scholarly journals Maturation of Testicular Tissue from Infant Monkeys after Xenografting into Mice

Endocrinology ◽  
2008 ◽  
Vol 149 (10) ◽  
pp. 5288-5296 ◽  
Author(s):  
Rahul Rathi ◽  
Wenxian Zeng ◽  
Susan Megee ◽  
Alan Conley ◽  
Stuart Meyers ◽  
...  
Keyword(s):  
Germ Cell ◽  
Somatic Cell ◽  
Sertoli Cell ◽  
Rhesus Monkeys ◽  
Testicular Tissue ◽  
Cell Maturation ◽  
Nuclear Antigen ◽  
Donor Age ◽  
Germ Cell Differentiation ◽  
Testis Tissue

In juvenile monkeys, precocious puberty can be induced by administration of gonadotropins resulting in testicular somatic cell maturation and germ cell differentiation. It is, however, unknown whether testicular maturation can also be induced in younger monkeys. Here we used testis tissue xenografting to investigate whether infant monkey testis tissue will undergo somatic cell maturation and/or spermatogenesis in response to endogenous adult mouse gonadotropins or exogenous gonadotropins. Testicular tissue pieces from 3- and 6-month-old rhesus monkeys were grafted to immunodeficient, castrated mice. Recipient mice were either left untreated or treated with pregnant mare serum gonadotropin and/or human chorionic gonadotropin twice weekly and were killed 28 weeks after grafting. Testicular maturation in grafted tissue was assessed based on morphology and the most advanced germ cell type present and by immunohistochemistry for expression of proliferating cell nuclear antigen, Mullerian-inhibiting substance, and androgen receptor. Testis grafts, irrespective of donor age or treatment, contained fewer germ cells than donor tissue. Grafts from 6-month-old donors showed tubular expansion with increased seminiferous tubule diameter and lumen formation, whereas those harvested from gonadotropin-treated mice contained elongated spermatids. Grafts from 3-month-old donors recovered from gonadotropin-treated mice contained pachytene spermatocytes, whereas those recovered from untreated mice showed only slight tubular expansion. Immunohistochemistry revealed that exposure to exogenous gonadotropins supported Sertoli cell maturation, irrespective of donor age. These results indicate that sustained gonadotropin stimulation of immature (<12 months old) monkey testis supports Sertoli cell maturation, thereby terminating the unresponsive phase of the germinal epithelium and allowing complete spermatogenesis in testis tissue from infant rhesus monkeys.

The initial maturation status of marmoset testicular tissues has an impact on germ cell maintenance and somatic cell response in tissue fragment culture

2020 ◽  
Vol 26 (6) ◽  
pp. 374-388 ◽  
Author(s):  
L Heckmann ◽  
D Langenstroth-Röwer ◽  
J Wistuba ◽  
J M D Portela ◽  
A M M van Pelt ◽  
...  
Keyword(s):  
Germ Cell ◽  
Somatic Cell ◽  
Sertoli Cell ◽  
Cell Response ◽  
Testicular Tissue ◽  
Cell Maturation ◽  
Differentiation Potential ◽  
Fragment Culture ◽  
Cell Maintenance

Abstract Successful in vitro spermatogenesis was reported using immature mouse testicular tissues in a fragment culture approach, raising hopes that this method could also be applied for fertility preservation in humans. Although maintaining immature human testicular tissue fragments in culture is feasible for an extended period, it remains unknown whether germ cell survival and the somatic cell response depend on the differentiation status of tissue. Employing the marmoset monkey (Callithrix jacchus), we aimed to assess whether the maturation status of prepubertal and peri-/pubertal testicular tissues influence the outcome of testis fragment culture. Testicular tissue fragments from 4- and 8-month-old (n = 3, each) marmosets were cultured and evaluated after 0, 7, 14, 28 and 42 days. Immunohistochemistry was performed for identification and quantification of germ cells (melanoma-associated antigen 4) and Sertoli cell maturation status (anti-Müllerian hormone: AMH). During testis fragment culture, spermatogonial numbers were significantly reduced (P < 0.05) in the 4- but not 8-month-old monkeys, at Day 0 versus Day 42 of culture. Moreover, while Sertoli cells from 4-month-old monkeys maintained an immature phenotype (i.e. AMH expression) during culture, AMH expression was regained in two of the 8-month-old monkeys. Interestingly, progression of differentiation to later meiotic stage was solely observed in one 8-month-old marmoset, which was at an intermediate state regarding germ cell content, with gonocytes as well as spermatocytes present, as well as Sertoli cell maturation status. Although species-specific differences might influence the outcome of testis fragment experiments in vitro, our study demonstrated that the developmental status of the testicular tissues needs to be considered as it seems to be decisive for germ cell maintenance, somatic cell response and possibly the differentiation potential.

318 EFFECT OF 6-N-PROPYL-2-THIOURACIL-INDUCED HYPOTHYROIDISM IN THE HOST MOUSE ON THE DEVELOPMENT OF BOVINE TESTIS XENOGRAFTS

2010 ◽  
Vol 22 (1) ◽  
pp. 315
Author(s):  
J. R. Rodriguez-Sosa ◽  
G. M. J. Costa ◽  
R. Rathi ◽  
L. R. França ◽  
I. Dobrinski
Keyword(s):  
Cell Differentiation ◽  
Germ Cell ◽  
Sertoli Cell ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Cell Maturation ◽  
Germ Cell Differentiation ◽  
Host Mouse ◽  
Thyroid Hormone Levels ◽  
Collection Time

In rodents, thyroid hormones inhibit Sertoli cell proliferation, promote Sertoli cell differentiation, and accelerate lumen formation in the seminiferous tubules. Conversely, transient hypothyroidism prolongs Sertoli cell proliferation, leading to increased Sertoli cell number and testicular size. In order to evaluate whether 6-N-propyl-2-thiouracil (PTU)-induced hypothyroidism in the host mouse would affect seminiferous tubule development and germ cell differentiation, and subsequently increase spermatogenesis in bovine testis xenografts, fragments (∼1 mm3) of testes from 1-wk-old Holstein calves (n = 6) were transplanted ectopically to castrated immunodeficient male mice (n = 6/donor). Mice (n = 3/donor) were treated with 0.1% (w/v) PTU in drinking water for 4 weeks or left as control. At 5 and 7 months after grafting, grafts were analyzed by morphometry and immunohistochemistry for expression of protein gene product 9.5 (PGP 9.5) as a germ cell marker, and Mullerian-inhibiting substance (MIS) and androgen receptor (AR) to assess Sertoli cell maturation. For each variable, averages of each group were compared at each collection point by t-test PTU treatment to the drinking water for 1 month suppressed thyroid hormone levels (T4) in host mice without negative systemic effects (0.3 ± 0.2 v. 4 ± 0.3 μg dL-1 at 4 weeks in treated v. control mice, respectively, P < 0.05). Spermatogenesis in recovered grafts was arrested at meiosis regardless of treatment and collection time. Graft weight was lower in treated mice than in controls (21 ± 4 v. 42 ± 5 and 24 ± 9 v. 51 ± 5 mg, at 5 and 7 months, respectively, P < 0.05). Volume density of the tubular and intertubular compartments, and seminiferous epithelium, was not affected by treatment (P > 0.05); however, treatment reduced lumen density compared to controls (9 ± 2 v. 19 ± 3 and 12 ± 1 v. 24 ± 4%) and tubular diameter (121 ± 3 v. 140 ± 7 and 144 ± 2v. 170 ± 2 (im, at 5 and 7 months, respectively (P < 0.05). Tubule length per milligram was not different at 5 months between control and treated groups (P > 0.05) but was increased at 7 months in the treated grafts (50 ± 1 v. 30 ± 1 cm, P < 0.05). Number of Sertoli cells per milligram was not affected by treatment (P > 0.05). However, Sertoli cell volume was increased in controls (440 ± 19 v. 341 ± 14 and 504 ± 6 v. 388 ± 18 μm3, at 5 and 7 months, respectively, P < 0.05). The number of germ cells per 100 Sertoli cells was not different between groups at any collection time (P > 0.05). Sertoli cells showed variable MIS expression and lack of or weak AR expression regardless of treatment and collection time, indicating an immature phenotype. In conclusion, suppression of thyroid hormone levels in host mice affects seminiferous tubule development in bovine testis xenografts, demonstrating that endocrine manipulation of the mouse host will affect xenografts in a predictable manner. However, treatment did not affect number and differentiation of germ cells. Rather, incomplete Sertoli cell maturation appears to lead to incomplete germ cell differentiation in bovine testis xenografts. Supported by USDA (2007-35203-18213).

scholarly journals Changes in Expression of Specific mRNA Transcripts after Single- or Re-Irradiation in Mouse Testes

Genes ◽  
2022 ◽  
Vol 13 (1) ◽  
pp. 151
Author(s):  
Kenta Nagahori ◽  
Ning Qu ◽  
Miyuki Kuramasu ◽  
Yuki Ogawa ◽  
Daisuke Kiyoshima ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Germ Cell ◽  
Sertoli Cell ◽  
Alkylating Agents ◽  
Mrna Species ◽  
Germ Cell Differentiation ◽  
Targeted Treatments ◽  
Mrna Transcripts ◽  
Specific Mrna

Alkylating agents and irradiation induce testicular damage, which results in prolonged azoospermia. Even very low doses of radiation can significantly impair testis function. However, re-irradiation is an effective strategy for locally targeted treatments and the pain response and has seen important advances in the field of radiation oncology. At present, little is known about the relationship between the harmful effects and accumulated dose of irradiation derived from continuous low-dose radiation exposure. In this study, we examined the levels of mRNA transcripts encoding markers of 13 markers of germ cell differentiation and 28 Sertoli cell-specific products in single- and re-irradiated mice. Our results demonstrated that re-irradiation induced significantly decreased testicular weights with a significant decrease in germ cell differentiation mRNA species (Spo11, Tnp1, Gfra1, Oct4, Sycp3, Ddx4, Boll, Crem, Prm1, and Acrosin). In the 13 Sertoli cell-specific mRNA species decreased upon irradiation, six mRNA species (Claudin-11,Espn, Fshr, GATA1, Inhbb, and Wt1) showed significant differences between single- and re-irradiation. At the same time, different decreases in Sertoli cell-specific mRNA species were found in single-irradiation (Aqp8, Clu, Cst12, and Wnt5a) and re-irradiation (Tjp1, occludin,ZO-1, and ZO-2) mice. These results indicate that long-term aspermatogenesis may differ after single- and re-irradiated treatment.

scholarly journals Smad3 Dosage Determines Androgen Responsiveness and Sets the Pace of Postnatal Testis Development

Endocrinology ◽  
2011 ◽  
Vol 152 (5) ◽  
pp. 2076-2089 ◽  
Author(s):  
Catherine Itman ◽  
Chin Wong ◽  
Briony Hunyadi ◽  
Matthias Ernst ◽  
David A. Jans ◽  
...  
Keyword(s):  
Germ Cell ◽  
Sertoli Cell ◽  
Pubertal Development ◽  
Cell Development ◽  
Cell Maturation ◽  
Developmentally Regulated ◽  
Testis Development ◽  
Essentially Normal ◽  
Endocrine Factors ◽  
Immature Cells

The establishment and maturation of the testicular Sertoli cell population underpins adult male fertility. These events are influenced by hormones and endocrine factors, including FSH, testosterone and activin. Activin A has developmentally regulated effects on Sertoli cells, enhancing proliferation of immature cells and later promoting postmitotic maturation. These differential responses correlate with altered mothers against decapentaplegic (SMAD)-2/3 signaling: immature cells signal via SMAD3, whereas postmitotic cells use both SMAD2 and SMAD3. This study examined the contribution of SMAD3 to postnatal mouse testis development. We show that SMAD3 production and subcellular localization are highly regulated and, through histological and molecular analyses, identify effects of altered Smad3 dosage on Sertoli and germ cell development. Smad3+/− and Smad3−/− mice had smaller testes at 7 d postpartum, but this was not sustained into adulthood. Juvenile and adult serum FSH levels were unaffected by genotype. Smad3-null mice displayed delayed Sertoli cell maturation and had reduced expression of androgen receptor (AR), androgen-regulated transcripts, and Smad2, whereas germ cell and Leydig cell development were essentially normal. This contrasted remarkably with advanced Sertoli and germ cell maturation and increased expression of AR and androgen-regulated transcripts in Smad3+/− mice. In addition, SMAD3 was down-regulated during testis development and testosterone up-regulated Smad2, but not Smad3, in the TM4 Sertoli cell line. Collectively these data reveal that appropriate SMAD3-mediated signaling drives normal Sertoli cell proliferation, androgen responsiveness, and maturation and influences the pace of the first wave of spermatogenesis, providing new clues to causes of altered pubertal development in boys.

scholarly journals Abnormal Meiosis Initiation in Germ Cell Caused by Aberrant Differentiation of Gonad Somatic Cell

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Min Chen ◽  
Min Chen ◽  
Suren Chen ◽  
Jingjing Zhou ◽  
Fangfang Dong ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Germ Cell ◽  
Somatic Cell ◽  
Germ Cells ◽  
Somatic Cells ◽  
Ectopic Expression ◽  
Genital Ridge ◽  
Male And Female ◽  
Germ Cell Differentiation ◽  
Exact Function

The interaction between germ cell and somatic cell plays important roles in germ cell development. However, the exact function of gonad somatic cell in germ cell differentiation is unclear. In the present study, the function of gonad somatic cell in germ cell meiosis was examined by using mouse models with aberrant somatic cell differentiation. In Wt1R394W/R394W mice, the genital ridge is absent due to the apoptosis of coelomic epithelial cells. Interestingly, in both male and female Wt1R394W/R394W germ cells, STRA8 was detected at E12.5 and the scattered SYCP3 foci were observed at E13.5 which was consistent with control females. In Wt1-/flox; Cre-ERTM mice, Wt1 was inactivated by the injection of tamoxifen at E9.5 and the differentiation of Sertoli and granulosa cells was completely blocked. We found that most germ cells were located outside of genital ridge after Wt1 inactivation. STRA8, SYCP3, and γH2AX proteins were detected in germ cells of both male and female Wt1-/flox; Cre-ERTM gonads, whereas no thread-like SYCP3 signal was observed. Our study demonstrates that aberrant development of gonad somatic cells leads to ectopic expression of meiosis-associated genes in germ cells, but meiosis was arrested before prophase I. These results suggest that the proper differentiation of gonad somatic cells is essential for germ cell meiosis.

scholarly journals Exogenous Gonadotrophin Stimulation Induces Partial Maturation of Human Sertoli Cells in a Testicular Xenotransplantation Model for Fertility Preservation

2020 ◽  
Vol 9 (1) ◽  
pp. 266 ◽  
Author(s):  
Marsida Hutka ◽  
Lee B. Smith ◽  
Ellen Goossens ◽  
W. Hamish B. Wallace ◽  
Jan-Bernd Stukenborg ◽  
...  
Keyword(s):  
Sertoli Cell ◽  
Sertoli Cells ◽  
Connexin 43 ◽  
Xenograft Model ◽  
Cell Maturation ◽  
Human Testis ◽  
Testicular Development ◽  
Future Fertility ◽  
And Function ◽  
Testis Tissue

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.

scholarly journals Sox3 Functions in a Cell-Autonomous Manner to Regulate Spermatogonial Differentiation in Mice

Endocrinology ◽  
2011 ◽  
Vol 152 (4) ◽  
pp. 1606-1615 ◽  
Author(s):  
Monica M. Laronda ◽  
J. Larry Jameson
Keyword(s):  
Tyrosine Kinase ◽  
Germ Cell ◽  
Germ Cells ◽  
High Mobility ◽  
Nuclear Antigen ◽  
Gradual Transition ◽  
Tyrosine Kinase Receptor ◽  
Germ Cell Differentiation ◽  
Expression Of Genes ◽  
Complex Protein

Abstract The X-linked Sox3 gene encodes a member of the Sry high-mobility group box proteins, which play a role in many developmental processes including neurogenesis and testis development. This study further examined the role of Sox3 in spermatogenesis. Males without Sox3 expression exhibited a similar number of germ cell nuclear antigen-positive germ cells at 1, 5, and 10 d postpartum (dpp) compared to their wild-type littermates, but there was significant germ cell depletion by 20 dpp. However, spermatogenesis later resumed and postmeiotic germ cells were observed by 56 dpp. The VasaCre transgene was used to generate a germ cell-specific deletion of Sox3. The phenotype of the germ cell-specific Sox3 knockout was similar to the ubiquitous knockout, indicating an intrinsic role for Sox3 in germ cells. The residual germ cells in 20 dpp Sox3−/Y males were spermatogonia as indicated by their expression of neurogenin3 but not synaptonemal complex protein 3, which is expressed within cells undergoing meiosis. RNA expression analyses corroborated the histological analyses and revealed a gradual transition from relatively increased expression of spermatogonia genes at 20 dpp to near normal expression of genes characteristic of undifferentiated and meiotic germ cells by 84 dpp. Fluorescent-activated cell sorting of undifferentiated (ret tyrosine kinase receptor positive) and differentiated (kit receptor tyrosine kinase-positive) spermatogonia revealed depletion of differentiated spermatogonia in Sox3−/Y tubules. These results indicate that Sox3 functions in an intrinsic manner to promote differentiation of spermatogonia in prepubertal mice but it is not required for ongoing spermatogenesis in adults. The Sox3−/Y males provide a unique model for studying the mechanism of germ cell differentiation in prepubertal testes.

scholarly journals Abnormalities of Germ Cell Maturation and Sertoli Cell Cytoskeleton in Androgen Receptor 113 CAG Knock-In Mice Reveal Toxic Effects of the Mutant Protein

2006 ◽  
Vol 168 (1) ◽  
pp. 195-204 ◽  
Author(s):  
Zhigang Yu ◽  
Nahid Dadgar ◽  
Megan Albertelli ◽  
Arno Scheller ◽  
Roger L. Albin ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Germ Cell ◽  
Sertoli Cell ◽  
Toxic Effects ◽  
Cell Maturation ◽  
Mutant Protein ◽  
Cell Cytoskeleton

scholarly journals Morphological changes of Sertoli cells during the male reproductive cycle of the teleost Piaractus mesopotamicus (Holmberg, 1887)

2005 ◽  
Vol 65 (2) ◽  
pp. 241-249 ◽  
Author(s):  
C. Cruz-Landim ◽  
F. C. Abdalla ◽  
M. A. Cruz-Höfling
Keyword(s):  
Germ Cell ◽  
Sertoli Cell ◽  
Reproductive Cycle ◽  
Sertoli Cells ◽  
Morphological Changes ◽  
Cell Development ◽  
Cell Maturation ◽  
Ultrastructural Changes ◽  
Piaractus Mesopotamicus

An investigation of the histological and ultrastructural changes of Sertoli cells during the male reproductive cycle in Piaractus mesopotamicus was made. The results showed that the Sertoli cell development is closely related with germ cell maturation. Therefore, these cells may have some role in germ cell maturation during the reproductive cycle of this species, whether in forming a tissue framework for the developing spermatogenic cysts, aiding in testes reorganization for a new reproductive cycle, in addition to other possible functions discussed in the text.

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