Differences in testosterone and its precursors by sex of the offspring in meconium

Abstract

Prenatal metabolism exerts profound effects on development. The first stool of the newborn, meconium, provides a window into the prenatal metabolic environment. The objective of this study was to examine the feasibility of meconium as a novel matrix to quantify prenatal steroid levels. We quantified parameters of analytical interest regarding the use of meconium, including sample stability. We hypothesized that meconium steroid content would differ by sex, prompting analysis of meconium to test effects of prenatal steroid metabolism. Meconium from 193 newborns enrolled in the Early Autism Risk Longitudinal Investigation (EARLI) study, including 107 males, and 86 females, were analyzed by isotope dilution-liquid chromatography-high resolution mass spectrometry (ID-LC-HRMS) while blinded to identity for testosterone (T), androstenedione (AD), and dehydroepiandrosterone (DHEA). Steroids levels were compared by sex, and investigations of potential trends resulting from sample storage or processing was conducted. The unconjugated steroid content of meconium in ng/g (mean, standard deviation) was for males: T (2.67, 8.99), AD (20.01, 28.12), DHEA (13.96, 23.57) and for females: T (0.82, 1.63), AD (22.32, 24.38), DHEA (21.06, 43.49). T was higher in meconium from males (p = 0.0333), and DHEA was higher in meconium from females (p = 0.0202). 6 female and 3 male T values were below the limit of detection. No extreme variability in hydration or trend in steroid levels by storage time was detected. Sexually dimorphic levels of hormones may reflect gestational differentiation, and future studies should consider meconium analysis.

Identification and Quantification of Paclitaxel and its Metabolites in Human Meconium from Newborns with Gestational Chemotherapeutic Exposure

“…This has been used to quantify maternal use of drugs of abuse and environmental exposures during pregnancy 14 , anti-retroviral pharmacokinetics 18 , metabolomics during gestational diabetes 19 , and fetal sex steroid metabolism 20 . To our knowledge, this is the first meconium report of the transplacental pharmacokinetics of chemotherapeutics in humans.…”

“…Since starting the current project, 30 women have enrolled and received chemotherapy, and 23 have agreed to collect meconium at the time of delivering their child. The majority of women in the study (20) were treated for breast cancer, 1 for colon cancer and 2 for Hodgkin's Lymphoma. As the study is ongoing, full un-blinding of treatment regimens is not possible.…”

Meconium androgens are correlated with ASD-related phenotypic traits in early childhood

“…Other studies using either amniotic fluid or cord blood reported mixed, but mostly null results. (24)(25)(26)(27) To overcome the limitations of amniocentesis and cord blood, we used meconium, the first stool of a newborn, to estimate prenatal androgen exposure. Since formation of meconium is thought to start around the 12-13 th week of gestation, and meconium can be non-invasively collected within 72 hours of the birth of the child, meconium has the potential to capture cumulative prenatal exposure.…”

“…Since formation of meconium is thought to start around the 12-13 th week of gestation, and meconium can be non-invasively collected within 72 hours of the birth of the child, meconium has the potential to capture cumulative prenatal exposure. (28). Previous studies have utilized meconium samples to examine prenatal exposure to both exogenous and endogenous compounds, (29)(30)(31) and we recently developed a robust method to quantify androgens in human meconium.…”

“…Previous studies have utilized meconium samples to examine prenatal exposure to both exogenous and endogenous compounds, (29)(30)(31) and we recently developed a robust method to quantify androgens in human meconium. (28) This study investigated the association between levels of androgens, namely, testosterone (T) and its weakly androgenic precursors, dehydroepiandrosterone (DHEA) and androstenedione (A4), measured in meconium, and autistic traits at 12 and 36 months of age. Since these steroids exist in both unconjugated and glucuronide and/or sulfate-conjugated forms, and previous research has suggested glucuronidation may be different in autistic individuals, (32) we performed analysis on both unconjugated (u) and total (t) forms that include both conjugated and unconjugated.…”