Insight into a first trimester human placental mechanism of fetal endocrine disruption
Year: 2020
Type: conference-abstract
Abstract: Human chorionic gonadotropin (hCG) is a placental hormone produced during pregnancy which regulates in part the development of fetal reproductive tract. hCG is thought to mediate effects of prenatal phthalates on the fetus. We have shown previously that phthalate-hCG and hCG-neonatal genitalia associations are both sex-specific. The aim was to directly measure, within the relevant critical window in the first trimester, modification of hCG regulation by fetal sex and by phthalate levels. Placental tissue samples (N=96, 45% male) were donated by women undergoing elective pregnancy termination at 2 clinics between gestational weeks 7 - 14. Tissues were dissected, snap frozen and stored at -80 C. mRNAs were measured by qPCR: PPARG, CGA, CGB and 2 housekeeping genes, RN18S and UBP1. PPARG encodes a transcription factor that regulates expression of hCG (encoded by CGA and CGB). Quantitation was done by relative standard curve. Sex was determined by measuring 2 Y-linked genes by PCR. All data were normalized, transformed, and analyzed using linear regression. Placental phthalate levels in the same sample set are being analyzed currently. There was no difference in the means of mRNAs between male and female fetuses. We measured a strong interaction of PPARG and fetal sex in the correlation of PPARG and CGA/CGB (p-interaction<0.005). In male placentas, one log10 unit in PPARG was associated with a 2.53 (95% CI 1.80, 3.26) log10 increase in CGA and CGB levels. In female placentas, the same association was null (β= 0.37 log10 units, 95% CI -0.32, 1.05). Associations with placental phthalate levels are forthcoming. These data offer novel insight into the basis for commonly reported sex-specific associations between prenatal phthalates and child health outcomes. hCG offers promise as a molecular biomarker that can conceptually and quantitatively connect sex-specific effects of prenatal exposures on placental mechanisms, and on fetal outcomes.
Source: ISEE Conference Abstracts
Authors: M. Smith, N. Snyder, R. Birru, J.J. Adibi
Institutions: University of Pittsburgh, Drexel University
Language: English
Subfield: Health, Toxicology and Mutagenesis
Field: Environmental Science
Domain: Physical Sciences
Open Access status: diamond
OpenAlex ID: W3168413441