55 results match your criteria model sertoli-cell-only

Deficiency Causes Germ Cell Loss During Mouse Embryogenesis and Is Associated With Human Male Infertility.

Front Cell Dev Biol 2021 13;9:658966. Epub 2021 May 13.

Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.

Mutations affecting the germline can result in infertility or the generation of germ cell tumors (GCT), highlighting the need to identify and characterize the genes controlling germ cell development. The RNA-binding protein and E3 ubiquitin ligase TRIM71 is essential for embryogenesis, and its expression has been reported in GCT and adult mouse testes. To investigate the role of TRIM71 in mammalian germ cell embryonic development, we generated a germline-specific conditional knockout mouse (cKO) using the early primordial germ cell (PGC) marker as a Cre-recombinase driver. Read More

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Morphological and transcriptomic alterations in neonatal lamb testes following developmental exposure to low-level environmental chemical mixture.

Environ Toxicol Pharmacol 2021 Aug 5;86:103670. Epub 2021 May 5.

School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, UK. Electronic address:

Exposure to anthropogenic environmental chemical mixtures could be contributing to the decline in male reproductive health. This study used the biosolid treated pasture (BTP) sheep model to assess the effects of exposure to low-dose chemical mixtures. Maternal BTP exposure was associated with lower plasma testosterone concentrations, a greater proportion of Sertoli cell-only seminiferous tubules, and fewer gonocytes in the testes of neonatal offspring. Read More

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Trace the profile and function of circular RNAs in Sertoli cell only syndrome.

Genomics 2021 Jul 15;113(4):1845-1854. Epub 2021 Apr 15.

NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, Institute of Reproductive and Stem Cell Engineering, Central South University, Changsha, Hunan, China; Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, China. Electronic address:

Studies increasingly show the involvement of circular RNAs (circRNAs) in several diseases. This study aims to explore the circRNA expression pattern in the testicular tissues of patients with Sertoli only cell syndrome (SCOS) and their potential functions. High throughput circRNA microarray analysis indicated that 399 circRNAs were upregulated and 1195 were down-regulated (fold change >2, P < 0. Read More

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Establishment of gene knockout mice as a recipient model for spermatogonial stem cell transplantation.

Biol Open 2021 01 6;10(1). Epub 2021 Jan 6.

National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou 510642, China

Spermatogonial stem cell (SSC) transplantation is an alternative reproductive method to achieve conservation and production of elite animals in livestock production. Creating a recipient animal without endogenous germ cells is important for effective SSC transplantation. However, natural mutants with depletion of SSCs are difficult to obtain, and drug ablation of endogenous germ cells is arduous to perform for practical use. Read More

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January 2021

Over-expression of hsa_circ_0000116 in patients with non-obstructive azoospermia and its predictive value in testicular sperm retrieval.

Andrology 2020 11 28;8(6):1834-1843. Epub 2020 Aug 28.

Department of Pathology, Medical School, Xi'an Jiaotong University, Xi'an, China.

Background: Non-obstructive azoospermia (NOA), identified in approximately 10% of infertile males, is a multifactorial disease whose molecular mechanisms remain unknown.

Objectives: The aim of this study was to identify the role of hsa_circ_0000116 in NOA and illustrate its predictive value in testicular sperm retrieval.

Materials And Methods: The study included 78 individuals, 58 with NOA and 20 with obstructive azoospermia (OA). Read More

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November 2020

Phosphorylation of the Anaphase Promoting Complex activator FZR1/CDH1 is required for Meiosis II entry in mouse male germ cell.

Sci Rep 2020 06 22;10(1):10094. Epub 2020 Jun 22.

Department of Chromosome Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Kumamoto, 860-0811, Japan.

FZR1/CDH1 is an activator of Anaphase promoting complex/Cyclosome (APC/C), best known for its role as E3 ubiquitin ligase that drives the cell cycle. APC/C activity is regulated by CDK-mediated phosphorylation of FZR1 during mitotic cell cycle. Although the critical role of FZR1 phosphorylation has been shown mainly in yeast and in vitro cell culture studies, its biological significance in mammalian tissues in vivo remained elusive. Read More

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Testicular expression of TDRD1, TDRD5, TDRD9 and TDRD12 in azoospermia.

BMC Med Genet 2020 02 14;21(1):33. Epub 2020 Feb 14.

Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Background: Tudor domain-containing proteins (TDRDs) play a critical role in piRNA biogenesis and germ cell development. piRNAs, small regulatory RNAs, act by silencing of transposons during germline development and it has recently been shown in animal model studies that defects in TDRD genes can lead to sterility in males.

Methods: Here we evaluate gene and protein expression levels of four key TDRDs (TDRD1, TDRD5, TDRD9 and TDRD12) in testicular biopsy samples obtained from men with obstructive azoospermia (OA, n = 29), as controls, and various types of non-obstructive azoospermia containing hypospermatogenesis (HP, 28), maturation arrest (MA, n = 30), and Sertoli cell-only syndrome (SCOS, n = 32) as cases. Read More

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February 2020

Sequencing of a 'mouse azoospermia' gene panel in azoospermic men: identification of RNF212 and STAG3 mutations as novel genetic causes of meiotic arrest.

Hum Reprod 2019 06;34(6):978-988

Andrology Department, Fundació Puigvert, Universitat Autònoma de Barcelona, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), 08025 Barcelona, Catalonia, Spain.

Study Question: What is the diagnostic potential of next generation sequencing (NGS) based on a 'mouse azoospermia' gene panel in human non-obstructive azoospermia (NOA)?

Summary Answer: The diagnostic performance of sequencing a gene panel based on genes associated with mouse azoospermia was relatively successful in idiopathic NOA patients and allowed the discovery of two novel genes involved in NOA due to meiotic arrest.

What Is Known Already: NOA is a largely heterogeneous clinical entity, which includes different histological pictures. In a large proportion of NOA, the aetiology remains unknown (idiopathic NOA) and yet, unknown genetic factors are likely to play be involved. Read More

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Loss of connexin 43 in Sertoli cells provokes postnatal spermatogonial arrest, reduced germ cell numbers and impaired spermatogenesis.

Reprod Biol 2018 Dec 19;18(4):456-466. Epub 2018 Sep 19.

Institute of Anatomy, University of Veterinary Medicine Hannover, Bischofsholer Damm 15, 30173 Hannover, Germany. Electronic address:

For the reason that adult Sertoli cell specific connexin 43 knockout (SCCx43KO) mice show arrested spermatogenesis at spermatogonial level or Sertoli cell only tubules and significantly reduced germ cell (GC) numbers, the aims of the present study were (1) to characterize the remaining GC population and (2) to elucidate possible mechanisms of their fading. Apoptosis was analyzed in both, KO and wild type (WT) male littermates during postnatal development and in adulthood using TUNEL. Although GC numbers were significantly reduced in KO at 2 and 8 days postpartum (dpp) when compared to WT, no differences were found concerning apoptotic incidence between genotypes. Read More

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December 2018

Testicular histopathology, semen analysis and FSH, predictive value of sperm retrieval: supportive counseling in case of reoperation after testicular sperm extraction (TESE).

BMC Urol 2018 Jul 4;18(1):63. Epub 2018 Jul 4.

Centre for Reproductive Medicine, European Hospital, Rome, Italy.

Background: To provide indicators for the likelihood of sperm retrieval in patients undergoing testicular sperm extraction is a major issue in the management of male infertility by TESE. The aim of our study was to determine the impact of different parameters, including testicular histopathology, on sperm retrieval in case of reoperation in patients undergoing testicular sperm extraction.

Methods: We retrospectively analyzed 486 patients who underwent sperm extraction for intracytoplasmic sperm injection and testicular biopsy. Read More

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Cep55 overexpression causes male-specific sterility in mice by suppressing Foxo1 nuclear retention through sustained activation of PI3K/Akt signaling.

FASEB J 2018 09 17;32(9):4984-4999. Epub 2018 Apr 17.

Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute, Herston, Queensland, Australia.

Spermatogenesis is a dynamic process involving self-renewal and differentiation of spermatogonial stem cells, meiosis, and ultimately, the differentiation of haploid spermatids into sperm. Centrosomal protein 55 kDa (CEP55) is necessary for somatic cell abscission during cytokinesis. It facilitates equal segregation of cytoplasmic contents between daughter cells by recruiting endosomal sorting complex required for transport machinery (ESCRT) at the midbody. Read More

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September 2018

UXT is required for spermatogenesis in mice.

PLoS One 2018 12;13(4):e0195747. Epub 2018 Apr 12.

Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, United States of America.

Male mammals must simultaneously produce prodigious numbers of sperm and maintain an adequate reserve of stem cells to ensure continuous production of gametes throughout life. Failures in the mechanisms responsible for balancing germ cell differentiation and spermatogonial stem cell (SSC) self-renewal can result in infertility. We discovered a novel requirement for Ubiquitous Expressed Transcript (UXT) in spermatogenesis by developing the first knockout mouse model for this gene. Read More

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The protein phosphatase 1 regulator NIPP1 is essential for mammalian spermatogenesis.

Sci Rep 2017 10 17;7(1):13364. Epub 2017 Oct 17.

Laboratory of Biosignaling & Therapeutics, KU Leuven Department of Cellular and Molecular Medicine, University of Leuven, Leuven, Belgium.

NIPP1 is one of the major nuclear interactors of protein phosphatase PP1. The deletion of NIPP1 in mice is early embryonic lethal, which has precluded functional studies in adult tissues. Hence, we have generated an inducible NIPP1 knockout model using a tamoxifen-inducible Cre recombinase transgene. Read More

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October 2017

Factors influencing sperm retrieval following testicular sperm extraction in nonobstructive azoospermia patients.

Clin Exp Reprod Med 2017 Mar 31;44(1):22-27. Epub 2017 Mar 31.

Medical Genetics Laboratory, Al-Zahra University Hospital, Isfahan, Iran.

Objective: Azoospermia owing to testicular disorders is the most severe manifestation of male infertility. The main concern for patients with nonobstructive azoospermia (NOA) is the probability of successful sperm retrieval following testicular sperm extraction (TESE). Therefore, the goal of this study was to determine predictive factors correlated with sperm retrieval. Read More

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Progress in understanding the molecular functions of DDX3Y (DBY) in male germ cell development and maintenance.

Biosci Trends 2017 Mar 12;11(1):46-53. Epub 2017 Feb 12.

Laboratory of Biochemical Genetics of Animals, Institute of Molecular Genetics, Russian Academy of Sciences.

Human DDX3 paralogs are housed on the X chromosome (DDX3X) as well as in the non- recombining region Yq11 of the Y-chromosome (DDX3Y or DBY). A gene encoding RNA helicase DDX3Y is located in the AZoospermia Factor a (AZFa) region of the Y-chromosome and expressed only in male germ cells. Deletions encompassing the DDX3Y gene lead to azoospermia and cause Sertoli Cell-Only Syndrome (SCOS) in humans. Read More

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Irinotecan metabolite SN38 results in germ cell loss in the testis but not in the ovary of prepubertal mice.

Mol Hum Reprod 2016 11 28;22(11):745-755. Epub 2016 Jul 28.

Centre for Integrative Physiology, University of Edinburgh, Edinburgh EH8 9XD, UK

Study Question: Does the Irinotecan metabolite 7-ethyl-10-hydroxycamptothecan (SN38) damage the gonads of male and female prepubertal mice?

Summary Answer: The Irinotecan metabolite SN38 reduces germ cell numbers within the seminiferous tubules of mouse testes at concentrations that are relevant to cancer patients, while in contrast it has little if any effect on the female germ cell population.

What Is Known Already: Little is known about the role of the chemotherapeutic agent Irinotecan on female fertility, with only one article to date reporting menopausal symptoms in perimenopausal women treated with Irinotecan, while no data are available either on adult male fertility or on the impact of Irinotecan on the subsequent fertility of prepubertal cancer patients, female or male.

Study Design Size, Duration: Male and female gonads were obtained from postnatal day 5 C57BL/6 mice and exposed in vitro to a range of concentrations of the Irinotecan metabolite SN38: 0. Read More

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November 2016

Dynamin 2 is essential for mammalian spermatogenesis.

Sci Rep 2016 10 11;6:35084. Epub 2016 Oct 11.

School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia.

The dynamin family of proteins play important regulatory roles in membrane remodelling and endocytosis, especially within brain and neuronal tissues. In the context of reproduction, dynamin 1 (DNM1) and dynamin 2 (DNM2) have recently been shown to act as key mediators of sperm acrosome formation and function. However, little is known about the roles that these proteins play in the developing testicular germ cells. Read More

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October 2016

Testicular histology may predict the successful sperm retrieval in patients with non-obstructive azoospermia undergoing conventional TESE: a diagnostic accuracy study.

J Assist Reprod Genet 2017 Jan 21;34(1):149-154. Epub 2016 Sep 21.

Andro-Urology and IVF Unit, San Paolo Hospital, University of Milano, via Antonio Di Rudinì 8, 20142, Milan, Italy.

Purpose: The present study sought to determine the diagnostic accuracy of FSH level, testicular volume, and testicular histology in predicting the successful sperm retrieval (SSR) in a large cohort of patients with non-obstructive azoospermia undergoing conventional testicular sperm extraction (TESE).

Methods: We retrospectively evaluated 356 patients with non-obstructive azoospermia between June 2004 and July 2009. Binary logistic regression was used to evaluate the diagnostic accuracy of our predicting model, identifying sperm retrieval rate as binary dependent variable. Read More

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January 2017

Alteration of protein prenylation promotes spermatogonial differentiation and exhausts spermatogonial stem cells in newborn mice.

Sci Rep 2016 07 4;6:28917. Epub 2016 Jul 4.

MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center and the Medical School of Nanjing University, National Resource Center for Mutant Mice, Nanjing 210061, China.

Spermatogenesis in adulthood depends on the successful neonatal establishment of the spermatogonial stem cell (SSC) pool and gradual differentiation during puberty. The stage-dependent changes in protein prenylation in the seminiferous epithelium might be important during the first round of spermatogenesis before sexual maturation, but the mechanisms are unclear. We have previous found that altered prenylation in Sertoli cells induced spermatogonial apoptosis in the neonatal testis, resulting in adult infertility. Read More

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CRISPR/Cas9-mediated Dax1 knockout in the monkey recapitulates human AHC-HH.

Hum Mol Genet 2015 Dec 13;24(25):7255-64. Epub 2015 Oct 13.

MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center of Nanjing University, National Resource Center for Mutant Mice, Nanjing 210061, China, School of Life Science and Technology, ShanghaiTech University, 100 Haike Rd., Pudong New Area, Shanghai 201210, China and

Mutations in the DAX1 locus cause X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH), which manifest with primary adrenal insufficiency and incomplete or absent sexual maturation, respectively. The associated defects in spermatogenesis can range from spermatogenic arrest to Sertoli cell only syndrome. Conclusions from Dax1 knockout mouse models provide only limited insight into AHC/HH disease mechanisms, because mouse models exhibit more extensive abnormalities in testicular development, including disorganized and incompletely formed testis cords with decreased number of peritubular myoid cells and male-to-female sex reversal. Read More

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December 2015

DDX3Y gene rescue of a Y chromosome AZFa deletion restores germ cell formation and transcriptional programs.

Sci Rep 2015 Oct 12;5:15041. Epub 2015 Oct 12.

Institute for Stem Cell Biology and Regenerative Medicine &Department of Genetics, Stanford University, Stanford, CA, USA.

Deletions of the AZFa region (AZoospermia Factor-a) region of the human Y chromosome cause irreversible spermatogenic failure that presents clinically in men as Sertoli-cell only (SCO) pathology of the testis. Deletions of the AZFa region typically encompass two genes: DDX3Y and USP9Y. However, human genetic evidence indicates that SCO is most tightly linked to deletion of DDX3Y and that deletions/mutations of USP9Y can be transmitted from one generation to the next. Read More

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October 2015

Identification of Spermatogenically Active Regions in Rat Testes by Using Narrow-band Imaging System.

Urology 2015 Nov 8;86(5):929-35. Epub 2015 Sep 8.

Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.

Objective: To evaluate the feasibility of narrow-band imaging (NBI) system in microdissection testicular sperm extraction (micro-TESE).

Materials And Methods: Firstly, we investigated angiogenic potential in human testicular specimens obtained from 48 patients who underwent micro-TESE. We then created a testicular injury model in rats with a single topical injection of cisplatin into the testes, and the testes were observed with and without NBI. Read More

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November 2015

Abnormal Accumulation of Collagen Type I Due to the Loss of Discoidin Domain Receptor 2 (Ddr2) Promotes Testicular Interstitial Dysfunction.

PLoS One 2015 9;10(7):e0131947. Epub 2015 Jul 9.

Department of Human Anatomy, Histology and Embryology, Fourth Military Medical University, Xi'an 710032, China.

Background: Loss of functional allele for discoidin domain receptor 2 (Ddr2) results in impaired Leydig cell response to luteinizing hormone (LH), low testosterone production and arrested spermatogenesis in older male Ddr2slie/slie mice. However, the underlying mechanism responsible for this phenotype remains unknown. Herein, we reported for the first time that the deregulated expression of Ddr2 cognate ligand, namely collagen type I (COL1), may account for the disruption of the testicular steroidogenesis in Ddr2slie/slie mutant testes. Read More

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Etiology of azoospermia in a military population.

J Urol 2015 Apr 16;193(4):1318-21. Epub 2014 Oct 16.

Department of Urology, Naval Medical Center San Diego, San Diego, California; Department of Urology, Naval Medical Center Portsmouth (RCW), Portsmouth, Virginia. Electronic address:

Purpose: Male infertility is commonly seen at urology clinics and 10% to 20% of infertile males are found to be azoospermic. Azoospermia is classically categorized as nonobstructive or obstructive. This classification tailors the evaluation, diagnosis and proper treatment. Read More

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Intratesticular testosterone is increased in men with Klinefelter syndrome and may not be released into the bloodstream owing to altered testicular vascularization– a preliminary report.

Andrology 2014 Mar;2(2):275-81

Klinefelter syndrome (KS, 47,XXY) is associated with low serum testosterone (T), long thought to arise from disturbed steroidogenesis in Leydig cells. However, intratesticular testosterone (ITT) concentrations were recently found to be normal in a KS mouse model(41,XXY*). So far, nothing was known about ITT concentrations in human patients with KS. Read More

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Identification of spermatogenesis in a rat sertoli-cell only model using Raman spectroscopy: a feasibility study.

J Urol 2014 Aug 8;192(2):607-12. Epub 2014 Feb 8.

Department of Urology, New York Presbyterian Hospital, Weill Cornell Medical College, New York, New York. Electronic address:

Purpose: We determined whether Raman spectroscopy could identify spermatogenesis in a Sertoli-cell only rat model.

Materials And Methods: A partial Sertoli-cell only model was created using a testicular hypothermia-ischemia technique. Bilateral testis biopsy was performed in 4 rats. Read More

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Altered protein prenylation in Sertoli cells is associated with adult infertility resulting from childhood mumps infection.

J Exp Med 2013 Jul 1;210(8):1559-74. Epub 2013 Jul 1.

MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center and Jiangsu Key Laboratory of Molecular Medicine of the School of Medicine, Nanjing University, National Resource Center for Mutant Mice, Nanjing 210061, China.

Mumps commonly affects children 5-9 yr of age, and can lead to permanent adult sterility in certain cases. However, the etiology of this long-term effect remains unclear. Mumps infection results in progressive degeneration of the seminiferous epithelium and, occasionally, Sertoli cell-only syndrome. Read More

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[Establishing a mouse model of Sertoli-cell-only syndrome by administration of busulfan].

Zhonghua Nan Ke Xue 2013 Apr;19(4):300-5

Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, China.

Objective: To establish a stable and reliable model of Sertoli-cell-only syndrome in mice.

Methods: We randomly divided 60 NIH mice into two groups of equal number to receive intraperitoneal injection of busulfan (30 mg/kg) and 30 or 60 minutes of testis cooling. At 2, 4 and 8 weeks after treatment, we recorded the survival rate of the mice, weight of the testis and Johnsen scores, and conducted quantitative analysis on the degrees of spermatogenetic failure. Read More

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Distribution of Zonula Occludens-1 and Occludin and alterations of testicular morphology after in utero radiation and postnatal hyperthermia in rats.

Int J Exp Pathol 2012 Dec;93(6):438-49

Department of Histology and Embryology, School of Medicine, Marmara University, Istanbul, Turkey.

In utero irradiation (IR) and postnatal hyperthermia (HT) exposure cause infertility by decreasing spermatogenic colony growth and the number of sperm in rats. Four groups were used: (i) Control group, (ii) HT group (rats exposed to hyperthermia on the 10th postnatal day), (iii) IR group (rats exposed to IR on the 17th gestational day) and (iv) IR + HT group. Three and six months after the procedures testes were examined by light and electron microscopy. Read More

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December 2012

Autologous ectopic grafting of cryopreserved testicular tissue preserves the fertility of prepubescent monkeys that receive sterilizing cytotoxic therapy.

Cancer Res 2012 Oct 17;72(20):5174-8. Epub 2012 Aug 17.

Department of Cell Biology and Physiology, Center for Research in Reproductive Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Boys faced with future sterility as a result of the need of a sterilizing cancer therapy might avoid this fate by engraftment of cryopreserved immature testicular tissue after therapy is completed. Efforts to address this important survivorship issue have been encouraged by reports of the long-term survival and proliferation of human spermatogonia after xenotransplant of cryopreserved immature testicular tissue into immunocompromised murine hosts. However, spermatogenic arrest at the pachytene spermatocyte stage that occurs in this situation has been associated with a failure in sperm production. Read More

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October 2012