A team of researchers led by the University of Helsinki and Helsinki University Hospital published a study that reveals mechanisms of preeclampsia. The findings—reported on EBiomedicine—also show that “there is a gene directly influencing the balance of boys and girls born,” says lead author Satu Wedenoja.
Their sample population included 1.79 million births from the Finnish Birth Registry, a group of stillborn babies, and a national preeclampsia cohort. Specifically, they studied placental mRNA expression of 136 genes by sequencing HLA-G and interferon-alpha protein expression by immunohistochemistry. Initial results showed that girls are more likely to be born from preeclamptic pregnancy than boys, especially among those delivered preterm.
The data gathered links regulatory HLA-G to the offspring sex and pregnancy complications through balance selection mechanisms: negative frequency-dependent selection and heterozygote advantage. Consistently, they observed sex-linked downregulation of HLA-G, downregulation of HLA-G receptors as well as an increased interferon signaling, suggesting that fetal HLA-G modulates preeclampsia, and human birth sex ratio.
"The results show that natural selection works through the fetal HLA-G gene influencing the pregnancy outcome and its complications. The results further strengthen earlier findings of the vulnerability of boys to mother's inflammation, late miscarriages, and preeclampsia," says Wedenoja. Their findings propose that treatment and widely used medication for autoimmune disorders could be tested for preeclampsia prevention or treatment.