ABSTRACT Monosomy X (45,X) is associated with Turner syndrome and pregnancy loss in humans, but the underlying mechanisms remain unclear. We therefore analyzed the transcriptomic landscape of clinically relevant human fetal 45,X tissues (including pancreas, liver, kidney, skin, placenta) with matched 46,XX and 46,XY control samples between 11-15 weeks post conception (n=78). Although most pseudoautosomal region 1 (PAR1) genes were lower in monosomy X tissues, we also found reduced expression of several key genes escaping X inactivation (e.g., KDM5C and KDM6A ), and potentially clinically important transcripts such as genes implicated in ascending aortic aneurysm. In contrast, higher expression of an autosomal, long non-coding RNA ( OVCH1-AS1 ) was seen in all 45,X tissues. In the placenta, lower expression of CSF2RA was demonstrated, likely contributing to immune dysregulation. Taken together, these findings provide novel insights into the biological consequences of a single X chromosome during early human development and potential insights in genetic mechanisms in Turner syndrome.

The transcriptomic landscape of monosomy X (45,X) during early human fetal and placental development