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

• DOI: 10.1038/s42003-025-07699-4
• Publication Date: 2025-02-16T14:57:32Z
• Authors: Jenifer P. Suntha...; Ignacio del Valle; Federica Buonocore; Sinead M. McGlack...; Tony Brooks; Olumide K. Ogunbiyi; Danielle Liptrot; Nathan Dunton; Gaganjit K. Madhan; Kate Metcalfe; Lydia Nel; Abigail R. Marshall; Miho Ishida; Neil J. Sebire; Gudrun E. Moore; Berta Crespo; Nita Solanky; Gerard S. Conway; John C. Achermann
• Keywords: Pseudoautosomal region; Monosomy; Genomic Imprinting; Dosage compensation

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