The aim of the study was to examine the potential impacts of bisphenol A (BPA) and its analogues BPB, BPF, and BPS on mice TM3 Leydig cells, with respect to basal cell viability parameters such as metabolic activity, cell membrane integrity, and lysosomal activity after 48-h exposure. In addition, monitoring of potential bisphenol´s actions included evaluation of ROS production and gap junctional intercellular communication (GJIC) complemented by determination of testosterone secretion. Obtained results revealed significant inhibition in mitochondrial activity started at 10 microg/ml of bisphenols after 48-h exposure. Cell membrane integrity was significantly decreased at 5 microg/ml of BPA and BPF and 10, 25, and 50 microg/ml of BPA and BPS. The lysosomal activity was significantly affected at 10, 25, and 50 microg/ml of applied bisphenols. A significant overproduction of ROS was recorded mainly at 5 and 10 microg/ml of tested compounds. In addition, significant inhibition of GJIC was observed at 5 microg/ml of BPB followed by a progressive decline at higher applied doses. In the case of testosterone production, a significant decline was confirmed at 10, 25 and 50 microg/ml.

• MeSH
• benzhydrylové sloučeniny metabolismus   MeSH
• endokrinní disruptory * farmakologie   MeSH
• Leydigovy buňky * MeSH
• myši MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• sulfony farmakologie   MeSH
• testosteron metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• benzhydrylové sloučeniny MeSH
• bisphenol A MeSH Prohlížeč
• endokrinní disruptory * MeSH
• reaktivní formy kyslíku MeSH
• sulfony MeSH
• testosteron MeSH

Male reproductive functions are an important area affecting men´s overall health and well-being. However, during the last years, there has been observed increasing incidence of male reproductive issues. The radical growth has been recorded parallelly with a massive expanse of industrialization and agricultural chemigation. Many groups of experts have begun to identify several potential factors and substances that may have adverse effects on men´s reproductive health. Since then, xenobiotics have become a major concern of many scientific studies. There is evidence that most of them have multigenerational and transgenerational effects on reproductive health, which is a serious problem for our population. Bisphenol A could be considered as one of the most studied endocrine disruptors. Until now, several negative effects of bisphenol A were associated with reduced weight testes, histological alterations, impairment spermatogenesis, and steroidogenesis as well as with testes or prostate cancer. Due to convincing evidence, bisphenol A has been started to replace by its analogues such as bisphenol B, S, F, in order to eliminate and suppress the risk of exposure to bisphenol A. However, it seems that a lack of toxicological analyses allows using of these hazardous substances in daily life. Their harmful effect was confirmed by the animal in vitro and in vivo models, while the epidemiological studies monitoring the impact of bisphenol analogues on men's reproductive health are markedly limited. This review provides information about the effects of bisphenol on reproductive health in men. At the same time, it is focused on physiological aspects of sperm viability, steroid hormone secretion, sperm motility, or testes histology in relation to bisphenols exposure.

• MeSH
• benzhydrylové sloučeniny toxicita   MeSH
• endokrinní disruptory * toxicita   MeSH
• fenoly MeSH
• lidé MeSH
• motilita spermií * MeSH
• spermatogeneze MeSH
• testis MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• benzhydrylové sloučeniny MeSH
• bisphenol A MeSH Prohlížeč
• endokrinní disruptory * MeSH
• fenoly MeSH

Cancer is a complex, multifactorial disease that modern medicine ultimately aims to overcome. Downstream of tyrosine kinase 2 (DOK2) is a well-known tumor suppressor gene, and a member of the downstream protein DOK family of tyrosine kinases. Through a search of original literature indexed in PubMed and other databases, the present review aims to extricate the mechanisms by which DOK2 acts on cancer, thereby identifying more reliable and effective therapeutic targets to promote enhanced methods of cancer prevention and treatment. The review focuses on the role of DOK2 in multiple tumor types in the lungs, intestines, liver, and breast. Additionally, we discuss the potential mechanisms of action of DOK2 and the downstream consequences via the Ras/MPAK/ERK or PI3K/AKT/mTOR signaling pathways.

• MeSH
• adaptorové proteiny signální transdukční genetika   metabolismus   MeSH
• fosfoproteiny genetika   metabolismus   MeSH
• lidé MeSH
• nádory genetika   metabolismus   MeSH
• tumor supresorové geny * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• adaptorové proteiny signální transdukční MeSH
• DOK2 protein, human MeSH Prohlížeč
• Dok2 protein, mouse MeSH Prohlížeč
• fosfoproteiny MeSH

Several plants have the potential to protect essential reproductive processes such as spermatogenesis or steroidogenesis, however, effective concentrations and main mechanisms of action are still unknown. This in vitro study was aimed to assess the effects of Apium graveolens L., Levisticum officinale, and Calendula officinalis L. extracts on the structural integrity, functional activity and gap junctional intercellular communication (GJIC) in mice Leydig cells. TM3 cells were grown in the presence of experimental extracts (37.5; 75; 150 and 300 µg/ml) for 24 h. For the present study, high-performance liquid chromatography analysis was used to quantify flavonoids or phenolic acids. Subsequently, Leydig cell viability was assessed by alamarBlue assay, while the cell membrane integrity was detected by 5-carboxyfluorescein diacetate-acetoxymethyl ester. The level of steroid hormones production was determined by enzyme-linked immunosorbent assay. Additionally, GJIC was assessed by scalpel loading/dye transfer assay. According to our results, Apium graveolens L. significantly increased the viability and cell membrane integrity at 75 µg/ml (109.0±4.3%) followed by a decline at 300 µg/ml (89.4±2.3%). In case of Levisticum officinale and Calendula officinalis L. was observed significant decrease at 150 µg/ml (88.8±11.66%; 87.4±6.0%) and 300 µg/ml (86.2±9.3%; 84.1±4.6%). Furthermore, Apium graveolens L. significantly increased the progesterone and testosterone production (75 and 150 µg/ml) however, Levisticum officinale and Calendula officinalis L. significantly reduced steroid hormones synthesis at 150 and 300 µg/ml. Finally, the disturbance of GJIC was significantly affected at 300 µg/ml of Levisticum officinale (82.5±7.7%) and Calendula officinalis L. (79.8±7.0%). The balanced concentration ratio may support the Leydig cell function, steroidogenesis as well as all essential parameters that may significantly improve reproductive functions.

• MeSH
• Apium * chemie   MeSH
• buněčná membrána účinky léků   patologie   MeSH
• buněčné linie MeSH
• Leydigovy buňky účinky léků   metabolismus   patologie   MeSH
• libeček * chemie   MeSH
• měsíček * chemie   MeSH
• mezerový spoj účinky léků   metabolismus   patologie   MeSH
• mezibuněčná komunikace účinky léků   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• pohlavní steroidní hormony biosyntéza   MeSH
• rostlinné extrakty izolace a purifikace   farmakologie   MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• pohlavní steroidní hormony MeSH
• rostlinné extrakty MeSH

Nickel is a ubiquitous environmental pollutant, which has various effects on reproductive endocrinology. In this study, human adrenocortical carcinoma (NCI-H295R) cell line was used as an in vitro biological model to study the effect of nickel chloride (NiCl2) on the viability and steroidogenesis. The cells were exposed to different concentrations (3.90; 7.80; 15.60; 31.20; 62.50; 125; 250 and 500 microM) of NiCl2 and compared with control group (culture medium without NiCl2). The cell viability was measured by the metabolic activity assay. Production of sexual steroid hormones was quantified by enzyme linked immunosorbent assay. Following 48 h culture of the cells in the presence of NiCl2 a dose-dependent depletion of progesterone release was observed even at the lower concentrations. In fact, lower levels of progesterone were detected in groups with higher doses (>/=125 microM) of NiCl2 (P<0.01), which also elicited cytotoxic action. A more prominent decrease in testosterone production (P<0.01) was also noted in comparison to that of progesterone. On the other hand, the release of 17beta-estradiol was substantially increased at low concentrations (3.90 to 62.50 microM) of NiCl2. The cell viability remained relatively unaltered up to 125 microM (P>0.05) and slightly decreased from 250 microM of NiCl2 (P<0.05). Our results indicate endocrine disruptive effect of NiCl2 on the release of progesterone and testosterone in the NCI-H295R cell line. Although no detrimental effect of NiCl2 (

• MeSH
• adrenokortikální karcinom metabolismus   patologie   MeSH
• adrenokortikální nádory metabolismus   patologie   MeSH
• endokrinní disruptory farmakologie   MeSH
• estradiol metabolismus   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nikl farmakologie   MeSH
• progesteron metabolismus   MeSH
• techniky in vitro MeSH
• testosteron metabolismus   MeSH
• viabilita buněk MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• endokrinní disruptory MeSH
• estradiol MeSH
• nikl MeSH
• progesteron MeSH
• testosteron MeSH

Anthropogenic environmental pollutants affect many physiological, biochemical, and endocrine actions as reproduction, metabolism, immunity, behavior and as such can interfere with any aspect of hormone action. Microbiota and their genes, microbiome, a large body of microorganisms, first of all bacteria and co-existing in the host´s gut, are now believed to be autonomous endocrine organ, participating at overall endocrine, neuroendocrine and immunoendocrine regulations. While an extensive literature is available on the physiological and pathological aspects of both players, information about their mutual relationships is scarce. In the review we attempted to show various examples where both, endocrine disruptors and microbiota are meeting and can act cooperatively or in opposition and to show the mechanism, if known, staying behind these actions.

• MeSH
• endokrinní disruptory farmakologie   MeSH
• fyziologie bakterií účinky léků   MeSH
• gastrointestinální trakt účinky léků   mikrobiologie   MeSH
• látky znečišťující životní prostředí farmakologie   MeSH
• lidé MeSH
• střevní mikroflóra účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• endokrinní disruptory MeSH
• látky znečišťující životní prostředí MeSH

The aim of our study was to reveal the in vitro effects of Salvia officinalis L. (37.5, 75, 150, 200, 250, 300 and 600 µg/ml) extract on the TM3 Leydig cell viability, membrane integrity, steroidogenesis and reactive oxygen species production after 24 h and 48 h cultivation. For the present study, the extract prepared from Salvia officinalis L. leaves was analysed by high performance liquid chromatography (HPLC) for selected flavonoids and phenolic acids followed by a determination of its free radicals scavenging activity (DPPH). Furthermore, Leydig cell viability was assessed by the mitochondrial toxicity assay (MTT), while the membrane integrity was evaluated by 5- carboxyfluorescein diacetate-acetoxymethyl ester (5-CFDA-AM). The level of steroid hormones was performed by enzyme-linked immunosorbent assay (ELISA) from the culture media, while the superoxide radical generation was measured by the nitroblue tetrazolium chloride (NBT) assay. The results show that experimental concentrations did not damage the cell membrane integrity and viability when present at below 300 µg/ml, it was only at 600 µg/ml that a significant (P<0.05) cell viability decline was observed after a 48 h cultivation. A significant (P<0.05) stimulation of testosterone secretion was recorded at 250 µg/ml for 24 h, while the prolonged cultivation time significantly (P<0.05) increased the testosterone and progesterone production at 150, 200, 250 and 300 µg/ml. Furthermore, none of the selected doses exhibited significant ROS-promoting effects however, the highest dose of Salvia initiated the free radical scavenging activity in cultured mice Leydig cells.

• MeSH
• buněčné linie MeSH
• Leydigovy buňky účinky léků   metabolismus   MeSH
• listy rostlin chemie   účinky léků   MeSH
• myši inbrední BALB C MeSH
• myši nahé MeSH
• myši MeSH
• progesteron biosyntéza   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• rostlinné extrakty farmakologie   MeSH
• šalvěj lékařská chemie   MeSH
• techniky in vitro MeSH
• testosteron biosyntéza   MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• progesteron MeSH
• reaktivní formy kyslíku MeSH
• rostlinné extrakty MeSH
• testosteron MeSH