord blood samples collected as part of the Maternal and Child Environment birth cohort study were utilised for the purpose of the study. BPA and its metabolite BPA glucuronide (BPA-g) were analysed in the serum maternal and cord blood samples using an in-house developed liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Samples were also analysed for nine sex steroid hormones namely-: oestradiol (E2), total testosterone (TT), 11- deoxycorticosterone (11DOC), Dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS) androstenedione (Andro), 17-OH progesterone (17OHP), dihydrosterone (DHT) and progesterone (Prog) using LC-MS/MS. 25 hydroxy-Vitamin D (D2 and D3) concentrations were determined in the study cohort using high performance liquid chromatography (HPLC). The degree of the methylation status of the promoter regions of the CYP1B1 and CYP3A4 was assessed using quantitative PCR. A p value of <0.05 was considered significant. Statistical analysis was performed on Medcalc statistical software program version 18.11 (Medcalc, Belgium). Results: Significant exposure to BPA was described in this cohort with more than 75 percent of maternal and cord blood samples exhibiting detectable BPA and/or BPA-g levels. This study demonstrated a statistically significant positive correlation of maternal BPA and BPA-g concentrations with cord blood samples as well as a significant association with cord blood oestradiol and testosterone. A significant negative relationship with cord (p=0.03) and maternal BPA-g levels (p=0.04) and cord total 25OHD levels was noted. No significant association with CYP1B1 and CYP3A4 promoter methylation status and BPA concentrations was identified. Conclusion. This study is the first in South Africa to describe the extent of BPA exposure in a human cohort and in maternal-child pairs. It is also the first in Africa and one of the few studies worldwide to describe the relationship between steroid hormones and BPA in maternal and cord blood samples. The significant BPA exposure noted in this study has important implications with regards to public health

strategies to limit BPA exposure as well as to prevent, identify and manage associated disease conditions.