Establishment and validation of an approach allowing unequivocal fetal sex determination based on placental sex-specific genes

The use of human placenta as a matrix for the prediction of the baby's sex has been recently documented, but evaluation methods for placental sex-determining genes allowing reliable sex prediction are still lacking. We compared the accuracy of the retrospective prediction of the baby's sex using placental mRNA expression of RPS4Y1, DDX3Y, and XIST analyzed by an already reported method and a newly developed evaluation approach. Full concordance between the predicted and the actual baby sex was only obtained when analyzing placental RPS4Y1 expression with the newly proposed method, which was found to be robust and reliable. •Reliable fetal sex determination requires a carefully calibrated method.•No “black and white”-like expression of RPS4Y1, DDX3Y and XIST in placentas.•RPS4Y1 appears as a robust sex-determining gene in human placental samples.