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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The growth, differentiation, and death/survival of spermatogonia are precisely regulated for the proper production of spermatozoa. We have previously shown that Bcl-2 ectopically expressed in spermatogonia caused the inhibition of normal spermatogonial apoptosis and the subsequent failure of differentiation in transgenic mice. In addition, the growth of spermatogonial stem cells seemed to be temporally arrested in the transgenic mice. In the present study, we attempted to examine whether the abnormality of spermatogonia described above was caused by Bcl-2 misexpression in the spermatogonia or by an abnormal spermatogenic environment of the transgenic mice. We transplanted testicular cells of transgenic mice to seminiferous tubules of W/Wv mice in which transplanted normal testicular cells can undergo spermatogenesis. We found that the transplanted spermatogonia of the transgenic mice reproduced a series of abnormal changes including temporal growth arrest of spermatogonial stem cells and abnormal accumulation of spermatogonia in tubules, which were also observed in the testes of the transgenic mice. The results indicated that Bcl-2 inhibited apoptosis of spermatogonia and growth of spermatogonial stem cells in a cell-intrinsic manner. We also cultured testicular cells of transgenic mice and found that the spermatogonia of the transgenic mice were better able to survive than were those of wild-type mice but that their differentiation was not affected. The result suggested that failure of differentiation of the accumulated spermatogonia in the transgenic testes is not due to the abnormality of the bcl-2 misexpressing spermatogonia, but may be caused by extrinsic problems including improper interaction of spermatogonia with supporting cells.
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PMID:Bcl-2 inhibits apoptosis of spermatogonia and growth of spermatogonial stem cells in a cell-intrinsic manner. 1114 12

Studies into the mechanisms underlying spermatogenesis, the process by which spermatogonia undergo meiosis to become spermatozoa, have identified a number of genetic determinants of male infertility. Indeed, a more comprehensive knowledge of the genetic regulation of spermatogenesis has alleviated the dependence on the use of idiopathic infertility as a classification for sterile men for whom a cause for their infertility is unknown, as genetic factors become more accountable for this phenotype. This review focuses on selected areas implicated in male infertility including: (i) autosomal and sex chromosomal abnormalities; (ii) genetic disorders associated with impaired gonadotrophin secretion or action; (iii) microdeletions within regions of the Y-chromosome containing candidate gene families for spermatogenesis; (iv) the genetic nexus between cystic fibrosis and congenital bilateral absence of the vas deferens; and (v) insights into human infertility as gleaned from animal studies into mechanisms involving the Bcl-2 family of apoptosis regulators and the interaction between the c-kit encoded tyrosine kinase receptor and its ligand, stem cell factor. As significant advances continue to further knowledge of the genetic basis of male infertility, such as those leading to an understanding of the aforementioned areas, greater progress can be made to rectify or at least ameliorate social stigmas associated with sterility.
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PMID:Selected genetic factors associated with male infertility. 1209 33

Human and animal models have evidenced how estrogen insufficiency is associated with abnormal spermatogenesis and male infertility. We previously demonstrated that estradiol is able to influence both capacitation and acrosome reaction in human ejaculated spermatozoa. It remains to be elucidated whether the biochemical changes induced by estradiol, in a rapid nongenomic way, are mediated by a single estrogen receptor (ER) or by the two ER subtypes, ER alpha and ER beta. In the present study, we have first demonstrated the concomitant expression of ER beta and ER alpha in human ejaculated spermatozoa. By RT-PCR and Southern blot, transcripts of both ERs were detected. Western blot analysis showed ER alpha and ER beta proteins at the same size as the "classical" ERs. The localization of ER alpha and ER beta with the immunocytochemistry shows a differential distribution of the two ER subtypes, the former being prevalently located in the midpiece, but the latter being in the tail. Estradiol has been associated with sperm longevity; however, the mechanism through which estradiol acts in sperm survival was never investigated. Upon estradiol exposure, we observed an enhanced phosphorylation of the proteins involved in the phosphatidylinositol-3-OH kinase (PI3K)/Akt pathway like PDK1, Akt, GSK-3, Bcl-2, together with ERK1/2, which was also involved in cell survival signals. Moreover, such phosphorylations were reduced in the presence of ICI 182, 780, addressing the role of estradiol and ERs in sperm survival. For instance we have provided, for the first time, a different interaction of the two ERs with the PI3K/Akt pathway, because ER alpha interacts with the p55 regulatory subunit of PI3K, whereas ER beta interacts with Akt1. However, it still remains to be elucidated whether the functional role of each of the ER subtypes in sperm survival signaling is redundant or distinct.
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PMID:Estrogen receptor (ER)alpha and ER beta are both expressed in human ejaculated spermatozoa: evidence of their direct interaction with phosphatidylinositol-3-OH kinase/Akt pathway. 1500 46

The BH3-only proteins of the Bcl-2 family initiate apoptosis through the activation of Bax-like relatives. Loss of individual BH3-only proteins can lead either to no phenotype, as in mice lacking Bik, or to marked cell excess, as in the hematopoietic compartment of animals lacking Bim. To investigate whether functional redundancy with Bim might obscure a significant role for Bik, we generated mice lacking both genes. The hematopoietic compartments of bik-/-bim-/- and bim-/- mice were indistinguishable. However, although testes develop normally in mice lacking either Bik or Bim, adult bik-/-bim-/- males were infertile, with reduced testicular cellularity and no spermatozoa. The testis of young bik-/-bim-/- males, like those lacking Bax, exhibited increased numbers of spermatogonia and spermatocytes, although loss of Bik plus Bim blocked spermatogenesis somewhat later than Bax deficiency. The initial excess of early germ cells suggests that spermatogenesis fails because supporting Sertoli cells are overwhelmed. Thus, Bik and Bim share, upstream of Bax, the role of eliminating supernumerary germ cells during the first wave of spermatogenesis, a process vital for normal testicular development.
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PMID:Concomitant loss of proapoptotic BH3-only Bcl-2 antagonists Bik and Bim arrests spermatogenesis. 1627 31

Apoptosis is a process of cell suicide, the mechanisms of which are encoded in the chromosomes of all nucleated cells. Apoptosis occurs spontaneously throughout mammalian spermatogenesis for the development of normal mature spermatozoa and for the elimination of excess or abnormal germ cells: a critical prerequisite for functional spermatogenesis under physiological conditions. Any deregulation of the apoptotic process during spermatogenesis would lead to defective sperm formation and while increased apoptosis could potentially lead to infertility, decreased cell death could do the same by disrupting testicular homeostasis due to accumulation of cells. Male germ cell apoptosis occurs through two major pathways, involving either mitochondria (intrinsic) or cell surface death receptors (extrinsic). The mitochondrial pathway of apoptosis involves the Bcl-2 group of proteins and different members of this group are involved in diverse situations. The cell death receptor pathway involves members of the TNF receptor superfamily. The stimuli for germ cell apoptosis are internal cues that control proper homeostasis of the testicular tissue or external agents including testicular toxins, heat stress and chemotherapeutic agents. In addition, an imbalance of hormones can lead to the apoptosis of germ cells. The pathway of apoptosis adopted by the germ cells depends on the type of stimuli they receive. This review discusses the recent advances made in the understanding of the mechanisms of germ cell apoptosis that may provide clues to the control of male fertility or treating germ cell tumors and other testis associated pathological conditions.
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PMID:Modulators of spermatogenic cell survival. 1756 72

Normal testicular function is dependent upon hormones acting through endocrine and paracrine pathways both in vivo and in vitro. Sertoli cells provide factors necessary for the successful progression of spermatogonia into spermatozoa. Sertoli cells have receptors for follicle stimulating hormone (FSH) and testosterone which are the main hormonal regulators of spermatogenesis. Hormones such as testosterone, FSH and luteinizing hormone (LH) are known to influence the germ cell fate. Their removal induces germ cell apoptosis. Proteins of the Bcl-2 family provide one signaling pathway which appears to be essential for male germ cell homeostasis. In addition to paracrine signals, germ cells also depend upon signals derived from Sertoli by direct membrane contact. Somatostatin is a regulatory peptide playing a role in the regulation of the proliferation of the male gametes. Activin A, follistatin and FSH play a role in germ cell maturation during the period when gonocytes resume mitosis to form the spermatogonial stem cells and differentiating germ cell populations. In vitro cultures systems have provided evidence that spermatogonia in advance stage of differentiation have specific regulatory mechanisms that control their fate. This review article provides an overview of the literature concerning the hormonal pathways regulating spermatogenesis.
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PMID:Hormonal regulation of spermatogenesis and spermiogenesis. 1840 Apr 89

We studied the effects of toxins, which inhibited the motility of boar spermatozoa, on rat liver mitochondria. The toxins studied were originally from bacteria isolated from moisture-damaged buildings where inhabitants exhibited symptoms, or from food causing poisoning. Some strains of Bacillus cereus and Streptomyces griseus produced potassium ionophoric peptides cereulide and valinomycin (Mikkola, et al., European Journal of Biochemistry 1999; 263: 112-117). Of interest is that channels were formed in black-lipid membranes (BLM) with a selectivity of K(+) > Na(+) at a concentration of 26 nM. Recently, bafilomycin A1--an inhibitor of V-H(+)ATPases--was found also to be a K(+)-specific ionophore active at nanomolar concentrations (Teplova, et al., J Bioenerg Biomembr 2007; 39: 321-329), while B. amyloliquefaciens produced amylosin, a cation channel-forming peptide with a higher selectivity for K(+) over Na(+) at around 200 nM concentrations (Mikkola, et al., Toxicon 2007; 49: 1158-1171). Of interest is that channels were formed in BLM with a selectivity of K(+) > Na(+) at a concentration of 26 nM. The ionophores and the channel-forming amylosin caused swelling of energized mitochondria due to uptake of K(+), loss of membrane potential, inhibition of maximal respiration rates due to loss of pyridine nucleotides, and inhibition of ATP synthesis. Various cell types may have different sensitivities to the effects of the ionophores. Thus, the mitochondrial membrane potential in neuronal cells was more sensitive to cereulide than in differentiated Paju cells (Teplova, et al., Acta Biochimica Polonica 2004; 51: 539-544). Swelling causes release of proapoptotic factors from mitochondria, which explains that undifferentiated neuronal cells were sensitive, while differentiated Paju cells were resistant, which probably is due to them having an increased expression of the antiapoptotic protein Bcl-2 and the neuroprotective stanniocalcin.
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PMID:Microbial toxin's effect on mitochondrial survival by increasing K+ uptake. 1973 54

The present study was conducted to investigate the possible protective effects of lycopene (LP) and ellagic acid (EA) on aroclor (AR) 1254-induced testicular and spermatozoal toxicity associated with the oxidative stress and apoptosis in male rats. The control group was treated with placebo. LP (10 mg/kg/every other day), EA (2 mg/kg/every other day) and AR (2 mg/kg/day) groups were given alone LP, EA and AR respectively. One of the last two groups received AR + LP, and the other treated with AR + EA. Body and reproductive organ weights, epididymal sperm characteristics, testicular tissue lipid peroxidation levels, antioxidant enzyme activities, histopathological changes and apoptosis via Bax and Bcl-2 genes were investigated. AR administration caused statistically significant decreases in body-weight, epididymal sperm concentration, testicular superoxide dismutase activity, diameters of seminiferous tubules, germinal cell layer thickness and Johnsen's testicular score, and increases in relative weights of testis, epidydimis and seminal vesicles, rates of abnormal sperm and apoptotic cell expression along with degeneration, desquamation and disorganization in spermatogenic cells, and interstitial oedema and congestion in testicular tissue. LP and EA treatments to AR-treated rats markedly decreased abnormal sperm rates, testicular thiobarbituric acid reactive substances level, and increased the glutathione (GSH) level, GSH-peroxidase, catalase activities and epidiymal sperm concentration as compared with the alone AR group. Additionally, the AR-induced histopathological damages were totally or partially recovered by LP or EA administrations respectively. AR damages the testicular tissue and spermatozoa by impairing the oxidant/antioxidant balance and by increasing the apoptotic spermatogenic cell rates. However, both LP and EA have modulator effects on AR-induced reproductive dysfunction in male rats.
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PMID:Modulatory effects of lycopene and ellagic acid on reproductive dysfunction induced by polychlorinated biphenyl (Aroclor 1254) in male rats. 2007 68

Artificial insemination (AI) with post-thawed boar spermatozoa results in low farrowing rates and reduced litter sizes mainly due to cryoinjury or damages to spermatozoa during cryopreservation. Low viability and motility of post-thawed boar spermatozoa are highly associated with apoptosis during cryopreservation. Although glycerol is widely used a cryoprotectant (CPA) for boar spermatozoa cryopreservation, the mechanism and relationship between glycerol and apoptosis-related gene expression needs to be clarified. In this study, we treated boar spermatozoa with different concentrations of glycerol in lactose egg yolk (LEY) extender to evaluate the apoptosis-related gene expression and protease activities of caspases. These results show that: (1) low concentrations of glycerol (2% and 3%) were more suitable for boar spermatozoa cryopreservation; (2) apoptosis-related genes involved in intrinsic mitochondrial and extrinsic death receptor apoptotic signaling pathways were widely expressed in different concentrations of glycerol treated boar spermatozoa; (3) there was a significant positive correlation (r=0.840, P=0.037) between the percentage of Annexin V(+)/PI(+) staining spermatozoa and caspase-6/9 protease activity. In conclusion, 2% and 3% glycerol have the best anti-apoptotic effects, and the expression of Fas/FasL and Bcl-2/Bax have a strong correlation with spermatozoa parameters.
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PMID:Effects of glycerol on apoptotic signaling pathways during boar spermatozoa cryopreservation. 2468 Aug 61

The effects of quinestrol on spermatogenesis were investigated in adult male mice by daily intragastric administration of quinestrol with various doses of 5, 10, 50 and 100mg/kg body weight for 10 days. The sperm counts declined while the number of abnormal spermatozoa went up in mice treated with quinestrol. The testicular weight and seminiferous tubular area gradually declined with increasing dosages of quinestrol to 50 and 100mg/kg. Rarefied germ cells showed irregular distributions in the seminiferous tubules of mice treated with 50 and 100mg/kg quinestrol. Apoptosis was highly pronounced in spermatogonia, spermatocytes, spermatids and Leydig cells. Antioxidant enzyme activities - superoxide dismutase and glutathione peroxidase - as well as total antioxidant capacity significantly reduced, while malondialdehyde contents increased. The number of germ cells expressing caspase-3, p53, Bax and FasL significantly increased whereas cells expressing Bcl-2 significantly decreased in groups treated with 50 and 100mg/kg quinestrol compared with the control. The concentration of nitrogen monoxidum also increased significantly under these dosages. The results suggest that quinestrol stimulates oxidative stress to induce apoptosis in spermatogenic cells through the mitochondrial and death receptor pathways in adult male mice.
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PMID:Quinestrol induces spermatogenic apoptosis in vivo via increasing pro-apoptotic proteins in adult male mice. 2503 89


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