Development of the human fetal testis: Morphology and expression of cellular differentiation markers

Li, Yi; Overland, Maya; Derpinghaus, Amber; Aksel, Sena; Cao, Mei; Ladwig, Nicholas R; Cunha, Gerald R.; Baskin, Laurence S.

doi:10.1016/j.diff.2022.03.002

Cited by 11 publications

(3 citation statements)

References 59 publications

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“…PLAP is also expressed by human fetal GC with a decrease expression along GC differentiation. There are a few PLAP-positive GCs that can be retrieved from neonatal testis after birth, but these cells disappear after a few months (Li et al, 2023). In some cases, we could observed malignant neoplasms in testes after hGC transplantation (Figure 4E-F, Figure 5).…”

Section: Resultsmentioning

confidence: 99%

Evidence of the ability of endocrine disrupting compounds to induce testicular germ cell cancer in humans

Nicolas,

Moison,

Jampy

et al. 2023

Preprint

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Testicular cancer is an increasing burden in modern societies and the most common malignancy among young adult males. Environment contaminants, especially endocrine disrupting compounds (EDC), may play a significant role in the development of these cancers through epigenetic alterations occurring during fetal and neonatal development. As long-term studies in humans and suitable experimental models with the potential to develop testicular cancer are lacking, no causal link can be established between endocrine disruptor exposure and testicular cancer incidence. Therefore, we developed an experimental model that recapitulates the differentiation of germ cells from primordial germ cells (pluripotency) into spermatocytes (meiosis) by using xenografted human fetal testis combined with germ cell transplantation into adult testis compartments. Using this model, we demonstrate that long-term fetal exposure (until 12 weeks) to a mixture of Di-2-ethylhexylphthalate (DEHP) and Bisphenol A (BPA), two most prevalent plasticizers, could interfere with fetal germ cell differentiation, leading to carcinogenesis and seminomas. Transcriptome, methylome, and histological analyses reveal that BPA/DEHP exposure induced some significant hallmarks of germ cell tumors to occur: persistent pluripotent and proliferative germ cells, global hypomethylation of CpGs in germ cells, abnormal expression of meiotic markers and fibrotic signatures in fetal testis. Additionally, we found that EDC-exposed fetal germ cells were more likely to develop seminoma in a context that allows spermatogenesis to begin. This study proposes the first experimental evidence that EDC exposure can cause long-term, irreversible lesions in fetal germ cells, which then lead to testicular tumorigenesis in adults.

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Section: Resultsmentioning

confidence: 99%

Evidence of the ability of endocrine disrupting compounds to induce testicular germ cell cancer in humans

Nicolas,

Moison,

Jampy

et al. 2023

Preprint

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“…NR5A1 is primarily expressed in the adrenal glands, testes, ovaries, hypothalamus, pituitary gland, spleen, skin, and uterus [ 30 ]. In the testes, NR5A1 is expressed in Sertoli cells and Leydig cells throughout fetal development and postnatal life [ 23 , 24 ]. NR5A1 functions at various stages of testicular development.…”

Section: Nr5a1 (Nuclear Receptor Subfamily 5 Group a Member 1)mentioning

confidence: 99%

“…Dotted boxes indicate that it is unclear whether the gene is expressed. Gene expression data are based on those published previously [ 23 , 24 , 25 , 26 , 27 ]. Thin black arrows indicate the action of molecules, and thin red arrows depict cell migration.…”

Section: Figurementioning

confidence: 99%

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

Hattori

Fukami

2023

Biomolecules

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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.

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A model to study human ovotesticular syndrome

et al. 2023

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Development of the human fetal testis: Morphology and expression of cellular differentiation markers

Cited by 11 publications

References 59 publications

Evidence of the ability of endocrine disrupting compounds to induce testicular germ cell cancer in humans

Evidence of the ability of endocrine disrupting compounds to induce testicular germ cell cancer in humans

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

A model to study human ovotesticular syndrome

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