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

Rode, Kristina; Weider, Karola; Damm, Oliver; Wistuba, Joachim; Langeheine, Marion; Brehm, Ralph

doi:10.1016/j.repbio.2018.08.001

Cited by 24 publications

(23 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Regarding this hypothesis, over-expression of the SC-derived factor GDNF has been reported to inhibit germ cell differentiation, resulting in an accumulation of undifferentiated spermatogonia [139], hence supporting our hypothesis, as SCCx43KO mice exhibit a spermatogenic arrest at the level of undifferentiated spermatogonia [93].…”

Section: Discussionsupporting

confidence: 85%

“…Stra8/STRA8 expression has previously been examined in prepubertal and adult SCCx43KO mice in comparison with their WT littermates and found to be altered or absent [9,93]. NGS data of the present study revealed a significant downregulation of Stra8 in 8-, 10-, and 12-day-old SCCx43KO mice compared to their WT littermates.…”

Section: Discussionsupporting

confidence: 53%

“…Additionally, testicular samples of adult KO and WT mice were immunostained for LIN28A and SALL4 ( Figure 10). According to the previous study [93], remaining GCs in seminiferous tubules of adult SCCx43KO mice were identified as undifferentiated spermatogonia. Thus, prepubertal SCCx43KO mice seem to have significantly reduced transcript levels of Lin28 and Sall4 but still a sufficient amount of these for translation into detectable protein volumes.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, to clearly distinguish between GCs and SCs in the present study, SOX9 IHC was used to mark SC nuclei and then to determine intratubular cell numbers revealing reduced GC numbers in KO mice pursuant to recent findings [9,93]. However, in contrast to Giese et al [9], increased SC numbers per seminiferous tubule have already been detected in 8-day-old KO mice and become more evident in 10-and 12-day-old KO animals (Figure 3), implying an enhanced SC proliferation already at this stage.…”

Section: Discussionmentioning

confidence: 99%

“…Rode and colleagues [93] reported that during puberty, the GC component of SCCx43KO mice comprised for the most part undifferentiated spermatogonia and that in adult KO animals, spermatogenesis is arrested at the level of undifferentiated spermatogonia, observed alterations in gene expression may indicate that loss of Cx43 in SCs already influences a subpopulation of undifferentiated spermatogonia. However, apart from the different GC numbers, no obvious differences could be detected for LIN28A and SALL4 expression on protein level between the KO mice and their WT littermates.…”

Section: Discussionmentioning

confidence: 99%

See 4 more Smart Citations

Loss of Cx43 in Murine Sertoli Cells Leads to Altered Prepubertal Sertoli Cell Maturation and Impairment of the Mitosis-Meiosis Switch

Hilbold

Distl

Hoedemaker

et al. 2020

Cells

Self Cite

View full text Add to dashboard Cite

Male factor infertility is a problem in today’s society but many underlying causes are still unknown. The generation of a conditional Sertoli cell (SC)-specific connexin 43 (Cx43) knockout mouse line (SCCx43KO) has provided a translational model. Expression of the gap junction protein Cx43 between adjacent SCs as well as between SCs and germ cells (GCs) is known to be essential for the initiation and maintenance of spermatogenesis in different species and men. Adult SCCx43KO males show altered spermatogenesis and are infertile. Thus, the present study aims to identify molecular mechanisms leading to testicular alterations in prepubertal SCCx43KO mice. Transcriptome analysis of 8-, 10- and 12-day-old mice was performed by next-generation sequencing (NGS). Additionally, candidate genes were examined by qRT-PCR and immunohistochemistry. NGS revealed many significantly differentially expressed genes in the SCCx43KO mice. For example, GC-specific genes were mostly downregulated and found to be involved in meiosis and spermatogonial differentiation (e.g., Dmrtb1, Sohlh1). In contrast, SC-specific genes implicated in SC maturation and proliferation were mostly upregulated (e.g., Amh, Fshr). In conclusion, Cx43 in SCs appears to be required for normal progression of the first wave of spermatogenesis, especially for the mitosis-meiosis switch, and also for the regulation of prepubertal SC maturation.

show abstract

Section: Discussionsupporting

confidence: 85%

Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Loss of Cx43 in Murine Sertoli Cells Leads to Altered Prepubertal Sertoli Cell Maturation and Impairment of the Mitosis-Meiosis Switch

Hilbold

Distl

Hoedemaker

et al. 2020

Cells

Self Cite

View full text Add to dashboard Cite

show abstract

Benzophenone‐3 breaches mouse Sertoli cell barrier and alters F‐actin organization without evoking apoptosis

Jiao

Chen

et al. 2021

Environmental Toxicology

View full text Add to dashboard Cite

Benzophenone‐3 (BP‐3), one of the most commonly utilized ultraviolet filters in personal care products, has aroused public concern in recent years for its high chances of human exposure. Previous studies have found that BP‐3 can impair testes development and spermatogenesis, but the targets of BP‐3 are still unknown. In this study, primary Sertoli cells from 20‐day‐old mice were treated in vitro with 0–100 μM BP‐3 for 24 h to identify its toxicity on Sertoli cells and Sertoli cell barrier. Results demonstrated that BP‐3 could induce a notable change in cell morphology and impair Sertoli cell viability. The analysis of transepithelial electrical resistance showed that the integrity of the Sertoli cell barrier was destroyed by BP‐3 (100 μM). Some structural proteins of the barrier including ZO‐1, Occludin, and Connexin43 were lower expressed and the localization of basal ectoplasmic specializations protein β‐catenin was altered because of BP‐3 treatment. Further exploration suggested that BP‐3 led to Sertoli cell F‐actin disorganization by affecting the expression of Rictor, a key component of the mTORC2 complex. Moreover, although increased DNA damage marker γH2A.X was observed in the treatment group, the cell apoptosis rate was changeless which was further confirmed by increased BAX and stable Bcl‐2 (two primary apoptosis regulating proteins). In conclusion, this study revealed that BP‐3 had the potential to perturb the Sertoli cell barrier through altered junction proteins and disorganized F‐actin, but it could hardly evoke Sertoli cell apoptosis.

show abstract

Physiology of Testicular Function

Wistuba,

Neuhaus,

Nieschlag

2023

Andrology

View full text Add to dashboard Cite

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

Cited by 24 publications

References 59 publications

Loss of Cx43 in Murine Sertoli Cells Leads to Altered Prepubertal Sertoli Cell Maturation and Impairment of the Mitosis-Meiosis Switch

Loss of Cx43 in Murine Sertoli Cells Leads to Altered Prepubertal Sertoli Cell Maturation and Impairment of the Mitosis-Meiosis Switch

Benzophenone‐3 breaches mouse Sertoli cell barrier and alters F‐actin organization without evoking apoptosis

Physiology of Testicular Function

Contact Info

Product

Resources

About