Researchers from Cedars-Sinai and UCLA have uncovered important new findings that could help explain why health outcomes vary by sex. Their recent study, published in Biology of Sex Differences, reveals that the way genes are expressed in the placenta during early pregnancy may depend on the sex of the fetus. These differences in gene expression could influence a range of health outcomes, both during pregnancy and in later life.
The study highlights the rapid genetic changes the placenta undergoes in the first trimester, with some genes being expressed differently depending on whether the fetus is male or female. This research adds to the growing evidence that sex-based biological factors begin to play a role long before birth.
The research team, led by Dr. Margareta Pisarska, director of the Fertility and Reproductive Medicine Center at Cedars-Sinai, studied first trimester placental tissue from 56 women. These women had undergone chorionic villus sampling, a prenatal test for chromosomal abnormalities. The aim was to identify how certain signals activate or deactivate genes in relation to the sex of the fetus, and how these signals might influence pregnancy outcomes.
Among the genes that the researchers studied, 151 signals were identified as controlling gene activity. Notably, 18 genes were expressed differently depending on the sex of the fetus. For instance, one gene, ZNF300, was activated in females but not in males. This finding points to sex-based differences in gene regulation that the research team intends to explore further.
Some of these genes were located on the sex chromosomes (X and Y), which determine biological sex. However, several of the genes were located on chromosomes that both males and females share. This suggests that the sex of the fetus could influence broader genetic activity beyond the sex chromosomes.
The findings have significant implications for understanding how the sex of the fetus can affect both maternal and fetal health. Previous studies have shown that fetal sex can influence the mother’s risk of pregnancy-related conditions such as preeclampsia, gestational diabetes, hyperemesis gravidarum (severe morning sickness), and even miscarriage. This study sheds light on the biological mechanisms that could explain these associations.
“The fetus’s sex can impact a mother’s risk for certain conditions, and we are trying to understand how early gene expression might affect outcomes for both the mother and baby,” said Dr. Pisarska.
The researchers also found that sex differences in gene expression were more pronounced during the first trimester, as compared to later in pregnancy. In another study, published in Placenta, the team examined placental samples from both the first and third trimesters. Their findings suggest that early pregnancy is a crucial period for sex-based differences in gene activity, which may have long-lasting effects on health.
These sex-specific patterns in gene expression during early pregnancy could be linked to differences in adult health outcomes. For example, females are more prone to autoimmune diseases later in life compared to males, and these findings could provide new insights into why that is the case. Understanding how early gene expression contributes to such sex-based health disparities could open new avenues for preventive care.
According to Dr. Pisarska, “The expression of certain genes during early pregnancy may not only influence pregnancy outcomes but also contribute to sex differences in how certain diseases, like autoimmune disorders, develop in adulthood.”
The research team hopes to expand on these findings by studying how modifying gene expression in the early stages of pregnancy could potentially minimize health risks for both the mother and the child. This could lead to future interventions that target specific genes to prevent or reduce the risk of diseases linked to sex-based differences.
In conclusion, the study provides valuable insights into how early gene expression in the placenta could contribute to long-term sex differences in health. By better understanding these genetic mechanisms, researchers may be able to develop new strategies to improve pregnancy outcomes and reduce health disparities between males and females.
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