CX43 expression, phosphorylation, and distribution in the normal and autoimmune orchitic testis with a look at gap junctions joining germ cell to germ cell

2011 ◽  
Vol 300 (1) ◽  
pp. R121-R139 ◽  
Author(s):  
R.-Marc Pelletier ◽  
Casimir D. Akpovi ◽  
Li Chen ◽  
Robert Day ◽  
María L. Vitale
Keyword(s):  
Cell Differentiation ◽  
Gap Junctions ◽  
Germ Cell ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Seminiferous Tubule ◽  
Connexin 43 ◽  
Cx43 Expression ◽  
Cx43 Protein ◽  
Cx43 Mrna

Spermatogenesis requires connexin 43 (Cx43).This study examines normal gene transcription, translation, and phosphorylation of Cx43 to define its role on germ cell growth and Sertoli cell's differentiation, and identifies abnormalities arising from spontaneous autoimmune orchitis (AIO) in mink, a seasonal breeder and a natural model for autoimmunity. Northern blot analysis detected 2.8- and a 3.7-kb Cx43 mRNA bands in seminiferous tubule-enriched fractions. Cx43 mRNA increased in seminiferous tubule-enriched fractions throughout development and then seasonally with the completion of spermatogenesis. Cx43 protein levels increased transiently during the colonization of the tubules by the early-stage spermatocytes. Cx43 phosphorylated (PCx43) and nonphosphorylated (NPCx43) in Ser368 decreased during the periods of completion of meiosis and Sertoli cell differentiation, while Cx43 mRNA remained elevated throughout. PCx43 labeled chiefly the plasma membrane except by stage VII when vesicles were also labeled in Sertoli cells. Vesicles and lysosomes in Sertoli cells and the Golgi apparatus in the round spermatids were NPCx43 positive. A decrease in Cx43 gene expression was matched by a Cx43 protein increase in the early, not the late, phase of AIO. Total Cx43 and PCx43 decreased with the advance of orchitis. The study makes a novel finding of gap junctions connecting germ cells. The data indicate that Cx43 protein expression and phosphorylation in Ser368 are stage-specific events that may locally influence the acquisition of meiotic competence and the Sertoli cell differentiation in normal testis. AIO modifies Cx43 levels, suggesting changes in Cx43-mediated intercommunication and spermatogenic activity in response to cytokines imbalances in Sertoli cells.

Focal Orchitis in Undescended Testes

2002 ◽  
Vol 126 (1) ◽  
pp. 64-69
Author(s):  
Manuel Nistal ◽  
María Luisa Riestra ◽  
Ricardo Paniagua
Keyword(s):  
Germ Cell ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Seminiferous Tubule ◽  
Immune Cell ◽  
Laboratory Data ◽  
Rete Testis ◽  
Seminiferous Tubules ◽  
Inflammatory Infiltrates ◽  
Lymphoid Infiltrates

Abstract Objective.—To evaluate seminiferous epithelium lesions in adult cryptorchid testes showing lymphoid infiltrates in seminiferous tubules and interstitium (ie, focal orchitis). Also, to consider the possible role of this lesion in the etiology of tubular atrophy. Methods.—We performed a histopathologic study of the cryptorchid testes and adjacent epididymides removed from 50 adult men who had not been previously treated for cryptorchidism. The study included morphologic and semiquantitative evaluation of seminiferous tubule pathology (according to germ cell numbers), Sertoli cell morphology, tubular lumen dilation, rete testis pattern (normal, hypoplastic, or cystic), and epididymal pattern (normal or epididymal duct hypoplasia). The study also included immunohistochemical evaluation of immune cell markers. The results were compared with clinical and laboratory findings. Results.—Focal lymphoid infiltrates (mainly lymphocytes) in seminiferous tubules and interstitium were found in 22 patients (44%), all of whom had unilateral cryptorchidism. The course of orchitis was asymptomatic, and laboratory data were normal. According to the seminiferous tubule pathology, a variety of histopathologic diagnoses, were made: (1) mixed atrophy consisting of Sertoli cell–only tubules intermingled with tubules showing maturation arrest of spermatogonia (11 testes, 4 of which also showed hyalinized tubules); (2) Sertoli cell–only tubules plus hyalinized tubules (4 testes); (3) Sertoli cell–only tubules (3 testes); (4) intratubular germ cell neoplasia (2 testes, 1 of which also showed hyalinized tubules); (5) complete tubular hyalinization (1 testis); and (6) tubular hyalinization plus some groups of tubules with hypospermatogenesis (all germ cell types were present although in lower numbers, 1 testis). Dysgenetic Sertoli cells, that is, Sertoli cells that had undergone anomalous, incomplete maturation, were observed in all nonhyalinized seminiferous tubules with inflammatory infiltrates. Tubular ectasia was observed in 13 cases. The rete testis was hypoplastic and showed cystic transformation in 18 testes, and the epididymis was hypoplastic in 15 testes. Conclusions.—The causes of these focal inflammatory infiltrates are unknown. It is possible that tubular ectasia and Sertoli cell dysgenesis are involved and that these alterations cause a disruption of the blood-testis barrier and allow antigens to enter the testicular interstitium, giving rise to an autoimmune process.

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.

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 Extracellular matrix regulates Sertoli cell differentiation, testicular cord formation, and germ cell development in vitro.

1985 ◽  
Vol 101 (4) ◽  
pp. 1511-1522 ◽  
Author(s):  
M A Hadley ◽  
S W Byers ◽  
C A Suárez-Quian ◽  
H K Kleinman ◽  
M Dym
Keyword(s):  
Extracellular Matrix ◽  
Cell Differentiation ◽  
Basement Membrane ◽  
Germ Cell ◽  
Sertoli Cell ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Type I ◽  
Extracellular Matrix Components

Sertoli cell preparations isolated from 10-day-old rats were cultured on three different substrates: plastic, a matrix deposited by co-culture of Sertoli and peritubular myoid cells, and a reconstituted basement membrane gel from the EHS tumor. When grown on plastic, Sertoli cells formed a squamous monolayer that did not retain contaminating germ cells. Grown on the matrix deposited by Sertoli-myoid cell co-cultures, Sertoli cells were more cuboidal and supported some germ cells but did not allow them to differentiate. After 3 wk however, the Sertoli cells flattened to resemble those grown on plastic. In contrast, the Sertoli cells grown on top of the reconstituted basement membrane formed polarized monolayers virtually identical to Sertoli cells in vivo. They were columnar with an elaborate cytoskeleton. In addition, they had characteristic basally located tight junctions and maintained germ cells for at least 5 wk in the basal aspect of the monolayer. However, germ cells did not differentiate. Total protein, androgen binding protein, transferrin, and type I collagen secretion were markedly greater when Sertoli cells were grown on the extracellular matrices than when they were grown on plastic. When Sertoli cells were cultured within rather than on top of reconstituted basement membrane gels they reorganized into cords. After one week, tight junctional complexes formed between adjacent Sertoli cells, functionally compartmentalizing the cords into central (adluminal) and peripheral (basal) compartments. Germ cells within the cords continued to differentiate. Thus, Sertoli cells cultured on top of extracellular matrix components assume a phenotype and morphology more characteristic of the in vivo, differentiated cells. Growing Sertoli cells within reconstituted basement membrane gels induces a morphogenesis of the cells into cords, which closely resemble the organ from which the cells were dissociated and which provide an environment permissive for germ cell differentiation.

Germ Cell-Sertoli Cell Interactions Studies of Cyclic Protein-2 in the Seminiferous Tubule

1989 ◽  
Vol 564 (1 Regulation of) ◽  
pp. 173-185 ◽  
Author(s):  
WILLIAM W. WRIGHT ◽  
SONYA D. ZABLUDOFF ◽  
MOIRA ERICKSON-LAWRENCE ◽  
ABDUL W. KARZAI
Keyword(s):  
Germ Cell ◽  
Sertoli Cell ◽  
Seminiferous Tubule ◽  
Cell Interactions

Role of FSH and triiodothyronine in Sertoli cell development expressed by formation of connexin 43-based gap junctions

2011 ◽  
Vol 315A (6) ◽  
pp. 329-336 ◽  
Author(s):  
Katarzyna Marchlewska ◽  
Krzysztof Kula ◽  
Renata Walczak-Jedrzejowska ◽  
Elzbieta Oszukowska ◽  
Eliza Filipiak ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Sertoli Cell ◽  
Connexin 43 ◽  
Cell Development

scholarly journals Cell-type-specific regulation of genes involved in testicular lipid metabolism: fatty acid-binding proteins, diacylglycerol acyltransferases, and perilipin 2

Reproduction ◽  
2013 ◽  
Vol 146 (5) ◽  
pp. 471-480 ◽  
Author(s):  
Gerardo M Oresti ◽  
Jesús García-López ◽  
Marta I Aveldaño ◽  
Jesús del Mazo
Keyword(s):  
Fatty Acid ◽  
Cell Differentiation ◽  
Germ Cell ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Fatty Acid Binding Proteins ◽  
Cell Type ◽  
Fatty Acid Binding ◽  
Germ Cell Differentiation ◽  
Perilipin 2

Male germ cell differentiation entails the synthesis and remodeling of membrane polar lipids and the formation of triacylglycerols (TAGs). This requires fatty acid-binding proteins (FABPs) for intracellular fatty acid traffic, a diacylglycerol acyltransferase (DGAT) to catalyze the final step of TAG biosynthesis, and a TAG storage mode. We examined the expression of genes encoding five members of the FABP family and two DGAT proteins, as well as the lipid droplet protein perilipin 2 (PLIN2), during mouse testis development and in specific cells from seminiferous epithelium.Fabp5expression was distinctive of Sertoli cells and consequently was higher in prepubertal than in adult testis. The expression ofFabp3increased in testis during postnatal development, associated with the functional differentiation of interstitial cells, but was low in germ cells.Fabp9, together withFabp12, was prominently expressed in the latter. Their transcripts increased from spermatocytes to spermatids and, interestingly, were highest in spermatid-derived residual bodies (RB). Both Sertoli and germ cells, which produce neutral lipids and store them in lipid droplets, expressedPlin2. Yet, whileDgat1was detected in Sertoli cells,Dgat2accumulated in germ cells with a similar pattern of expression asFabp9. These results correlated with polyunsaturated fatty acid-rich TAG levels also increasing with mouse germ cell differentiation highest in RB, connecting DGAT2 with the biosynthesis of such TAGs. The age- and germ cell type-associated increases inFabp9,Dgat2, andPlin2levels are thus functionally related in the last stages of germ cell differentiation.

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.

Role of mammalian Y chromosome in sex determination

1988 ◽  
Vol 322 (1208) ◽  
pp. 63-72 ◽  
Keyword(s):  
Cell Differentiation ◽  
Sex Determination ◽  
Y Chromosome ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Sex Reversal ◽  
Testicular Development ◽  
Chimeric Mouse ◽  
Embryonic Gonad

It has long been assumed that the mammalian Y chromosome either encodes, or controls the production of, a diffusible testis-determining molecule, exposure of the embryonic gonad to this molecule being all that is required to divert it along the testicular pathway. My recent finding that Sertoli cells in XX ↔ XY chimeric mouse testes are exclusively XY has led me to propose a new model in which the Y acts cell-autonomously to bring about Sertoli-cell differentiation. I have suggested that all other aspects of foetal testicular development are triggered by the Sertoli cells without further Y-chromosome involvement. This model thus equates mammalian sex determination with Sertoli-cell determination. Examples of natural and experimentally induced sex reversal are discussed in the context of this model.

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