Testicular connexin 43, a precocious molecular target for the effect of environmental toxicants on male fertility

Pointis, Georges; Gilleron, Jérôme; Carette, Diane; Segretain, Dominique

doi:10.4161/spmg.1.4.18392

Cited by 63 publications

(39 citation statements)

References 164 publications

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“…Indeed, gonocytes were found to be associated to Sertoli cells via gap and desmosomelike junctions, believed to regulate communication between these cells [9]. A variety of cell adhesion molecules were found in gonocytes and Sertoli cells, including NCAM [10], PB-cadherin [11], and connexin 43 [12,13]. Thus, in order to migrate to the basement membrane, neonatal gonocytes need to free themselves from junctions with Sertoli cells and migrate between the lateral surfaces of adjacent Sertoli cells.…”

Section: Gonocyte Characteristicsmentioning

confidence: 99%

Gonocytes, from the Fifties to the Present: Is There a Reason to Change the Name?1

Culty

2013

Biology of Reproduction

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Historically, the precursor cells to spermatogonia have been identified as "gonocytes," a term created in the fifties to encompass fetal and neonatal germ cells from the time they become resident in testis primordia to the time they relocate at the basement membrane of the seminiferous cords and differentiate. During this period, spreading over several days in rodents and months in humans, germ cell morphology and central location within the cords remain relatively unchanged. Another common trait is the intensive DNA methylation taking place in fetal to neonatal gonocytes. It is only when they reach the periphery of the cords after birth that germ cells acquire the characteristic appearance of spermatogonia. Studies showed that fetal and neonatal germ cells undergo progressive developmental changes comprising three major phases, a fetal mitotic phase followed by a quiescent period during which most of DNA methylation occurs and a neonatal mitotic phase associated with migration to the basement membrane, morphological changes, and differentiation to spermatogonia. Efforts to associate a distinctive gene expression profile to each of these phases have failed, revealing instead gradual changes in gene and protein expression and the coexistence within each period of unsynchronized cells at different phases of development. In the seventies, the terms pre- or prospermatogonia appeared as alternatives for the term gonocytes, but the definition of these terminologies varied between studies. Thus far, the term gonocyte remains the most commonly used, corresponding to a specific location of the cells, morphological appearance, and functional traits, which are distinct from the prior and subsequent developmental phases. In view of the present knowledge, one could further distinguish gonocyte subsets by the prefixes M, Q, and T, describing, respectively, fetal mitotic, quiescent, and transitional neonatal mitotic/migratory gonocytes, in conjunction with emerging methods allowing better discrimination of these subsets.

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Section: Gonocyte Characteristicsmentioning

confidence: 99%

Gonocytes, from the Fifties to the Present: Is There a Reason to Change the Name?1

Culty

2013

Biology of Reproduction

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“…Additionally, Sertoli cells serve as the scavenger to remove apoptotic germ cells and other cellular debris as they arise during spermatogenesis through phagocytosis. Similar to the Leydig cell, EDCs also target the Sertoli cell, disturbing hormone or protein secretions, inducing oxidative stress, blocking GJ communications and damaging the BTB integrity, contributing to infertility [5,42-45]. …”

Section: Impact Of Edcs On Sperm Production In the Testis Through mentioning

confidence: 99%

Targeting testis-specific proteins to inhibit spermatogenesis: lesson from endocrine disrupting chemicals

Wan

Mruk

Wong

et al. 2013

Expert Opinion on Therapeutic Targets

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Introduction Exposure to endocrine disrupting chemicals (EDCs) has recently been linked to declining fertility in men in both developed and developing countries. Since many EDCs possess intrinsic estrogenic or androgenic activities, thus, the gonad is one of the major targets of EDCs. Areas covered For the past 2 decades, studies found in the literature regarding the disruptive effects of these EDCs on reproductive function in human males and also rodents were mostly focused on oxidative stress-induced germ cell apoptosis, disruption of steroidogenesis, abnormal sperm production and disruption of spermatogenesis in particular cell adhesion function and the blood–testis-barrier (BTB) function. Herein, we highlight recent findings in the field illustrating testis-specific proteins are also targets of EDCs. Expert opinion This information should be helpful in developing better therapeutic approach to manage ECD-induced reproductive toxicity. This information is also helpful to identify potential targets for male contraceptive development.

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“…It may also be mentionable in this context that it was reported in different studies that BTB components may act as early targets of environmental and reproductive toxicants mostly leading to testicular disorders (Defamie et al 2001, Sobarzo et al 2006, 2009, Li et al 2009a, Salian et al 2009, Pointis et al 2011.…”

Section: Sc Btb and Junctional Proteinsmentioning

confidence: 99%

Blood–testis barrier and Sertoli cell function: lessons from SCCx43KO mice

Gerber¹,

Heinrich²,

Brehm³

2016

Reproduction

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The gap junction protein connexin43 (CX43) plays a vital role in mammalian spermatogenesis by allowing for direct cytoplasmic communication between neighbouring testicular cells. In addition, different publications suggest that CX43 in Sertoli cells (SC) might be important for blood-testis barrier (BTB) formation and BTB homeostasis. Thus, through the use of the Cre-LoxP recombination system, a transgenic mouse line was developed in which only SC are deficient of the gap junction protein, alpha 1 (Gja1) gene. Gja1 codes for the protein CX43. This transgenic mouse line has been commonly defined as the SC specific CX43 knockout (SCCx43KO) mouse line. Within the seminiferous tubule, SC aid in spermatogenesis by nurturing germ cells and help them to proliferate and mature. Owing to the absence of CX43 within the SC, homozygous KO mice are infertile, have reduced testis size, and mainly exhibit spermatogenesis arrest at the level of spermatogonia, seminiferous tubules containing only SC (SC-only syndrome) and intratubular SC-clusters. Although the SC specific KO of CX43 does not seem to have an adverse effect on BTB integrity, CX43 influences BTB composition as the expression pattern of different BTB proteins (like OCCLUDIN, b-CATENIN, N-CADHERIN, and CLAUDIN11) is altered in mutant males. The supposed roles of CX43 in dynamic BTB regulation, BTB assembly and/or disassembly and its possible interaction with other junctional proteins composing this unique barrier are discussed. Data collectively indicate that CX43 might represent an important regulator of dynamic BTB formation, composition and function.Reproduction (2016) 151 R15-R27

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Testicular connexin 43, a precocious molecular target for the effect of environmental toxicants on male fertility

Cited by 63 publications

References 164 publications

Gonocytes, from the Fifties to the Present: Is There a Reason to Change the Name?1

Gonocytes, from the Fifties to the Present: Is There a Reason to Change the Name?1

Targeting testis-specific proteins to inhibit spermatogenesis: lesson from endocrine disrupting chemicals

Blood–testis barrier and Sertoli cell function: lessons from SCCx43KO mice

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