# Placental iron transport under maternal stress: a missing link in foetal programming and mental health

## TL;DR

Stress during pregnancy may disrupt iron transport to the fetus, especially in females, potentially affecting long-term mental health.

## Contribution

The study reveals a sex-specific effect of maternal stress on placental iron transport, a previously unexplored interaction.

## Key findings

- Stress increased placental iron uptake but reduced fetal iron transfer.
- This effect was observed only in females and replicated in vitro with stress and dexamethasone.
- The findings suggest a new pathway linking prenatal stress to offspring mental health risks.

## Abstract

Environmental stress and iron deficiency are increasingly recognised as prevalent challenges during pregnancy, with significant implications for both maternal and foetal health. Environmental stressors such as chronic maternal anxiety can elevate cortisol levels and trigger inflammatory responses which might subsequently disrupt foetal brain development. Concurrently, iron deficiency during critical windows of gestation can hinder the formation of brain structures and neurotransmitter systems vital for emotional regulation and cognitive function after birth. Iron deficiency and exposure to stress are among the most prevalent nutritional and environmental challenges during pregnancy, and their combined influence may substantially increase the risk of neuropsychiatric disorders in the offspring. Although the individual effects of each factor are relatively well understood, their interaction during gestation remains unexplored.

In the present study, we employed human placental samples from mildly stressed and non-stressed mothers, a chronic environmental stress mouse model, and advanced in vitro techniques to examine whether gestational environmental stress alters placental iron transport.

Our findings indicate that stress enhanced placental iron uptake and accumulation, but paradoxically reduced iron transfer to the foetus—an effect observed exclusively in females and reproducible in vitro following both stress exposure and dexamethasone treatment.

These results provide insights into the sex-specific impact of environmental stress on placental and foetal iron availability and highlight a previously unrecognised pathway through which prenatal stress could influence long-term health trajectories in the offspring.

This study was supported by the 10.13039/501100001711Swiss National Science Foundation (SNF grant no. 310030_197408), the 10.13039/100000001Swiss National Science Foundation via the 10.13039/501100023650National Center of Competence in Research (NCCR) TransCure, 10.13039/100009068University of Bern, Switzerland (grant no. 51NF40_185544) and the Swiss 3R Competence Centre (3RCC; grant no OC-2019-019). TF was supported by the 10.13039/100009070Hans Sigrist Foundation, Switzerland.