Evidence for NR2F2/COUP-TFII involvement in human testis development
Issued Date
2024-12-01
Resource Type
eISSN
20452322
Scopus ID
2-s2.0-85200231391
Journal Title
Scientific Reports
Volume
14
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Scientific Reports Vol.14 No.1 (2024)
Suggested Citation
Wankanit S., Zidoune H., Bignon-Topalovic J., Schlick L., Houzelstein D., Fusée L., Boukri A., Nouri N., McElreavey K., Bashamboo A., Elzaiat M. Evidence for NR2F2/COUP-TFII involvement in human testis development. Scientific Reports Vol.14 No.1 (2024). doi:10.1038/s41598-024-68860-3 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/100403
Title
Evidence for NR2F2/COUP-TFII involvement in human testis development
Corresponding Author(s)
Other Contributor(s)
Abstract
NR2F2 encodes COUP-TFII, an orphan nuclear receptor required for the development of the steroidogenic lineages of the murine fetal testes and ovaries. Pathogenic variants in human NR2F2 are associated with testis formation in 46,XX individuals, however, the function of COUP-TFII in the human testis is unknown. We report a de novo heterozygous variant in NR2F2 (c.737G > A, p.Arg246His) in a 46,XY under-masculinized boy with primary hypogonadism. The variant, located within the ligand-binding domain, is predicted to be highly damaging. In vitro studies indicated that the mutation does not impact the stability or subcellular localization of the protein. NR5A1, a related nuclear receptor that is a key factor in gonad formation and function, is known to physically interact with COUP-TFII to regulate gene expression. The mutant protein did not affect the physical interaction with NR5A1. However, in-vitro assays demonstrated that the mutant protein significantly loses the inhibitory effect on NR5A1-mediated activation of both the LHB and INSL3 promoters. The data support a role for COUP-TFII in human testis formation. Although mutually antagonistic sets of genes are known to regulate testis and ovarian pathways, we extend the list of genes, that together with NR5A1 and WT1, are associated with both 46,XX and 46,XY DSD.