Active Pregnancy, Children & Inherited Conditions Diabetes, Hormones & Metabolism

Exploring mechanisms of placental toxicity following xenobiotic exposure

Funder BBSRC (part of UKRI)
Recipient organisation University of Cambridge
Funding Not disclosed
Period Apr 2025 — Apr 2029

In plain English

AI plain-English summary

The placenta is routinely ignored in safety testing of drugs and environmental chemicals, even though substances circulating in a pregnant woman’s blood can accumulate there and disrupt its function. This matters because a damaged placenta can harm fetal development and affect the child’s health long after birth. Current toxicology studies rarely examine the placenta directly, leaving a blind spot in how we assess chemical risks during pregnancy. The researchers will use human placental cells grown in 3D cultures to systematically measure how various foreign compounds affect cell survival, nutrient uptake, hormone production, and other key functions. They will also test whether combinations of chemicals produce stronger effects than single exposures. If successful, this work could provide regulators and pharmaceutical companies with reliable methods to screen drugs and environmental contaminants for placental toxicity before they reach pregnant women. The project is fundamental science—it aims to uncover the biological mechanisms by which chemicals alter placental cells, including changes in metabolism, oxidative stress, and inflammation. That mechanistic understanding is a necessary foundation for building better safety guidelines and, eventually, protecting pregnancies from avoidable chemical harm.

View original technical description
Assessing the impacts of xenobiotics on human placenta development and function. As the placenta is perfused with maternal blood, xenobiotics circulating in the mother easily reach the placenta. These can accumulate and compromise placental formation and function with consequences for fetal development, and subsequent adult health. Despite this, the placenta remains largely ignored in traditional toxicology studies. This joint project will exploit the Sferruzzi-Perri lab's expertise in placental physiology and Dr. Wolton's experience in developmental and reproductive toxicology. The project will utilise human trophoblast cell models including 3D cultures to systematically assess the impacts of xenobiotics on viability, cytotoxicity, differentiation, nutrient uptake, and hormone secretion. The potential for synergistic or additive toxicity based on co-exposures with xenobiotics will also be studied. Toxicodynamic data will be coupled with toxicokinetic modelling to understand the exposure conditions required to elicit functional effects on human trophoblast cells. Functional changes caused by xenobiotic exposure will be related to alterations in trophoblast metabolism, oxidative stress, apoptotic pathways, and inflammatory cytokine release. The mechanisms underlying trophoblast alterations will be uncovered through high throughput analyses, such as RNA-sequencing and metabolomics, with targeted validation experiments depending on the findings.

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