Open AccessEpididymis cell atlas in a patient with a sex development disorder and a novel NR5A1 gene mutation
Author(s) -
Jianwu Shi,
Yiwen Zhou,
Yufei Chen,
Mei Ye,
Feng Qiao,
Jiawei Tian,
Mengya Zhang,
Haocheng Lin,
Gangcai Xie,
Kin Lam Fok,
Hui Jiang,
Yang Liu,
Hao Chen
Publication year - 2023
Publication title -
asian journal of andrology/asian journal of andrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 74
eISSN - 1745-7262
pISSN - 1008-682X
DOI - 10.4103/aja202226
Subject(s) - epididymis , biology , missense mutation , nuclear receptor , mutation , medicine , endocrinology , microbiology and biotechnology , genetics , gene , transcription factor , sperm
This study aims to characterize the cell atlas of the epididymis derived from a 46,XY disorders of sex development (DSD) patient with a novel heterozygous mutation of the nuclear receptor subfamily 5 group A member 1 (NR5A1) gene. Next-generation sequencing found a heterozygous c.124C>G mutation in NR5A1 that resulted in a p.Q42E missense mutation in the conserved DNA-binding domain of NR5A1. The patient demonstrated feminization of external genitalia and Tanner stage 1 breast development. The surgical procedure revealed a morphologically normal epididymis and vas deferens but a dysplastic testis. Microfluidic-based single-cell RNA sequencing (scRNA-seq) analysis found that the fibroblast cells were significantly increased (approximately 46.5%), whereas the number of main epididymal epithelial cells (approximately 9.2%), such as principal cells and basal cells, was dramatically decreased. Bioinformatics analysis of cell-cell communications and gene regulatory networks at the single-cell level inferred that epididymal epithelial cell loss and fibroblast occupation are associated with the epithelial-to-mesenchymal transition (EMT) process. The present study provides a cell atlas of the epididymis of a patient with 46,XY DSD and serves as an important resource for understanding the pathophysiology of DSD.