Effects of a murine germ cell-specific knockout of Connexin 43 on Connexin expression in testis and fertility

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.

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Blood Testis Barrier and Somatic Cells Impairment in a Series of 35 Adult Klinefelter Syndrome Patients

International Journal of Molecular Sciences ◽

10.3390/ijms20225717 ◽

2019 ◽

Vol 20 (22) ◽

pp. 5717 ◽

Cited By ~ 7

Author(s):

Giudice ◽

Vermeulen ◽

Wyns

Keyword(s):

Germ Cell ◽

Connexin 43 ◽

Klinefelter Syndrome ◽

Cell Loss ◽

Testicular Tissue ◽

Seminiferous Tubules ◽

Morphological Alterations ◽

Normal Spermatogenesis ◽

Underlying Mechanisms ◽

Blood Testis Barrier

Klinefelter Syndrome (KS) is the most common genetic cause of infertility in men. Degeneration of the testicular tissue starts in utero and accelerates at puberty with hyalinisation of seminiferous tubules, spermatogonia apoptosis and germ cell maturation arrest. Therefore, fertility preservation in young KS boys has been proposed, although this measure is still debated due to insufficient knowledge of the pathophysiology of the disease. To better understand the underlying mechanisms of testicular failure and germ cell loss, we analysed functional and morphological alterations in the somatic compartment of KS testis, i.e., Sertoli cells, including the blood–testis barrier (BTB) and Leydig cells (LC). We compared three populations: 35 KS 47,XXY non-mosaic patients, 28 Sertoli-cell-only (SCO) syndrome patients and 9 patients with normal spermatogenesis. In KS patients the expression of BTB proteins connexin-43 and claudin-11 assessed with a semi-quantitative scoring system appeared significantly reduced with a disorganised pattern. A significant reduction in seminiferous tubules expressing androgen receptors (AR) was observed in KS compared to normal spermatogenesis controls. INSL3 expression, a marker of LC maturation, was also significantly reduced in KS compared to patients with normal spermatogenesis or SCO. Hence, the somatic compartment impairment in KS could be involved in degeneration of seminiferous tubules.

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

Reproductive Biology ◽

10.1016/j.repbio.2018.08.001 ◽

2018 ◽

Vol 18 (4) ◽

pp. 456-466 ◽

Cited By ~ 7

Author(s):

Kristina Rode ◽

Karola Weider ◽

Oliver Siegfried Damm ◽

Joachim Wistuba ◽

Marion Langeheine ◽

...

Keyword(s):

Germ Cell ◽

Sertoli Cells ◽

Connexin 43 ◽

Cell Numbers

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The anti-mitotic drug griseofulvin induces apoptosis of human germ cell tumor cells through a connexin 43-dependent molecular mechanism

APOPTOSIS ◽

10.1007/s10495-012-0800-8 ◽

2013 ◽

Vol 18 (4) ◽

pp. 480-491 ◽

Cited By ~ 13

Author(s):

V. Mauro ◽

D. Carette ◽

R. Pontier-Bres ◽

J. Dompierre ◽

D. Czerucka ◽

...

Keyword(s):

Germ Cell ◽

Tumor Cells ◽

Molecular Mechanism ◽

Germ Cell Tumor ◽

Connexin 43 ◽

Cell Tumor ◽

Human Germ Cell Tumor

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Antagonistic Functions of Connexin 43 during the Development of Primary or Secondary Bone Tumors

Biomolecules ◽

10.3390/biom10091240 ◽

2020 ◽

Vol 10 (9) ◽

pp. 1240

Author(s):

Julie Talbot ◽

Maryne Dupuy ◽

Sarah Morice ◽

Françoise Rédini ◽

Franck Verrecchia

Keyword(s):

Tumor Cells ◽

Connexin 43 ◽

Bone Tumors ◽

Tumor Promoter ◽

Gap Junctional Intercellular Communication ◽

Membrane Structures ◽

Connexin Expression ◽

Primary Bone Tumors ◽

Tumor Dissemination ◽

Primary Bone

Despite research and clinical advances during recent decades, bone cancers remain a leading cause of death worldwide. There is a low survival rate for patients with primary bone tumors such as osteosarcoma and Ewing’s sarcoma or secondary bone tumors such as bone metastases from prostate carcinoma. Gap junctions are specialized plasma membrane structures consisting of transmembrane channels that directly link the cytoplasm of adjacent cells, thereby enabling the direct exchange of small signaling molecules between cells. Discoveries of human genetic disorders due to genetic mutations in gap junction proteins (connexins) and experimental data using connexin knockout mice have provided significant evidence that gap-junctional intercellular communication (Gj) is crucial for tissue function. Thus, the dysfunction of Gj may be responsible for the development of some diseases. Gj is thus a main mechanism for tumor cells to communicate with other tumor cells and their surrounding microenvironment to survive and proliferate. If it is well accepted that a low level of connexin expression favors cancer cell proliferation and therefore primary tumor development, more evidence is suggesting that a high level of connexin expression stimulates various cellular process such as intravasation, extravasation, or migration of metastatic cells. If so, connexin expression would facilitate secondary tumor dissemination. This paper discusses evidence that suggests that connexin 43 plays an antagonistic role in the development of primary bone tumors as a tumor suppressor and secondary bone tumors as a tumor promoter.

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Primordial germ cell deficiency in the connexin 43 knockout mouse arises from apoptosis associated with abnormal p53 activation

Development ◽

10.1242/dev.02506 ◽

2006 ◽

Vol 133 (17) ◽

pp. 3451-3460 ◽

Cited By ~ 37

Author(s):

R. J. B. Francis

Keyword(s):

Germ Cell ◽

Knockout Mouse ◽

Connexin 43 ◽

Primordial Germ Cell ◽

P53 Activation

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Connexin 43 Antisense Therapy Modulates Connexin Expression and Wound Repair in Nitrogen Mustard Injured Mouse Skin

The FASEB Journal ◽

10.1096/fasebj.29.1_supplement.876.3 ◽

2015 ◽

Vol 29 (S1) ◽

Author(s):

Yoke‐chen Chang ◽

Hui‐Ying Chang ◽

Rita Hahn ◽

Esther Lee ◽

Kathy Svoboda ◽

...

Keyword(s):

Connexin 43 ◽

Wound Repair ◽

Nitrogen Mustard ◽

Mouse Skin ◽

Connexin Expression ◽

Antisense Therapy

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Electron microscope study of the effects of radiation on insect fertility

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100157905 ◽

1990 ◽

Vol 48 (3) ◽

pp. 72-73

Author(s):

Judy Ju-Hu Chiang ◽

Robert Kuo-Cheng Chen

Keyword(s):

Electron Microscopy ◽

Germ Cell ◽

Germ Cells ◽

Electron Microscope Study ◽

Radiation Treatment ◽

Light And Electron Microscopy ◽

Stem Borer ◽

Metabolic Energy ◽

Rice Stem Borer ◽

Effects Of Radiation

Germ cells from the rice stem borer Chilo suppresalis, were examined by light and electron microscopy. Damages to organelles within the germ cells were observed. The mitochondria, which provide the cell with metabolic energy, were seen to disintegrate within the germ cell. Lysosomes within the germ cell were also seen to disintegrate. The subsequent release of hydrolytic enzymesmay be responsible for the destruction of organelles within the germ cell. Insect spermatozoa were seen to lose the ability to move because of radiation treatment. Damage to the centrioles, one of which is in contact with the tail, may be involved in causing sperm immobility.

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