Sertoli Cell-Germ Cell Communication

1989 ◽  
Vol 564 (1 Regulation of) ◽  
pp. 232-242 ◽  
Author(s):  
J. ANTON GROOTEGOED ◽  
PIET J. DEN BOER ◽  
PETRA MACKENBACH
2015 ◽  
Vol 309 (3) ◽  
pp. R255-R276 ◽  
Author(s):  
R.-Marc Pelletier ◽  
Casimir D. Akpovi ◽  
Li Chen ◽  
Nalin M. Kumar ◽  
María L. Vitale

Gap junction-mediated communication helps synchronize interconnected Sertoli cell activities. Besides, coordination of germ cell and Sertoli cell activities depends on gap junction-mediated Sertoli cell–germ cell communication. This report assesses mechanisms underlying the regulation of connexin 46 (Cx46) and Cx50 in mouse testis and those accompanying a “natural” seasonal and a pathological arrest of spermatogenesis, resulting from autoimmune orchitis (AIO) in mink. Furthermore, the impact of deleting Cx46 or Cx50 on the expression, phosphorylation of junction proteins, and spermatogenesis is evaluated. Cx46 mRNA and protein expression increased, whereas Cx50 decreased with adulthood in normal mice and mink. Cx46 mRNA and protein expression increased, whereas Cx50 decreased with adulthood in normal mice and mink. During the mink active spermatogenic phase, Cx50 became phosphorylated and localized to the site of the blood-testis barrier. By contrast, Cx46 was dephosphorylated and associated with annular junctions, suggesting phosphorylation/dephosphorylation of Cx46 and Cx50 involvement in the barrier dynamics. Cx46-positive annular junctions in contact with lipid droplets were found. Cx46 and Cx50 expression and localization were altered in mink with AIO. The deletion of Cx46 or Cx50 impacted on other connexin expression and phosphorylation and differently affected tight and adhering junction protein expression. The level of apoptosis, determined by ELISA, and a number of Apostain-labeled spermatocytes and spermatids/tubules were higher in mice lacking Cx46 ( Cx46−/−) than wild-type and Cx50−/− mice, arguing for life-sustaining Cx46 gap junction-mediated exchanges in late-stage germ cells secluded from the blood by the barrier. The data show that expression and phosphorylation of Cx46 and Cx50 are complementary in seminiferous tubules.


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

Genes ◽  
2022 ◽  
Vol 13 (1) ◽  
pp. 151
Author(s):  
Kenta Nagahori ◽  
Ning Qu ◽  
Miyuki Kuramasu ◽  
Yuki Ogawa ◽  
Daisuke Kiyoshima ◽  
...  

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.


2011 ◽  
Vol 300 (1) ◽  
pp. R121-R139 ◽  
Author(s):  
R.-Marc Pelletier ◽  
Casimir D. Akpovi ◽  
Li Chen ◽  
Robert Day ◽  
María L. Vitale

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.


Endocrinology ◽  
2011 ◽  
Vol 152 (5) ◽  
pp. 2076-2089 ◽  
Author(s):  
Catherine Itman ◽  
Chin Wong ◽  
Briony Hunyadi ◽  
Matthias Ernst ◽  
David A. Jans ◽  
...  

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.


2008 ◽  
Vol 132 (4) ◽  
pp. 548-564 ◽  
Author(s):  
Robert H. Young

Abstract The histopathology of testicular tumors is presented, emphasizing new, unusual, or underemphasized aspects. Within the category of seminoma of the usual type, the recent literature has drawn attention to the presence in occasional tumors of solid or hollow tubules or spaces of varying sizes and shape that may result in cribriform or microcystic patterns, causing potential confusion with other neoplasms, most notably Sertoli cell tumor or yolk sac tumor. Although regions of typical neoplasia and awareness of this phenomenon usually will be diagnostic, immunohistochemistry may play a role in excluding Sertoli cell tumor or yolk sac tumor. Although immunohistochemistry can play an undoubted helpful role in this and selected other areas of testicular tumor evaluation, careful evaluation of the gross and routine microscopic features will solve the vast majority of diagnostic problems. An excellent review of immunohistochemistry in this area by R. E. Emerson, MD, and T. M. Ulbright, MD, is cited herein. Spermatocytic seminoma remains a crucial pitfall in diagnosis, and the pathologist must always be alert to the possible diagnosis when looking at a seminomatous neoplasm, particularly in an older patient, although about one third of these tumors occur in the usual seminoma age range. The embryonal carcinoma has a great diversity of patterns, which are briefly noted. The enigmatic and picturesque tumor, polyembryoma, which virtually never occurs in pure form but may be a confusing component of a variety of mixed germ cell tumors, is discussed and illustrated. The phenomenon of burnt-out germ cell neoplasia is also briefly noted and an excellent recent contribution is referred to. Within the sex cord–stromal family of neoplasms, recent contributions and elaborations of unusual morphologic features of Leydig cell tumors and Sertoli cell tumors are presented. Within the Leydig cell family, cyst formation, adipose metaplasia, calcification or ossification, and spindle cell patterns may be particularly confusing, and in the Sertoli cell family, a great array of patterns caused by differing admixtures of tubular, solid, and stromal components occur. The peculiar lesion, intratubular large cell hyalinizing Sertoli cell tumor, of young boys with Peutz-Jeghers syndrome, is briefly discussed. Some of the problems in the family of hematopoietic neoplasms are reviewed, these processes posing diverse problems in differential diagnosis and their correct recognition having crucial therapeutic implications. Although secondary tumors to the testis have not received the same attention in the literature as the similar phenomenon in the female gonad, remarkable examples of testicular spread of diverse neoplasms, usually carcinoma but rarely melanoma, are seen, and the pathologist should be alert to this possibility, particularly when examining an unusual morphology in an older patient. Finally, a few comments are made on the common paratesticular neoplasm, the adenomatoid tumor, highlighting its varied patterns and recent description of some of the issues that may arise when they undergo total or subtotal infarction.


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