Gene expression in the placenta is different for male and female fetuses during the first trimester.
Researchers at Cedars-Sinai, California, and the University of California, Los Angeles, have discovered that the expression of certain genes in the placenta during the first trimester (from conception to 12 weeks) may depend on the sex of the fetus.
'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 Dr Margareta Pisarska, director of the Fertility and Reproductive Medicine Centre at Cedars-Sinai and corresponding author of the study published in Biology of Sex Differences. 'We are trying to understand what exactly happens during sex differentiation that may also affect outcomes for the mother and her baby.'
Using placental tissue samples collected from 56 women undergoing chorionic villus sampling (CVS), the scientists aimed to identify first trimester human placenta DNA methylation differences due to the sex of the fetus. DNA methylation is an epigenetic mechanism that cells use to control gene expression. Out of 743,461 sites analysed, they identified 151 sites that were affected by the sex of the fetus, encompassing 11 regions across the genome, and which changed how a gene was expressed.
To confirm their findings, the scientists also sequenced placental RNA from the same tissue samples and compared the results with the DNA methylation differences observed. Most of the genes affected were on the sex chromosomes – an X chromosome and a Y chromosome in males, and two X chromosomes in females. However, 18 genes affected were on autosomes – all chromosomes that are not sex chromosomes, and which males and females share. These genes showed both significant DNA methylation differences and gene expression changes.
DNA methylation typically reduces the expression of a gene. This study in particular discovered that the transcription factor ZNF300 had higher DNA methylation in males and thus reduced gene expression. In turn, ZNF300 was not hypermethylated in females and thus higher gene expression was observed.
The authors hypothesise that the expression of certain genes during early pregnancy may contribute to the health and disease of the mother, fetus and eventual child and adult.
'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.' Dr Pisarska said.
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