Early Gonadal Development and Sex Determination in Mammal

Xie, Yanshe; Wu, Changhua; Li, Zicong; Wu, Zhenfang; Hong, Linjun

doi:10.3390/ijms23147500

Cited by 4 publications

(4 citation statements)

References 256 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The interaction between somatic and germ cells and signaling from somatic cells is essential for the proliferation and differentiation of primordial germ cells. Furthermore, the female germ cells play a role in maintaining the ovary ( 23 ). Subsequently, the bipotential gonad differentiates into testis and ovary, respectively, through a sex-related genes antagonistic network.…”

Section: Clinical Presentationmentioning

confidence: 99%

Testicular differentiation in 46,XX DSD: an overview of genetic causes

Ferrari,

Silva,

Nishi

et al. 2024

Front. Endocrinol.

View full text Add to dashboard Cite

In mammals, the development of male or female gonads from fetal bipotential gonads depends on intricate genetic networks. Changes in dosage or temporal expression of sex-determining genes can lead to differences of gonadal development. Two rare conditions are associated with disruptions in ovarian determination, including 46,XX testicular differences in sex development (DSD), in which the 46,XX gonads differentiate into testes, and 46,XX ovotesticular DSD, characterized by the coexistence of ovarian and testicular tissue in the same individual. Several mechanisms have been identified that may contribute to the development of testicular tissue in XX gonads. This includes translocation of SRY to the X chromosome or an autosome. In the absence of SRY, other genes associated with testis development may be overexpressed or there may be a reduction in the activity of pro-ovarian/antitesticular factors. However, it is important to note that a significant number of patients with these DSD conditions have not yet recognized a genetic diagnosis. This finding suggests that there are additional genetic pathways or epigenetic mechanisms that have yet to be identified. The text will provide an overview of the current understanding of the genetic factors contributing to 46,XX DSD, specifically focusing on testicular and ovotesticular DSD conditions. It will summarize the existing knowledge regarding the genetic causes of these differences. Furthermore, it will explore the potential involvement of other factors, such as epigenetic mechanisms, in developing these conditions.

show abstract

Section: Clinical Presentationmentioning

confidence: 99%

Testicular differentiation in 46,XX DSD: an overview of genetic causes

Ferrari,

Silva,

Nishi

et al. 2024

Front. Endocrinol.

View full text Add to dashboard Cite

show abstract

“…In humans, the genital ridge, which gives rise to the testis or ovary, develops on the ventromedial surface of the mesonephros at four weeks of gestation ( Figure 1 ) [ 1 , 20 ]. Genes vital for this bipotential (or indifferent) gonad formation include WT1 , NR5A1 , CBX2 , LHX9 , EMX2 , and GATA4 [ 21 ].…”

Section: Testicular Development In Humansmentioning

confidence: 99%

“…Genes vital for this bipotential (or indifferent) gonad formation include WT1 , NR5A1 , CBX2 , LHX9 , EMX2 , and GATA4 [ 21 ]. At five weeks of gestation, bipotential primordial germ cells in the yolk sac migrate into the developing gonad [ 1 ], and coelomic epithelial cells within the genital ridge differentiate into supporting cell precursors (differentiating into Sertoli cells or granulosa cells) and steroidogenic cell precursors (differentiating into Leydig cells or theca cells) [ 20 ]. Male gonadal sex differentiation begins in somatic cells, first occurring in supporting cells and subsequently in steroidogenic cells.…”

Section: Testicular Development In Humansmentioning

confidence: 99%

“…At six weeks of gestation, SRY expression initiates the differentiation of supporting cell precursors into Sertoli cells [ 1 , 21 ]. This male sex differentiation of supporting cells involves SRY , SOX9 , NR5A1 , FGF9 , and PGD2 [ 1 , 20 , 21 ]. Sertoli cells secrete paracrine factors such as desert hedgehog and platelet-derived growth factor, which drive the differentiation of steroidogenic cell precursors into fetal Leydig cells [ 1 ].…”

Section: Testicular Development In Humansmentioning

confidence: 99%

See 1 more Smart Citation

Nuclear Receptor Gene Variants Underlying Disorders/Differences of Sex Development through Abnormal Testicular Development

Hattori

Fukami

2023

Biomolecules

View full text Add to dashboard Cite

Gonadal development is the first step in human reproduction. Aberrant gonadal development during the fetal period is a major cause of disorders/differences of sex development (DSD). To date, pathogenic variants of three nuclear receptor genes (NR5A1, NR0B1, and NR2F2) have been reported to cause DSD via atypical testicular development. In this review article, we describe the clinical significance of the NR5A1 variants as the cause of DSD and introduce novel findings from recent studies. NR5A1 variants are associated with 46,XY DSD and 46,XX testicular/ovotesticular DSD. Notably, both 46,XX DSD and 46,XY DSD caused by the NR5A1 variants show remarkable phenotypic variability, to which digenic/oligogenic inheritances potentially contribute. Additionally, we discuss the roles of NR0B1 and NR2F2 in the etiology of DSD. NR0B1 acts as an anti-testicular gene. Duplications containing NR0B1 result in 46,XY DSD, whereas deletions encompassing NR0B1 can underlie 46,XX testicular/ovotesticular DSD. NR2F2 has recently been reported as a causative gene for 46,XX testicular/ovotesticular DSD and possibly for 46,XY DSD, although the role of NR2F2 in gonadal development is unclear. The knowledge about these three nuclear receptors provides novel insights into the molecular networks involved in the gonadal development in human fetuses.

show abstract

COUP-TFII regulates early bipotential gonad signaling and commitment to ovarian progenitors

Ferreira

Kizys

Gama

et al. 2023

Preprint

View full text Add to dashboard Cite

The absence of expression of the Y-chromosome linked testis-determining gene SRY in early supporting gonadal cells (ESGC) of bipotential gonads leads to ovarian development. However, genetic variants in NR2F2/COUP-TFII represent a novel cause of SRY-negative 46,XX testicular/ovotesticular differences of sex development (T/OT-DSD). Thus, we hypothesized that COUP-TFII is part of the ovarian developmental network. We examined NR2F2/COUP-TFII expression and the genetic network under its regulation in human gonadal cells by analyzing single cell RNA-sequencing datasets of fetal gonads, differentiating induced pluripotent stem cells into bipotential gonad-like cells in vitro, and generating a NR2F2 knockout (KO) in the human granulosa-like cell line COV434. NR2F2 expression is highly upregulated during the bipotential gonad development, being detected in ESGCs. We identified that NR2F2 ablation in COV434 cells downregulated markers of ESGC and pre-granulosa cells, suggesting that COUP-TFII has a role in maintaining a multipotent state necessary for commitment to the ovarian development. We propose that impairment of COUP-TFII function may disrupt the transcriptional plasticity of ESGCs and instead drive them into commitment to the testicular pathway.

show abstract

Early Gonadal Development and Sex Determination in Mammal

Cited by 4 publications

References 256 publications

Testicular differentiation in 46,XX DSD: an overview of genetic causes

Testicular differentiation in 46,XX DSD: an overview of genetic causes

Nuclear Receptor Gene Variants Underlying Disorders/Differences of Sex Development through Abnormal Testicular Development

COUP-TFII regulates early bipotential gonad signaling and commitment to ovarian progenitors

Contact Info

Product

Resources

About