Neonatal exposure of male rats to Bisphenol A impairs fertility and expression of sertoli cell junctional proteins in the testis

Salian, Smita; Doshi, Tanvi; Vanage, Geeta

doi:10.1016/j.tox.2009.09.012

Cited by 221 publications

(168 citation statements)

References 41 publications

Supporting

Mentioning

160

Contrasting

Order By: Relevance

“…The loss of Cx43 could lead to the failure of spermatogenesis [Bozec et al 2004;Cyr 2011;Lampe and Lau 2004;Salian et al 2009]. In this current study, a significant decrease in the level of Cx43 protein expression was observed in the testes of Flu-exposed rats compared with controls on PD20 (p50.01; Figure 1A-C, Table 1).…”

Section: Pd20 Are Shown Insupporting

confidence: 50%

Connexin 43 expression in Sprague-Dawley rat seminiferous epithelium afterin uteroexposure to flutamide

Cai

Zhao

et al. 2014

Systems Biology in Reproductive Medicine

View full text Add to dashboard Cite

This study explored the expression of connexin 43 (Cx43) in the testes of prepubertal SpragueDawley (SD) rats following in utero flutamide (Flu) exposure. Connexins constitute the major protein type in gap junctions. Connexin 43, the most prominent connexin family member expressed by testes, is localized at the base of seminiferous tubules in humans and rodents, and may be involved in fertility. Flutamide was injected subcutaneously into pregnant SD rats on gestational days 12-21 (25 mg/kg/day). Immunohistochemistry, Western blotting, and real-time PCR was used to investigate the distribution and the expression of Cx43 protein and mRNA in the testis on postnatal day 20 (PD20). Following Flu-exposure, Cx43 was observed between Sertoli cells in the seminiferous tubules. On PD20, no Cx43 protein was expressed by the spermatogonial cell layer of the seminiferous tubules in the controls, but was observed in the Flu-exposed group. Western blotting showed that Cx43 was expressed at significantly lower levels in Flu-exposed testes than controls on PD20 (p50.001). On PD20, levels of Cx43 mRNA in undescended Flu-exposed testes were significantly lower than in controls (p50.05) and descended Flu-exposed testes (p50.01). After Flu-exposure in the rat embryonic period, Cx43 mRNA and protein expression were downregulated, and its distribution in the seminiferous tubules was abnormal.

show abstract

Section: Pd20 Are Shown Insupporting

confidence: 50%

Connexin 43 expression in Sprague-Dawley rat seminiferous epithelium afterin uteroexposure to flutamide

Cai

Zhao

et al. 2014

Systems Biology in Reproductive Medicine

View full text Add to dashboard Cite

show abstract

“…Because maturation of spermatogenesis requires the establishment of BTB along with differentiation of Sertoli cells, normal spermatogenesis cannot take place in the absence of a functional BTB. A malfunctioning BTB thus leads to infertility or reduced fertility in rodents and humans (18,(20)(21)(22). This postulate is further supported by the findings in claudin-11 −/− mice (claudin-11 is an integral membrane protein at the BTB) wherein Sertoli cells in claudin-11 −/− mice are similarly found to be proliferating and sloughed off into the lumen (23).…”

Section: Discussionmentioning

confidence: 65%

“…In humans, testes with Sertoli cell only syndrome or spermatogenic arrest at the spermatogonial level in infertile men were also correlated with lower levels of Cx43 in seminiferous tubules (20,21). Adult male rats with neonatal exposure to BPA had a lowered level of Cx43 and a smaller litter size, reduced sperm count, and poor sperm motility despite an increase in localization of immunoreactive N-cadherin and ZO-1 near the BTB region (22). Because maturation of spermatogenesis requires the establishment of BTB along with differentiation of Sertoli cells, normal spermatogenesis cannot take place in the absence of a functional BTB.…”

Section: Discussionmentioning

confidence: 97%

Connexin 43 is critical to maintain the homeostasis of the blood–testis barrier via its effects on tight junction reassembly

Mruk²,

Lee³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

146

122

View full text Add to dashboard Cite

In mammalian testes, the blood-testis barrier (BTB) or Sertoli cell barrier created by specialized junctions between Sertoli cells near the basement membrane confers an immunological barrier by sequestering the events of meiotic division and postmeiotic germ cell development from the systemic circulation. The BTB is constituted by coexisting tight junctions (TJs), basal ectoplasmic specializations, desmosomes, and gap junctions. Despite being one of the tightest blood-tissue barriers, the BTB has to restructure cyclically during spermatogenesis. A recent study showed that gap junction protein connexin 43 (Cx43) and desmosome protein plakophilin-2 are working synergistically to modulate the BTB integrity by regulating the distribution of TJ-associated proteins at the Sertoli-Sertoli cell interface. However, the precise role of Cx43 in regulating the cyclical restructuring of junctions remains obscure. In this report, the calcium switch and the bisphenol A (BPA) models were used to induce junction restructuring in primary cultures of Sertoli cells isolated from rat testes that formed a TJ-permeability barrier that mimicked the BTB in vivo. The removal of calcium by EGTA perturbed the Sertoli cell tight junction barrier, but calcium repletion allowed the "resealing" of the disrupted barrier. However, a knockdown of Cx43 in Sertoli cells by RNAi significantly reduced the kinetics of TJ-barrier resealing. These observations were confirmed using the bisphenol A model in which the knockdown of Cx43 by RNAi also perturbed the TJ-barrier reassembly following BPA removal. In summary, Cx43 is crucial for TJ reassembly at the BTB during its cyclic restructuring throughout the seminiferous epithelial cycle of spermatogenesis.bisphenol A | calcium switch | gap junction | seminiferous epithelial cycle | spermatogenesis I n mammalian testes, the blood-testis barrier (BTB) segregates the epithelium of seminiferous tubules into apical and basal compartments (1, 2). Unlike other blood-tissue barriers (e.g., blood-brain barrier, blood-retina barrier) that are constituted by tight junctions (TJs) between endothelial cells of the microvessels at the apical region, the BTB is created by adjacent Sertoli cells in the seminiferous epithelium near the basement membrane. The BTB is constituted by coexisting TJs, basal ectoplasmic specialization (basal ES, a testis-specific adherens junction type), desmosome-like junction (or desmosome-gap junction), and gap junction (GJ) (1-3). Whereas the BTB is one of the tightest blood-tissue barriers, it undergoes cyclical restructuring to accommodate the transit of preleptotene spermatocytes from the basal to the apical compartment during spermatogenesis, so that meiotic divisions and postmeiotic germ cell development (i.e., spermiogenesis) can take place in the apical compartment of the seminiferous epithelium behind this immunological barrier. The immunological barrier conferred by the BTB cannot be compromised, even transiently, during the transit of preleptotene spermatocytes to avoid the product...

show abstract

“…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: 92%

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

Gerber¹,

Heinrich²,

Brehm³

2016

Reproduction

View full text Add to dashboard Cite

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

show abstract

Neonatal exposure of male rats to Bisphenol A impairs fertility and expression of sertoli cell junctional proteins in the testis

Cited by 221 publications

References 41 publications

Connexin 43 expression in Sprague-Dawley rat seminiferous epithelium afterin uteroexposure to flutamide

Connexin 43 expression in Sprague-Dawley rat seminiferous epithelium afterin uteroexposure to flutamide

Connexin 43 is critical to maintain the homeostasis of the blood–testis barrier via its effects on tight junction reassembly

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

Contact Info

Product

Resources

About