Scientists from the University of Adelaide’s Robinson Research Institute report that the placenta plays a key role in determining how male and female babies develop in different ways. They believe their work also sheds light on the underlying genetic and developmental reasons why male babies generally have worse outcomes than females, with significantly increased rates of pregnancy complications and poor health outcomes for males.

“Our research has found that there are undeniable genetic and physiological differences between boys and girls that extend beyond just the development of their sexual characteristics,” says Claire Roberts, Ph.D., leader of the fetal growth research priority for the Institute. “We've known for some time that girls are clearly winning in the battle for survival, with markedly better outcomes for female babies for preterm birth, stillbirth, neonatal death, and other complications after birth. Male babies generally grow faster and bigger than females. This occurs in both the animal and human worlds, but until now we haven't really understood how or why.”

The researchers, who published their study (“Integrative transcriptome meta-analysis reveals widespread sex-biased gene expression at the human fetal–maternal interface”) in Molecular Human Reproduction, investigated whether the type and pattern of genes being expressed by the placenta is different for boys and girls. They compared the genes expressed in 300 placenta samples and found that more than 140 genes were expressed differently across male and female samples.

“A majority of these genes (>60%) are autosomal, many of which are involved in high-level regulatory processes such as gene transcription, cell growth and proliferation, and hormonal function,” wrote the investigators. “Of particular interest, we detected higher female expression from all seven genes in the LHB-CGB cluster, which includes genes involved in placental development, the maintenance of pregnancy, and maternal immune tolerance of the conceptus. These results demonstrate that sex-biased gene expression in the normal human placenta occurs across the genome and includes genes that are central to growth, development, and the maintenance of pregnancy.”

“Our results suggest that there is a distinct sex bias in the regulation of genes in the human placenta,” says lead author and University of Adelaide doctoral student Sam Buckberry. “This suggests that girls are more likely to adopt a risk-averse strategy toward development and survival, and it goes some way to explaining the differences in male and female development in the womb.”
“These findings may be important to help guide future sex-specific therapeutics for pregnant women and for babies in the neonatal nursery,” adds Dr. Roberts.

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