Cedars-Sinai and UCLA investigators studied first-trimester placental tissue. They found that for some genes, the process that turns their information into a biological function may depend on the sex of the fetus.
The findings, published in Biology of Sex Differences, add to a growing body of research showing the placenta undergoes rapid genetic changes during the first trimester that may have effects lasting into adulthood.
“We know the fetus’ sex can impact a mother’s risk for conditions such as preeclampsia, hyperemesis, and gestational diabetes, as well as risk for miscarriage,” said Margareta Pisarska, MD, director of the Fertility and Reproductive Medicine Center at Cedars-Sinai and corresponding author of the study. “We are trying to understand what exactly happens during sex differentiation that may also affect outcomes for the mother and her baby.”
The investigators studied first-trimester placental tissue collected from 56 women who underwent chorionic villus sampling. This prenatal diagnostic test checks for chromosomal abnormalities and is typically offered to women who will be 35 or older when they give birth. The investigators sought to identify signals that turn genes on and off and how these signals lead to changes in gene expression.
Many of the genes they identified are on the X and Y chromosomes, which determine sex. (Women have two X chromosomes and men have one X and one Y.) However, the investigators also identified genes expressed on chromosomes that males and females share.
The investigators identified 151 signals that turn genes on and off. The signals affected 18 genes that were turned on or off depending on the sex of the fetus. One gene, for example, ZNF300, was turned on in females but not in males, an observation the investigative team intends to explore further.
In another recently published study, Pisarska and colleagues studied placental samples from women in their first and third trimesters and observed that sex differences in gene expression were more common in the first trimester.
“The expression of certain genes during early pregnancy may contribute to sex differences in the health and disease of adults,” Pisarska said. “Females, for example, are more likely than males to experience autoimmune diseases. We think gene expressions are markers that define not just pregnancy outcomes, but also tell us how sex differences in certain diseases are manifested.”
The investigators plan to study how modifying which genes get turned on or off might minimize disease in the mother, fetus, and eventual child and adult.
Newswise/VD