scholarly journals Environmentally Induced Epigenetic Transgenerational Inheritance of Altered Sertoli Cell Transcriptome and Epigenome: Molecular Etiology of Male Infertility

PLoS ONE ◽  
2013 ◽  
Vol 8 (3) ◽  
pp. e59922 ◽  
Author(s):  
Carlos Guerrero-Bosagna ◽  
Marina Savenkova ◽  
Md. Muksitul Haque ◽  
Eric Nilsson ◽  
Michael K. Skinner
Keyword(s):  
Male Infertility ◽  
Sertoli Cell ◽  
Transgenerational Inheritance ◽  
Molecular Etiology ◽  
Cell Transcriptome

scholarly journals Epigenetic transgenerational inheritance of testis pathology and Sertoli cell epimutations: generational origins of male infertility

2019 ◽  
Vol 5 (3) ◽  
Author(s):  
Ingrid Sadler-Riggleman ◽  
Rachel Klukovich ◽  
Eric Nilsson ◽  
Daniel Beck ◽  
Yeming Xie ◽  
...  
Keyword(s):  
Male Infertility ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Noncoding Rna ◽  
Cell Function ◽  
Sperm Concentration ◽  
Environmental Toxicants ◽  
Transgenerational Inheritance ◽  
Disease Etiology ◽  
General Decline

Abstract Male reproductive health has been in decline for decades with dropping sperm counts and increasing infertility, which has created a significant societal and economic burden. Between the 1970s and now, a general decline of over 50% in sperm concentration has been observed in the population. Environmental toxicant-induced epigenetic transgenerational inheritance has been shown to affect testis pathology and sperm count. Sertoli cells have an essential role in spermatogenesis by providing physical and nutritional support for developing germ cells. The current study was designed to further investigate the transgenerational epigenetic changes in the rat Sertoli cell epigenome and transcriptome that are associated with the onset of testis disease. Gestating female F0 generation rats were transiently exposed during the period of fetal gonadal sex determination to the environmental toxicants, such as dichlorodiphenyltrichloroethane (DDT) or vinclozolin. The F1 generation offspring were bred (i.e. intercross within the lineage) to produce the F2 generation grand-offspring that were then bred to produce the transgenerational F3 generation (i.e. great-grand-offspring) with no sibling or cousin breeding used. The focus of the current study was to investigate the transgenerational testis disease etiology, so F3 generation rats were utilized. The DNA and RNA were obtained from purified Sertoli cells isolated from postnatal 20-day-old male testis of F3 generation rats. Transgenerational alterations in DNA methylation, noncoding RNA, and gene expression were observed in the Sertoli cells from vinclozolin and DDT lineages when compared to the control (vehicle exposed) lineage. Genes associated with abnormal Sertoli cell function and testis pathology were identified, and the transgenerational impacts of vinclozolin and DDT were determined. Alterations in critical gene pathways, such as the pyruvate metabolism pathway, were identified. Observations suggest that ancestral exposures to environmental toxicants promote the epigenetic transgenerational inheritance of Sertoli cell epigenetic and transcriptome alterations that associate with testis abnormalities. These epigenetic alterations appear to be critical factors in the developmental and generational origins of testis pathologies and male infertility.

scholarly journals Disorders of Puberty: Endocrinology of the Pre-Pubertal Testis

2020 ◽  
Vol 9 (3) ◽  
pp. 780 ◽  
Author(s):  
Sandro La Vignera ◽  
Rossella Cannarella ◽  
Rosita A. Condorelli ◽  
Aldo E. Calogero
Keyword(s):  
Male Infertility ◽  
Sertoli Cell ◽  
Sperm Count ◽  
Sperm Concentration ◽  
Practical Approach ◽  
Testicular Function ◽  
Special Issue ◽  
Western Countries ◽  
Meta Regression

Male infertility is a widespread condition among western countries. Meta-regression data show that sperm concentration and total sperm count have halved in the last decades. The reasons of this decline are still unclear. The evaluation of testicular function in pre-pubertal children may be effective in the timely detection of Sertoli cell (SC) disfunction, which anticipates the diagnosis of male infertility. The aim of this Special Issue is to gather together in vitro evidence on SC physiology, causes of SC dysfunction, and to suggest a practical approach to be adopted in children.

scholarly journals Two distinct Sertoli cell states are regulated via germ cell crosstalk†

2021 ◽  
Author(s):  
Rachel L Gewiss ◽  
Nathan C Law ◽  
Aileen R Helsel ◽  
Eric A Shelden ◽  
Michael D Griswold
Keyword(s):  
Germ Cell ◽  
Sertoli Cell ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Seminiferous Tubule ◽  
Seminiferous Epithelium ◽  
Critical Component ◽  
Cell Transcriptome ◽  
Cell Crosstalk ◽  
Blood Testis Barrier

Abstract Sertoli cells are a critical component of the testis environment for their role in maintaining seminiferous tubule structure, establishing the blood-testis barrier, and nourishing maturing germ cells in a specialized niche. This study sought to uncover how Sertoli cells are regulated in the testis environment via germ cell crosstalk in the mouse. We found two major clusters of Sertoli cells as defined by their transcriptomes in Stages VII–VIII of the seminiferous epithelium and a cluster for all other stages. Additionally, we examined transcriptomes of germ cell-deficient testes and found that these existed in a state independent of either of the germ cell-sufficient clusters. Altogether, we highlight two main transcriptional states of Sertoli cells in an unperturbed testis environment, and a germ cell-deficient environment does not allow normal Sertoli cell transcriptome cycling and results in a state unique from either of those seen in Sertoli cells from a germ cell-sufficient environment.

scholarly journals Sertoli Cell-Only Syndrome: Behind the Genetic Scenes

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Katrien Stouffs ◽  
Alexander Gheldof ◽  
Herman Tournaye ◽  
Deborah Vandermaelen ◽  
Maryse Bonduelle ◽  
...  
Keyword(s):  
Male Infertility ◽  
Sertoli Cell ◽  
Germ Cells ◽  
Copy Number ◽  
Array Comparative Genomic Hybridization ◽  
Klinefelter Syndrome ◽  
Copy Number Variations ◽  
Comparative Genomic ◽  
Special Focus ◽  
Unselected Group

Sertoli cell-only syndrome is defined by the complete absence of germ cells in testicular tissues and always results in male infertility. The aetiology often remains unknown. In this paper, we have investigated possible causes of Sertoli cell-only syndrome with a special focus on genetic causes. Our results show that, for a large part of the patients (>23% in an unselected group), the sex chromosomes are involved. The majority of patients had a Klinefelter syndrome, followed by patients with Yq microdeletions. Array comparative genomic hybridization in a selected group of “idiopathic patients” showed no known infertility related copy number variations.

scholarly journals Novel Bi-Allelic Variants of FANCM Cause Sertoli Cell-Only Syndrome and Non-Obstructive Azoospermia

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuxiang Zhang ◽  
Peng Li ◽  
Nachuan Liu ◽  
Tao Jing ◽  
Zhiyong Ji ◽  
...  
Keyword(s):  
Male Infertility ◽  
Sertoli Cell ◽  
Severe Disease ◽  
Sporadic Case ◽  
Compound Heterozygous ◽  
Obstructive Azoospermia ◽  
Core Complex ◽  
Allelic Variants ◽  
Interstrand Crosslink ◽  
Compound Heterozygous Variants

Non-obstructive azoospermia (NOA) is the most severe disease in male infertility, but the genetic causes for the majority of NOA remain unknown. FANCM is a member of Fanconi Anemia (FA) core complex, whose defects are associated with cell hypersensitivity to DNA interstrand crosslink (ICL)-inducing agents. It was reported that variants in FANCM (MIM: 609644) might cause azoospermia or oligospermia. However, there is still a lack of evidence to explain the association between different FANCM variants and male infertility phenotypes. Herein, we identified compound heterozygous variants in FANCM in two NOA-affected brothers (c. 1778delG:p. R593Qfs*76 and c. 1663G > T:p. V555F), and a homozygous variant in FANCM (c. 1972C > T:p. R658X) in a sporadic case with NOA, respectively. H&E staining and immunohistochemistry showed Sertoli cell-only Syndrome (SCOS) in the three patients with NOA. Collectively, our study expands the knowledge of variants in FANCM, and provides a new insight to understand the genetic etiology of NOA.

Activin A Determines Steroid Levels and Composition in the Fetal Testis

Endocrinology ◽  
2020 ◽  
Vol 161 (7) ◽  
Author(s):  
Penny A F Whiley ◽  
Liza O’Donnell ◽  
Sarah C Moody ◽  
David J Handelsman ◽  
Julia C Young ◽  
...  
Keyword(s):  
Sertoli Cell ◽  
Sertoli Cells ◽  
Activin A ◽  
Rna Seq ◽  
Testis Development ◽  
Fetal Testis ◽  
Cell Transcriptome ◽  
First Time ◽  
Dose Dependent ◽  
Deficient Mice

Abstract Activin A promotes fetal mouse testis development, including driving Sertoli cell proliferation and cord morphogenesis, but its mechanisms of action are undefined. We performed ribonucleic acid sequencing (RNA-seq) on testicular somatic cells from fetal activin A-deficient mice (Inhba KO) and wildtype littermates at embryonic day (E) E13.5 and E15.5. Analysis of whole gonads provided validation, and cultures with a pathway inhibitor discerned acute from chronic effects of altered activin A bioactivity. Activin A deficiency predominantly affects the Sertoli cell transcriptome. New candidate targets include Minar1, Sel1l3, Vnn1, Sfrp4, Masp1, Nell1, Tthy1 and Prss12. Importantly, the testosterone (T) biosynthetic enzymes present in fetal Sertoli cells, Hsd17b1 and Hsd17b3, were identified as activin-responsive. Activin-deficient testes contained elevated androstenedione (A4), displayed an Inhba gene dose-dependent A4/T ratio, and contained 11-keto androgens. The remarkable accumulation of lipid droplets in both Sertoli and germ cells at E15.5 indicated impaired lipid metabolism in the absence of activin A. This demonstrated for the first time that activin A acts on Sertoli cells to determine local steroid production during fetal testis development. These outcomes reveal how compounds that perturb fetal steroidogenesis can function through cell-specific mechanisms and can indicate how altered activin levels in utero may impact testis development.

Male infertility in Sertoli cell‐only syndrome: An investigation of autosomal gene defects

2018 ◽  
Vol 26 (2) ◽  
pp. 292-298 ◽  
Author(s):  
Gulsah Koc ◽  
Abdullah A Ozdemir ◽  
Gozde Girgin ◽  
Cem Akbal ◽  
Deniz Kirac ◽  
...  
Keyword(s):  
Male Infertility ◽  
Sertoli Cell ◽  
Autosomal Gene ◽  
Gene Defects
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