Intermediate filaments in the Sertoli cells of the ageing human testis

1997 ◽  
Vol 431 (2) ◽  
pp. 131-138 ◽  
Author(s):  
Mar�a P. de Miguel ◽  
Ferm�n R. Bethencourt ◽  
M. I. Arenas ◽  
Benito Fraile ◽  
R. Paniagua
1988 ◽  
Vol 178 (2) ◽  
pp. 129-136 ◽  
Author(s):  
Gerhard Aumüller ◽  
Manfred Steinbrück ◽  
Walter Krause ◽  
Hans-Joachim Wagner

2020 ◽  
Vol 9 (1) ◽  
pp. 266 ◽  
Author(s):  
Marsida Hutka ◽  
Lee B. Smith ◽  
Ellen Goossens ◽  
W. Hamish B. Wallace ◽  
Jan-Bernd Stukenborg ◽  
...  

The future fertility of prepubertal boys with cancer may be irreversibly compromised by chemotherapy and/or radiotherapy. Successful spermatogenesis has not been achieved following the xenotransplantation of prepubertal human testis tissue, which is likely due to the failure of somatic cell maturation and function. We used a validated xenograft model to identify the factors required for Leydig and Sertoli cell development and function in immature human testis. Importantly, we compared the maturation status of Sertoli cells in xenografts with that of human testis tissues (n = 9, 1 year-adult). Human fetal testis (n = 6; 14–21 gestational weeks) tissue, which models many aspects of prepubertal testicular development, was transplanted subcutaneously into castrated immunocompromised mice for ~12 months. The mice received exogenous human chorionic gonadotropin (hCG; 20IU, 3×/week). In xenografts exposed continuously to hCG, we demonstrate the maintenance of Leydig cell steroidogenesis, the acquisition of features of Sertoli cell maturation (androgen receptor, lumen development), and the formation of the blood–testis barrier (connexin 43), none of which were present prior to the transplantation or in xenografts in which hCG was withdrawn after 7 months. These studies provide evidence that hCG plays a role in Sertoli cell maturation, which is relevant for future investigations, helping them generate functional gametes from immature testis tissue for clinical application.


2000 ◽  
Vol 85 (9) ◽  
pp. 3453-3457 ◽  
Author(s):  
Emmanuele A. Jannini ◽  
Anna Crescenzi ◽  
Nadia Rucci ◽  
Emiliano Screponi ◽  
Eleonora Carosa ◽  
...  

Abstract We studied the spatiotemporal distribution of thyroid hormone nuclear receptors (TRs) α1 and α2 and β messenger RNA (mRNA) levels in normal human testicular tissue during development and in adulthood. Nonpathological specimens from five aborted fetuses (17 and 23 weeks of gestation, three and two cases, respectively) and from four patients undergoing orchiectomy (18 months old and 38-, 42-, and 52-yr-old, respectively) were analyzed by Northern blot, semiquantitative RT-PCR amplification using DNA sequences or specifically designed primers for the TR isoforms, and in situ hybridization. By using PCR amplification, we found that TRα1 and TRα2 are both expressed at different levels in fetal and adult testis. At all ages TRα2 is found at higher levels. Northern analysis showed hybridization signals corresponding to the expression of TRα2 and TRα1 in a ratio that increased from 2.6 at 17 weeks of gestation to 12.0 in adulthood. In fact, the expression of TRα1 dramatically decreased throughout development, being faintly detectable in the adult testis. Expression of TRβ was not detected at any age studied. This finding was further confirmed by PCR, which did not amplify TRβ either in fetal or in adult testis mRNAs. In situ hybridization studies showed the absence of TRβ and that TRα1 and TRα2 colocalized in Sertoli cells of prepubertal testis, whereas germ and interstitial cells appeared devoid of TR mRNA signals. From these results it can be concluded that the human testis exclusively expresses TRα, which is localized in Sertoli cells, TRβ being always undetectable. Fetal and prepubertal ages represent the period of maximal expression of TRα1 and TRα2. Theα 2/α1 ratio rises dramatically after development. These results confirm a critical window for the action of thyroid hormone in human testis, in the period of maximal expression of T3 binding isoform TRα1, and may account for the macroorchidism without virilization occurring when hyposecretion of thyroid hormones occurs before puberty.


Author(s):  
Zhengpin Wang ◽  
Xiaojiang Xu

In December 2019, a novel coronavirus (SARS-CoV-2) was identified in patients with pneumonia (called COVID-19) in Wuhan, Hubei Province, China. SARS-CoV-2 shares high sequence similarity and uses the same cell entry receptor, angiotensin-converting enzyme 2 (ACE2), as does severe acute respiratory syndrome coronavirus (SARS-CoV). Several studies have provided bioinformatic evidence of potential routes for SARS-CoV-2 infection in respiratory, cardiovascular, digestive and urinary systems. However, whether the reproductive system is a potential target of SARS-CoV-2 infection has not been determined. Here, we investigate the expression pattern of ACE2 in adult human testis at the level of single-cell transcriptomes. The results indicate that ACE2 is predominantly enriched in spermatogonia, Leydig and Sertoli cells. Gene ontology analyses indicate that GO categories associated with viral reproduction and transmission are highly enriched in ACE2-positive spermatogonia while male gamete generation related terms are down-regulated. Cell-cell junction and immunity related GO terms are increased in ACE2-positive Leydig and Sertoli cells, but mitochondria and reproduction related GO terms are decreased. These findings provide evidence that human testes are a potential target of SARS-CoV-2 infection which may have significant impact on our understanding of the pathophysiology of this rapidly spreading disease.


2009 ◽  
Vol 23 (5) ◽  
pp. 735-735
Author(s):  
Kahina Boukari ◽  
Geri Meduri ◽  
Sylvie Brailly-Tabard ◽  
Jean Guibourdenche ◽  
Maria Luisa Ciampi ◽  
...  

1979 ◽  
Vol 5 (3) ◽  
pp. 195-198 ◽  
Author(s):  
Massimo Re ◽  
Francesco Micali ◽  
Tommaso Racheli ◽  
Massimo Iannitelli

2007 ◽  
Vol 19 (1) ◽  
pp. 119
Author(s):  
L. Arregui ◽  
R. Rathi ◽  
W. Zeng ◽  
A. Honaramooz ◽  
M. Gomendio ◽  
...  

Testis tissue grafting presents an option for preservation of genetic material when sperm recovery is not possible. Grafting of testis tissue from sexually immature males to immunodeficient mice results in germ cell differentiation and production of fertilization-competent sperm from different mammalian species (Honaramooz et al. 2002 Nature 418, 778–781). However, the efficiency of testis tissue xenografting from adult donors has not been critically evaluated. Spermatogenesis was arrested at meiosis in grafts from mature horses (Rathi et al. 2006 Reproduction 131, 1091–1098) and hamsters (Schlatt et al. 2002 Reproduction 124, 339–346), and no germ cell differentiation occurred in xenografts of adult human testis tissue (Schlatt et al. 2006 Hum. Reprod. 21, 384–389). The objective of this study was to investigate survival and germ cell differentiation of testis xenografts from sexually mature donors of different species. Small fragments of testis tissue from 10 donor animals of 5 species were grafted under the back skin of immunodeficient, castrated male mice (n = 37, 2–6/donor). Donors were pig (8 months old), goat (18 months old and 4 years old) (n = 2), bull (3 years old), donkey (13 months old), and rhesus monkey (3, 6, 11, and 12 years old). At the time of grafting, donor tissue contained elongated spermatids, albeit to different degrees (>75% of seminiferous tubules in testis tissue from pig, goat, bull, and 6–12-year-old monkeys, and 33 or 66% of tubules in tissue from donkey or 3-year-old monkey, respectively). Grafts were recovered <12 weeks (n = 14 mice), 12–24 weeks (n = 16 mice), and >24 weeks (n = 7 mice) after grafting and classified histologically as completely degenerated (no tubules found), degenerated tubules (only hyalinized seminiferous tubules observed), or according to the most advanced type of germ cell present. Grafts from pig, goat, bull, and 6–12-year-old monkeys contained >60% degenerated tubules or were completely degenerated at all time points analyzed. In contrast, in grafts from the 3-year-old monkey, only 18% of tubules were degenerated, 14% contained Sertoli cells only, 64% contained meiotic, and 4% haploid germ cells at 24 weeks after grafting. Similarly, donkey testis grafts recovered 12–24 weeks after grafting contained <2% degenerated tubules, 46% of tubules had Sertoli cells only, 45% contained meiotic, and 7% haploid germ cells. These results show that survival and differentiation of germ cells in testis grafts from sexually mature mammalian donors is poor. However, better graft survival and maintenance of spermatogenesis occurred in donor tissue from donkey and 3-year-old monkey that were less mature at the time of grafting. Therefore, species and age-related differences appear to exist with regard to germ cell survival and differentiation in xenografts from adult donors. This work was supported by USDA/CSREES 03-35203-13486, NIH/NCRR 5-R01-RR17359-05, the Spanish Ministry of Education, and Science (BES-2004-4112).


Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2830
Author(s):  
Marsida Hutka ◽  
Prashant Kadam ◽  
Dorien Van Saen ◽  
Natalie Z. M. Homer ◽  
Jaime Onofre ◽  
...  

Survivors of childhood cancer are at risk for long-term treatment-induced health sequelae, including gonadotoxicity and iatrogenic infertility. At present, for prepubertal boys there are no viable clinical options to preserve future reproductive potential. We investigated the effect of a pubertal induction regimen with gonadotrophins on prepubertal human testis xenograft development. Human testis tissue was obtained from patients with cancer and non-malignant haematological disorders (n = 6; aged 1–14 years) who underwent testis tissue cryopreservation for fertility preservation. Fresh and frozen-thawed testis fragments were transplanted subcutaneously or intratesticularly into immunocompromised mice. Graft-bearing mice received injections of vehicle or exogenous gonadotrophins, human chorionic gonadotrophin (hCG, 20 IU), and follicle-stimulating hormone (FSH, 12.5 IU) three times a week for 12 weeks. The gross morphology of vehicle and gonadotrophin-exposed grafts was similar for both transplantation sites. Exposure of prepubertal human testis tissue xenografts to exogenous gonadotrophins resulted in limited endocrine function of grafts, as demonstrated by the occasional expression of the steroidogenic cholesterol side-chain cleavage enzyme (CYP11A1). Plasma testosterone concentrations (0.13 vs. 0.25 ng/mL; p = 0.594) and seminal vesicle weights (10.02 vs. 13.93 mg; p = 0.431) in gonadotrophin-exposed recipient mice were comparable to vehicle-exposed controls. Regardless of the transplantation site and treatment, initiation and maintenance of androgen receptor (AR) expression were observed in Sertoli cells, indicating commitment towards a more differentiated status. However, neither exogenous gonadotrophins (in castrated host mice) nor endogenous testosterone (in intact host mice) were sufficient to repress the expression of markers associated with immature Sertoli cells, such as anti-Müllerian hormone (AMH) and Ki67, or to induce the redistribution of junctional proteins (connexin 43, CX43; claudin 11, CLDN11) to areas adjacent to the basement membrane. Spermatogonia did not progress developmentally but remained the most advanced germ cell type in testis xenografts. Overall, these findings demonstrate that exogenous gonadotrophins promote partial activation and maturation of the somatic environment in prepubertal testis xenografts. However, alternative hormone regimens or additional factors for pubertal induction are required to complete the functional maturation of the spermatogonial stem cell (SSC) niche.


1986 ◽  
Vol 111 (1) ◽  
pp. 128-132 ◽  
Author(s):  
Outi Hovatta ◽  
I. Huhtaniemi ◽  
T. Wahlström

Abstract. The localisation of endogenous FSH and LH was studied in 4 inguinal adult human testes by the immunoperoxidase technique utilising antisera against the β-subunits of human FSH and LH. The content of available FSH and LH receptors was determined by radioreceptor assay. The Sertoli cells and about 10% of cells in the intersitium the Leydig cells, possibly the testicular macrophages, were similarly FSH-positive in cryptorchidism and control testes. The FSH receptor levels per testis were significantly lower in cryptorchidism than in control testes. Also the localisation of LH in Leydig cells in cryptorchidism was similar to the control testes, but the LH receptor level was significantly lower. These data bring further evidence for Leydig and Sertoli cell malfunction in the inguinal human testis.


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