Bisphenol A alters differentiation of Leydig cells in the rabbit fetal testis

The endocrine disruptor Bisphenol A (BPA) crosses the placental barrier and reaches the fetal organs, including the gonads. In the testis, fetal Leydig cells (FLC) produce testosterone required for the male phenotype and homeostatic cell-cell signaling in the developing testis. Although it is known that BPA affects cell proliferation and differentiation in FLC, results concerning the mechanism involved are contradictory, mainly due to differences among species. Fast developing fetal gonads of rodents lack cortex and medulla, whereas species with more extended gestation periods form these two tissue compartments. The rabbit provides a good subject for studying the disruptive effect of BPA in fetal Leydig and possible postnatal endocrine consequences in adult Leydig cells. Here, we investigated the impact of BPA administered to pregnant rabbits does, on the FLC population of the developing testes. Using qRT-PCR, we assessed the levels of SF1, CYP11A1, 3β-HSD, and androgen receptor (AR) genes, and levels of fetal serum testosterone were measured by ELISA. These levels correlated with both the mitotic activity and the ultrastructural differentiation of the FLC by confocal and electron microscopy, respectively. Results indicate that BPA alters the expression levels of essential genes involved in androgen paracrine signaling, modifies the proliferation and differentiation of the FLCs, and alters the levels of serum testosterone after birth. Thus, BPA may change the postnatal levels of serum testosterone due to the impaired FLC population formed by the proliferating stem and non-proliferating cytodifferentiated FLC.

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The Antioxidant Phytochemical Schisandrin A Promotes Neural Cell Proliferation and Differentiation after Ischemic Brain Injury

Molecules ◽

10.3390/molecules26247466 ◽

2021 ◽

Vol 26 (24) ◽

pp. 7466

Author(s):

Wentian Zong ◽

Mostafa Gouda ◽

Enli Cai ◽

Ruofeng Wang ◽

Weijie Xu ◽

...

Keyword(s):

Neural Progenitor Cell ◽

Nerve Fibers ◽

Specific Class ◽

Class Iii ◽

Promoting Effect ◽

Western Blot Assay ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation ◽

Late Recovery ◽

The Impact

Schisandrin A (SCH) is a natural bioactive phytonutrient that belongs to the lignan derivatives found in Schisandra chinensis fruit. This study aims to investigate the impact of SCH on promoting neural progenitor cell (NPC) regeneration for avoiding stroke ischemic injury. The promoting effect of SCH on NPCs was evaluated by photothrombotic model, immunofluorescence, cell line culture of NPCs, and Western blot assay. The results showed that neuron-specific class III beta-tubulin (Tuj1) was positive with Map2 positive nerve fibers in the ischemic area after using SCH. In addition, Nestin and SOX2 positive NPCs were significantly (p < 0.05) increased in the penumbra and core. Further analysis identified that SCH can regulate the expression level of cell division control protein 42 (Cdc42). In conclusion, our findings suggest that SCH enhanced NPCs proliferation and differentiation possible by Cdc42 to regulated cytoskeletal rearrangement and polarization of cells, which provides new hope for the late recovery of stroke.

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Consequences of early postnatal lipopolysaccharide exposure on developing lungs in mice

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00560.2017 ◽

2019 ◽

Vol 316 (1) ◽

pp. L229-L244 ◽

Cited By ~ 7

Author(s):

Amrit Kumar Shrestha ◽

Matthew L. Bettini ◽

Renuka T. Menon ◽

Vashisht Y. N. Gopal ◽

Shixia Huang ◽

...

Keyword(s):

Cell Proliferation ◽

Lung Development ◽

Dependent Manner ◽

T Regulatory Cell ◽

Lung Macrophage ◽

Flow Cytometric ◽

Cell Proliferation And Differentiation ◽

Proliferation And Apoptosis ◽

Proliferation And Differentiation ◽

The Impact

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of infants that is characterized by interrupted lung development. Postnatal sepsis causes BPD, yet the contributory mechanisms are unclear. To address this gap, studies have used lipopolysaccharide (LPS) during the alveolar phase of lung development. However, the lungs of infants who develop BPD are still in the saccular phase of development, and the effects of LPS during this phase are poorly characterized. We hypothesized that chronic LPS exposure during the saccular phase disrupts lung development by mechanisms that promote inflammation and prevent optimal lung development and repair. Wild-type C57BL6J mice were intraperitoneally administered 3, 6, or 10 mg/kg of LPS or a vehicle once daily on postnatal days (PNDs) 3–5. The lungs were collected for proteomic and genomic analyses and flow cytometric detection on PND6. The impact of LPS on lung development, cell proliferation, and apoptosis was determined on PND7. Finally, we determined differences in the LPS effects between the saccular and alveolar lungs. LPS decreased the survival and growth rate and lung development in a dose-dependent manner. These effects were associated with a decreased expression of proteins regulating cell proliferation and differentiation and increased expression of those mediating inflammation. While the lung macrophage population of LPS-treated mice increased, the T-regulatory cell population decreased. Furthermore, LPS-induced inflammatory and apoptotic response and interruption of cell proliferation and alveolarization was greater in alveolar than in saccular lungs. Collectively, the data support our hypothesis and reveal several potential therapeutic targets for sepsis-mediated BPD in infants.

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The Impact of Metallic Nanoparticles on Stem Cell Proliferation and Differentiation

Nanomaterials ◽

10.3390/nano8100761 ◽

2018 ◽

Vol 8 (10) ◽

pp. 761 ◽

Cited By ~ 19

Author(s):

Ahmed Abdal Dayem ◽

Soo Lee ◽

Ssang-Goo Cho

Keyword(s):

Cell Proliferation ◽

Stem Cell ◽

Metallic Nanoparticles ◽

Stem Cell Differentiation ◽

Stem Cell Proliferation ◽

Cell Functions ◽

Cell Proliferation And Differentiation ◽

Wide Range ◽

Proliferation And Differentiation ◽

The Impact

Nanotechnology has a wide range of medical and industrial applications. The impact of metallic nanoparticles (NPs) on the proliferation and differentiation of normal, cancer, and stem cells is well-studied. The preparation of NPs, along with their physicochemical properties, is related to their biological function. Interestingly, various mechanisms are implicated in metallic NP-induced cellular proliferation and differentiation, such as modulation of signaling pathways, generation of reactive oxygen species, and regulation of various transcription factors. In this review, we will shed light on the biomedical application of metallic NPs and the interaction between NPs and the cellular components. The in vitro and in vivo influence of metallic NPs on stem cell differentiation and proliferation, as well as the mechanisms behind potential toxicity, will be explored. A better understanding of the limitations related to the application of metallic NPs on stem cell proliferation and differentiation will afford clues for optimal design and preparation of metallic NPs for the modulation of stem cell functions and for clinical application in regenerative medicine.

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ADP-ribosylation signalling and human disease

Open Biology ◽

10.1098/rsob.190041 ◽

2019 ◽

Vol 9 (4) ◽

pp. 190041 ◽

Cited By ~ 11

Author(s):

Luca Palazzo ◽

Petra Mikolčević ◽

Andreja Mikoč ◽

Ivan Ahel

Keyword(s):

Neurological Disorders ◽

Fine Tuning ◽

Molecular Medicine ◽

Biological Processes ◽

Post Translational Modification ◽

Adp Ribosylation ◽

Damage Repair ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation ◽

The Impact

ADP-ribosylation (ADPr) is a reversible post-translational modification of proteins, which controls major cellular and biological processes, including DNA damage repair, cell proliferation and differentiation, metabolism, stress and immune responses. In order to maintain the cellular homeostasis, diverse ADP-ribosyl transferases and hydrolases are involved in the fine-tuning of ADPr systems. The control of ADPr network is vital, and dysregulation of enzymes involved in the regulation of ADPr signalling has been linked to a number of inherited and acquired human diseases, such as several neurological disorders and in cancer. Conversely, the therapeutic manipulation of ADPr has been shown to ameliorate several disorders in both human and animal models. These include cardiovascular, inflammatory, autoimmune and neurological disorders. Herein, we summarize the recent findings in the field of ADPr, which support the impact of this modification in human pathophysiology and highlight the curative potential of targeting ADPr for translational and molecular medicine.

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Impact of Vitamin D on Physical Efficiency and Exercise Performance—A Review

Nutrients ◽

10.3390/nu11112826 ◽

2019 ◽

Vol 11 (11) ◽

pp. 2826 ◽

Cited By ~ 5

Author(s):

Michał Wiciński ◽

Dawid Adamkiewicz ◽

Monika Adamkiewicz ◽

Maciej Śniegocki ◽

Marta Podhorecka ◽

...

Keyword(s):

Vitamin D ◽

Exercise Performance ◽

Strong Relationship ◽

High Quality Research ◽

Vitamin D Receptors ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation ◽

Strongly Connected ◽

The Impact

Vitamin D deficiency amongst athletes and the general population seems to be a prominent problem. The most recognized role of vitamin D is its regulation of calcium homeostasis; there is a strong relationship between vitamin D and bone health. Moreover, its concentrations are associated with muscle function and immune response in both the general and athletic populations. Vitamin D level is strongly connected with the presence of VDRs (vitamin D receptors) in most human extraskeletal cells. Expression of multiple myogenic transcription factors enhancing muscle cell proliferation and differentiation is caused by an exposure of skeletal muscles to vitamin D. The aim of this review is to summarize current understanding of the significance of vitamin D on exercise performance and physical efficiency, as well to analyze the impact of vitamin D on multiple potential mechanisms. More high-quality research studies, considering free 25(OH)D as a better marker of vitamin D status, the baseline level of 25(OH)D and multiple pathways of vitamin D acting and usage in athletes are required.

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Defects of Prostate Development and Reproductive System in the Estrogen Receptor-α Null Male Mice

Endocrinology ◽

10.1210/en.2008-0044 ◽

2008 ◽

Vol 150 (1) ◽

pp. 251-259 ◽

Cited By ~ 50

Author(s):

Ming Chen ◽

Iawen Hsu ◽

Andrew Wolfe ◽

Sally Radovick ◽

KuoHsiang Huang ◽

...

Keyword(s):

Estrogen Receptor ◽

Reproductive System ◽

Serum Testosterone ◽

Branching Morphogenesis ◽

Estrogen Receptor Α ◽

Seminiferous Tubules ◽

Male Mice ◽

Stromal Compartment ◽

Proliferation And Differentiation ◽

The Impact

The estrogen receptor-α knockout (ERαKO, ERα−/−) mice were generated via the Cre-loxP system by mating floxed ERα mice with β-actin (ACTB)-Cre mice. The impact of ERα gene deletion in the male reproductive system was investigated. The ACTB-Cre/ERα−/− male mice are infertile and have lost 90% of epididymal sperm when compared with wild-type mice. Serum testosterone levels in ACTB-Cre/ERα−/− male mice are 2-fold elevated. The ACTB-Cre/ERα−/− testes consist of atrophic and degenerating seminiferous tubules with less cellularity in the disorganized seminiferous epithelia. Furthermore, the ventral and dorsal-lateral prostates of ACTB-Cre/ERα−/− mice display reduced branching morphogenesis. Loss of ERα could also be responsible for the decreased fibroblast proliferation and changes in the stromal content. In addition, we found bone morphogenetic protein, a mesenchymal inhibitor of prostatic branching morphogenesis, is significantly up-regulated in the ACTB-Cre/ERα−/− prostates. Collectively, these results suggest that ERα is required for male fertility, acts through a paracrine mechanism to regulate prostatic branching morphogenesis, and is involved in the proliferation and differentiation of prostatic stromal compartment. Newly generated ACTB-Cre/Estrogen receptor alpha knockout (ERα-/-) male mice show that ERα acts through a paracrine mechanism to regulate prostatic branching morphogenesis and is involved in the proliferation and differentiation of prostatic stoma.

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Fsh and Lh have common and distinct effects on gene expression in rainbow trout testis

Journal of Molecular Endocrinology ◽

10.1530/jme-12-0197 ◽

2012 ◽

Vol 50 (1) ◽

pp. 1-18 ◽

Cited By ~ 38

Author(s):

Elisabeth Sambroni ◽

Antoine D Rolland ◽

Jean-Jacques Lareyre ◽

Florence Le Gac

Keyword(s):

Cell Fate ◽

Leydig Cells ◽

Wnt Pathway ◽

Mammalian Species ◽

Testicular Cell ◽

Paracrine Factors ◽

Regulatory Pathways ◽

Cell Proliferation And Differentiation ◽

General Rules ◽

Proliferation And Differentiation

The general rules established from mammalian species for the regulation of spermatogenesis by gonadotropins may not be fully relevant in fish. Particularly, Fsh is as potent as Lh to stimulate steroidogenesis and the Fsh receptor is expressed in Leydig cells. In seasonal breeders, Fsh is likely the major gonadotropin involved in spermatogenesis onset and Lh is required to support spermatogenesis progression and gamete release. However, the genes that relay the action of Fsh and Lh have been poorly investigated in fish. The present study was aimed at identifying gonadotropin-dependent genes expressed in the testis during fish puberty. We cultured pubertal trout testicular explants for 96 h, with or without gonadotropin, and analyzed transcriptome variations using microarrays. Fsh and Lh had similar effects on a large group of genes while other genes were preferentially regulated by one or the other gonadotropin. We showed that most of the responsive genes were expressed in somatic cells and exhibited relevant patterns during the seasonal reproductive cycle. Some genes preferentially modulated by Lh could be involved in testicular cell fate (pvrl1andbty) or sperm maturation (ehmt2andracgap1) and will deserve further examination. Besides Fsh's effects on the steroidogenic pathway, our study demonstrates that Fsh coordinates relevant stimulatory and inhibitory paracrine factors known to regulate early germ cell proliferation and differentiation. Some of these genes belong to major regulatory pathways including the Igf pathway (igf1b/igf3andigfbp6), the Tgfb pathway (amh,inha,inhba, andfstl3), the Wnt pathway (wisp1), and pleiotrophin (mdka).

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