Exposure to air pollution before or during pregnancy alters structure of placenta

Alterations caused by fine particles can limit fetal nutrition and growth, according to study by Brazilian researchers.

By Elton Alisson  |  Agência FAPESP – Exposure of pregnant women to air pollution influences fetal development. The problems this exposure can cause range from low birth weight to a heightened possibility of certain diseases in adulthood, according to studies performed in Brazil and elsewhere. However, the molecular mechanisms underlying the impact of pollution during pregnancy have never been completely elucidated.

Now a group of researchers at the University of São Paulo’s Medical School (FM-USP) in Brazil have found that exposure to atmospheric pollutants before or during pregnancy can alter certain characteristics of the placenta, cause disturbances in a hormone system relating to uteroplacental blood flow, and reduce levels of factors involved in the process of placental formation.

The results of the study, performed as part of a Thematic Project and Sônia de Fátima Soto’s PhD research, which was conducted with a scholarship from FAPESP, were recently published in the journal PLOS ONE.

“We observed that exposure to pollutants before and/or during pregnancy triggers certain inflammatory phenomena during the placenta’s development, and these impair placental growth. This may interfere with the transfer of nutrients and oxygen from mother to fetus,” said Joel Claudio Heimann, a professor at FM-USP and Soto’s supervisor, in an interview with Agência FAPESP.

The researchers performed an experiment in which female Wistar rats – an albino strain of the species Rattus norvegicus – were exposed to both filtered air and polluted air containing 600 micrograms of fine particulate matter (between 2.5 and 10.0 micrometers) per cubic meter. They used a device called a Harvard Ambient Particle Concentrator for this purpose. Particle size was chosen on the basis of real environmental exposure in metropolitan São Paulo.

The rats were divided into four groups. A control group was exposed to filtered air before and during pregnancy. The second group was exposed to filtered air before pregnancy and polluted air during pregnancy. The third group was exposed to polluted air before pregnancy and filtered air during pregnancy. The fourth group was exposed to polluted air both before and during pregnancy.

To simulate conditions for women living in cities like São Paulo, nine-week-old female rats were exposed to polluted air five times per week for three weeks before pregnancy, resulting in 15 days of exposure, and/or seven times per week during pregnancy, resulting in 14 days of exposure. 

Placentas were collected on the nineteenth day of pregnancy, dissected and weighed to measure the effects of pollutants on placental structure and the uteroplacental renin-angiotensin system (RAS), a hormone system that plays an important role in regulating blood pressure and fluid balance.

The analysis showed that exposure to polluted air before and/or during pregnancy reduced placental mass, size and surface area and caused alterations in the RAS.

Previous studies had shown that disorders of the RAS may lead to reduced uteroplacental blood flow. In addition, angiotensin II (a peptide hormone that causes vasoconstriction and increases blood pressure) is a potent regulator of trophoblast migration and invasion early in pregnancy. 

Trophoblasts are specialized cells of the placenta, playing a major role in implantation and formation of the maternal-fetal interface. Trophoblast invasion of the maternal vasculature is a prerequisite for the establishment of normal placenta and continuation of pregnancy, the researchers explained.

“We found that exposure of pregnant rats to pollution before and/or during pregnancy caused alterations in their RAS, but further research is necessary to elucidate additional molecular mechanisms,” Heimann said.

Interference with formation of placenta 

The researchers also evaluated the effects of exposure to air pollution on factors that influence placenta formation, such as transforming growth factor beta 1 (TGFβ1) and vascular endothelial growth factor A (VEGF-A).

Several studies suggest that TGFβ1 plays a role in the invasion of the endometrium, which is the mucous membrane that lines the inside of the uterus, and that in mammals it can regulate a variety of cellular functions, including cell proliferation, differentiation, apoptosis (programmed cell death) and placental cell invasion. 

VEGF-A also plays a role in placentation, modulating angiogenesis by binding to its two receptors: fetal liver kinase 1 (Flk-1) and fms-like tyrosine kinase 1 (Flt-1). 

This study showed that exposure to air pollution lowered the levels of TGFβ1 and Flk-1 in the rats’ placentas.

Levels of angiotensin II and its receptors AT1R and AT2R were lower in the maternal portion of the placenta in the group exposed to polluted air before pregnancy and filtered air during pregnancy than in the group exposed to polluted air both before and during pregnancy. 

Levels of angiotensin II were also lower in the fetal portion of the placenta in the groups exposed to filtered air before pregnancy and to polluted air during pregnancy, to polluted air before pregnancy and filtered air during pregnancy, and to polluted air both before and during pregnancy. However, AT1R levels were higher in the group exposed to filtered air before pregnancy and polluted air during pregnancy.

Expression of the gene VEGF-A was lower in the group exposed to polluted air before and during pregnancy than in the control group.

These alterations point to possible impairment of trophoblast invasion and placental angiogenesis (formation of new blood cells), Heimann explained.

“This can have consequences for maternal-fetal interaction and limit fetal nutrition and growth,” he said.

The article “Exposure to fine particulate matter in the air alters placental structure and the renin-angiotensin system” (doi: 10.1371/journal.pone.0183314) by Sônia de Fátima Soto, Juliana Oliveira de Melo, Guilherme D’Aprile Marchesi, Karen Lucasechi Lopes, Mariana Matera Veras, Ivone Braga de Oliveira, Regiane Machado de Souza, Isac de Castro, Luzia Naôko Shinohara Furukawa, Paulo Hilário Nascimento Saldiva and Joel C. Heimann can be read at journals.plos.org/plosone/article?id=10.1371/journal.pone.0183314.