Phthalate Metabolites in Maternal and Cord Plasma and Their Relations to Other Selected Endocrine Disruptors and Steroids

Abstract

Endocrine disruptors (EDs) are known to have harmful effects on the human endocrine system; special effort is actually given to the exposure during pregnancy. Humans are usually exposed to a mixture of EDs, which may potentiate or antagonize each other, and the combined effect may be difficult to estimate. The main phthalate monoesters monoethyl-, mono-n-butyl-, monoisobutyl-, monobenzyl-, mono-(2-ethylhexyl)-, mono-(2-ethyl-5-hydroxyhexyl)- and mono-(2-ethyl-5-oxohexyl) phthalate were determined in 18 maternal (37th week of pregnancy) and cord plasma samples using liquid chromatography-tandem mass spectrometry. Previously determined levels of selected bisphenols, parabens and steroids were also considered in this study. In cord blood, there were significantly higher mono-n-butyl phthalate levels than in maternal blood (p=0.043). The results of multiple regression models showed that maternal plasma phthalates were negatively associated with cord plasma androstenedione, testosterone and dehydroepiandrosterone and positively associated with estradiol and estriol. For estriol, a cumulative association was also observed for Σbisphenols. To the best of our knowledge, this is the first pilot study evaluating the effect of prenatal exposure by multiple EDs on newborn steroidogenesis. Our results confirmed phthalate accumulation in the fetal area and disruption of fetal steroidogenesis. This preliminary study highlights the negative impacts of in utero EDs exposure on fetal steroidogenesis.

The Endocrine Disruption of Prenatal Phthalate Exposure in Mother and Offspring

“…The effects of maternal phthalate exposure on fetal reproductive hormones are conflicting. Maternal plasma phthalate levels during pregnancy in the third trimester were negatively correlated with cord blood DHEA, androstenedione, and testosterone, while positively associated with estradiol and estriol (31). However, associations between maternal serum MEHP levels and the high levels of DHEA and high ratios of DHEA/androstenedione in cord serum were reported later (32).…”

“…Reproductive system is the main targets of phthalates, especially in males. Multiple research studies have reported the associations between intrauterine phthalate exposure and reproductive hormones in cord blood (29)(30)(31)(32) and amniotic fluid (33), which provided evidence that maternal phthalate exposure could affect fetal sex steroid hormones status. The explanation for this may be that phthalates disrupt the function of Leydig and Sertoli cells in testis (4).…”

Metabolic Cooperation in the Ovarian Follicle

“…Similarly, bisphenol S (BPS) causes a failure of microtubule formation and disrupts cumulus cells expansion (Zalmanova et al 2017). The impact of endocrine disruptors on newborn steroidogenesis was shown in a study of Kolatorova et al (2018), which confirmed accumulation of phthalate in the fetal area via measurements in maternal plasma and in the cord blood of their newborns. These facts taken together have a significant impact on quality of oocytes and success of human reproduction.…”

Environmental contaminants and male infertility: Effects and mechanisms

“…Several animal studies have been conducted to examine the deleterious effects of various environmental toxicants on male fertility and decipher their possible mechanism(s) of action (Akarca-Dizakar et al, 2019;Albert, Nardelli, Lalancette, Hales, & Robaire, 2018;Aydin & Erkan, 2017;Campos et al, 2019;Kim, Cheon, Choi, & Lee, 2019;Kolatorova et al, 2018). The focus of this review is to shed light on the impact of environmental contaminants on male reproduction and the underlying mechanism of action based on the recent scientific data available.…”