Abstract
The gonads are unique among the body’s organs in having a developmental choice: testis or ovary formation. Gonadal sex differentiation involves common progenitor cells that form either Sertoli and Leydig cells in the testis or granulosa and thecal cells in the ovary. Single-cell analysis is now shedding new light on how these cell lineages are specified and how they interact with the germline. Such studies are also providing new information on gonadal maturation, ageing and the somatic-germ cell niche. Furthermore, they have the potential to improve our understanding and diagnosis of Disorders/Differences of Sex Development (DSDs). DSDs occur when chromosomal, gonadal or anatomical sex are atypical. Despite major advances in recent years, most cases of DSD still cannot be explained at the molecular level. This presents a major pediatric concern. The emergence of single-cell genomics and transcriptomics now presents a novel avenue for DSD analysis, for both diagnosis and for understanding the molecular genetic etiology. Such -omics datasets have the potential to enhance our understanding of the cellular origins and pathogenesis of DSDs, as well as infertility and gonadal diseases such as cancer.
Highlights
Sex determination and sexual development in mammals can be divided into three broad stages
We can expect new variations and technologies emerging in the following years that will contribute to developing an accessible and cost-efficient single-cell sequencing method that can be applied to clinical diagnosis of Disorders/Differences of Sex Development (DSDs), gonadal cancers and infertility
Single-cell sequencing technologies have demonstrated a large potential in characterizing the different cell types present in the ovary and testis during normal development and disease
Summary
Sex determination and sexual development in mammals can be divided into three broad stages. The study of normal and abnormal gonadal development has moved into the so-called “-omics” era, whereby whole genome or whole transcriptome datasets have been analyzed. Such approaches are shedding new light on typical embryonic gonadal development, gonadal maturation, infertility, the somatic-germ cell niche, gonadal cancer and DSDs. DSD diagnosis has been advanced with the implementation of next-generation sequencing (NGS) methods such as whole exome and whole genome sequencing. Rather than using the whole gonad as the source tissue, -omics data can be obtained at single-cell resolution This technology allows genomic or transcriptomic changes within tissues to be assessed with granular detail, providing information of the different cell types present in normal and abnormal tissues. This review will focus on the application of emerging single-cell sequencing technologies to understand normal and atypical gonadal sex differentiation and function
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