CYP26B1 declines postnatally in Sertoli cells independently of androgen action in the mouse testis

Edelsztein, Nadia Yasmín; Kashimada, Kenichi; Schteingart, Helena Fedora; Rey, Rodolfo

doi:10.1002/mrd.23302

Cited by 6 publications

(4 citation statements)

References 53 publications

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“…One of the most significantly upregulated genes in KO Sertoli cells was Cyp26b1 which encodes an inhibitor of retinoic acid metabolism ( Supplementary Figures S5C , marked in Figure 5A with arrowhead). Cyp26b1 is the marker of immature Sertoli cells, and its transcriptional level declines postnatally ( Edelsztein et al, 2020 ). To assess whether FBXO38 deficiency results in a maturation defect in Sertoli cells, we profiled publicly available data from Sertoli cells isolated during the maturation period.…”

Section: Resultsmentioning

confidence: 99%

FBXO38 Ubiquitin Ligase Controls Sertoli Cell Maturation

Dibus

Zobalova

Monleon

et al. 2022

Front. Cell Dev. Biol.

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The ubiquitin ligase SCFFBXO38 controls centromeric chromatin by promoting the degradation of the ZXDB protein. To determine the importance of this pathway during development, Fbxo38-deficient mice were generated. The loss of FBXO38 resulted in growth retardation affecting several organs, including the male reproductive system. A detailed analysis of the mutant testes revealed pathological changes in the seminiferous tubules, accompanied by a significant decrease in sperm production and reduced fertility. In adult testes, FBXO38 was specifically expressed in Sertoli cells, a somatic population essential for spermatogenesis initiation and progression. Sertoli cells lacking FBXO38 exhibited stabilized ZXDB protein and upregulated centromeric chromatin. Furthermore, the gene expression profile revealed that the absence of FBXO38 led to a defect in Sertoli cell maturation, specifically characterized by dysregulation in genes controlling retinoic acid metabolism and intercellular communication. Consequently, we documented significant changes in their ability to initiate spermatogonial differentiation. In conclusion, we show that FBXO38 acts as a Sertoli cell maturation factor, affecting the Sertoli cell transcription program, centromere integrity, and, subsequently, the ability to control spermatogenesis.

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Section: Resultsmentioning

confidence: 99%

FBXO38 Ubiquitin Ligase Controls Sertoli Cell Maturation

Dibus

Zobalova

Monleon

et al. 2022

Front. Cell Dev. Biol.

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“…The expression of AMH declines significantly during pubertal development, and most Sertoli cell lines derived from adult testes do not express AMH 72 , 86 . SMAT1 cells maintain AMH expression, indicating that the basal transcriptional machinery for AMH is present 72 ; indeed, its validity for the study of AMH regulation has been already proven 23 – 25 , 29 , 33 , 87 . However, SMAT1 cells have lost the expression of all oestrogen receptors, as shown in the present work.…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanisms underlying AMH elevation in hyperoestrogenic states in males

Valeri

Lovaisa

Racine

et al. 2020

Sci Rep

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Anti-Müllerian hormone (AMH) is secreted by Sertoli cells of the testes from early fetal life until puberty, when it is downregulated by androgens. In conditions like complete androgen insensitivity syndrome (CAIS), AMH downregulation does not occur and AMH increases at puberty, due in part to follicle-stimulating hormone (FSH) effect. However, other conditions like Peutz-Jeghers syndrome (PJS), characterised by low FSH, also have increased AMH. Because both CAIS and PJS may present as hyperoestrogenic states, we tested the hypothesis that oestradiol (E2) upregulates AMH expression in peripubertal Sertoli cells and explored the molecular mechanisms potentially involved. The results showed that E2 is capable of inducing an upregulation of endogenous AMH and of the AMH promoter activity in the prepubertal Sertoli cell line SMAT1, signalling through ERα binding to a specific ERE sequence present on the hAMH promoter. A modest action was also mediated through the membrane oestrogen receptor GPER. Additionally, the existence of ERα expression in Sertoli cells in patients with CAIS was confirmed by immunohistochemistry. The evidence presented here provides biological plausibility to the hypothesis that testicular AMH production increases in clinical conditions in response to elevated oestrogen levels.

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“…Adult Leydig cells arise from multiple progenitors, such as fetal Leydig cells, peritubular myoid cells and vascular pericytes, during puberty [54,55]. Analysis of the expression of distinct markers of adult and fetal Leydig cells such as Hsd3b6 or Cyp26b1, respectively [56,57], in adult testes suggests a common dysfunction of adult and "fetal" Leydig cells. Moreover, the proliferation and differentiation of adult Leydig cells are regulated by multiple testicular and pituitary growth factors and hormones [58].…”

Section: Discussionmentioning

confidence: 99%

Unexpected Interacting Effects of Physical (Radiation) and Chemical (Bisphenol A) Treatments on Male Reproductive Functions in Mice

Wieckowski

Ranga

Moison

et al. 2021

IJMS

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For decades, numerous chemical pollutants have been described to interfere with endogenous hormone metabolism/signaling altering reproductive functions. Among these endocrine disrupting substances, Bisphenol A (BPA), a widely used compound, is known to negatively impact germ and somatic cells in the testis. Physical agents, such as ionizing radiation, were also described to perturb spermatogenesis. Despite the fact that we are constantly exposed to numerous environmental chemical and physical compounds, very few studies explore the impact of combined exposure to chemical and physical pollutants on reproductive health. The aim of this study was to describe the impact of fetal co-exposure to BPA and IR on testicular function in mice. We exposed pregnant mice to 10 µM BPA (corresponding to 0.5 mg/kg/day) in drinking water from 10.5 dpc until birth, and we irradiated mice with 0.2 Gy (γ-ray, RAD) at 12.5 days post-conception. Co-exposure to BPA and γ-ray induces DNA damage in fetal germ cells in an additive manner, leading to a long-lasting decrease in germ cell abundance. We also observed significant alteration of adult steroidogenesis by RAD exposure independently of the BPA exposure. This is illustrated by the downregulation of steroidogenic genes and the decrease of the number of adult Leydig cells. As a consequence, courtship behavior is modified, and male ultrasonic vocalizations associated with courtship decreased. In conclusion, this study provides evidence for the importance of broadening the concept of endocrine disruptors to include physical agents, leading to a reevaluation of risk management and regulatory decisions.

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CYP26B1 declines postnatally in Sertoli cells independently of androgen action in the mouse testis

Cited by 6 publications

References 53 publications

FBXO38 Ubiquitin Ligase Controls Sertoli Cell Maturation

FBXO38 Ubiquitin Ligase Controls Sertoli Cell Maturation

Molecular mechanisms underlying AMH elevation in hyperoestrogenic states in males

Unexpected Interacting Effects of Physical (Radiation) and Chemical (Bisphenol A) Treatments on Male Reproductive Functions in Mice

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