# Placental origins of phthalate-induced changes in fetal reproductive development

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $559,695

## Abstract

Summary/Abstract: Ubiquitous chemical exposures during pregnancy have escalated to the level where
phthalates and other endocrine disrupting chemicals (EDCs) may be reducing fertility in current and in future
generations. Several human studies have shown relationships between higher adult phthalate exposure and
reduced fertility in men and women. Extensive evidence from animal studies indicate that phthalates can
cause defects in the developing reproductive system (ovaries, testes, genitalia) of the fetus. However, attempts
to understand if the human fetus is similarly vulnerable have not been successful. This may be due to the
omission of the human placenta in these studies. The placenta plays an important, species-specific and sex-
specific role in responding to maternal phthalate exposures and directing the sexual differentiation of the fetus.
The proposed project will evaluate the role that the human placenta may play in mediating the effects of
phthalates on fetal reproductive system development in early human pregnancy (i.e. fetal origins of infertility).
Aim 1 will compare phthalate concentrations in matched placental tissue/maternal urine to determine if
standard biomarkers of phthalate exposure in maternal urine are representative of placental phthalate
concentrations, more proximal to the fetus. The placental tissue and maternal urinary metabolomes (an
unbiased analysis of 10,000 endogenous metabolites) will be correlated with phthalate levels in order to
identify novel biomarkers of phthalate exposure, metabolism, and sex-specific fetal effects. Aim 2 will use
human primary tissue culture models to re-establish communication between the placenta and the fetal gonad
ex vivo. Placental 3D cultures will be dosed with phthalate concentrations equivalent to those measured in
placental tissue. The secreted placental proteins from these experiments will then be placed on 3D fetal
gonads (+/- phthalates, +/- placental proteins), matched by sex and gestational age. We will determine if and
how fetal steroidogenesis is altered by phthalates exposure, via the placenta. Aim 3 will translate these
findings to 500 pregnancies in two existing longitudinal birth cohorts. First, we will measure a panel of
placenta-, phthalate-, and sex- specific biomarkers in the first trimester. We will calculate their associations
with neonatal anogenital distance at birth (a marker of future fertility), and to birth size and neonatal adiposity
(markers of general placental function and also relevant to the future health of the child). Finally, statistical
techniques will be applied to estimate the degree to which the phthalate associations with reproductive system
development are mediated by phthalate effects on the early placenta. Greater knowledge of early pregnancy
exposures, effects, and specific ways to assess placental-fetal well-being open the possibility to move prenatal
screening earlier, incorporate assessment of environmentally-induced risks and potential...

## Key facts

- **NIH application ID:** 10151613
- **Project number:** 5R01ES029336-04
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Jennifer Joan Adibi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $559,695
- **Award type:** 5
- **Project period:** 2018-07-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10151613

## Citation

> US National Institutes of Health, RePORTER application 10151613, Placental origins of phthalate-induced changes in fetal reproductive development (5R01ES029336-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10151613. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*