- In utero exposure to bisphenol A disrupts fetal testis development in rats. [Journal Article]
- EPEnviron Pollut 2018 Dec 07; 246:217-224
- Bisphenol A (BPA) is widely used in consumer products and is a potential endocrine disruptor linked with abnormal development of male reproductive tract. However, its action and its effects on the pa...
Bisphenol A (BPA) is widely used in consumer products and is a potential endocrine disruptor linked with abnormal development of male reproductive tract. However, its action and its effects on the pathways in the development of male gonad are still unclear. Here we report that effects of BPA exposure during gestation on male gonad development. Sprague-Dawley rats were gavaged daily with BPA (0, 4, 40, and 400 mg/kg body weight) from gestational day 12 to day 21. BPA dose-dependently decreased serum testosterone levels (0.45 ± 0.08 ng/ml and 0.32 ± 0.08 ng/ml for 40 and 400 mg/kg BPA, respectively) versus the control level (1.11 ± 0.22 ng/ml, Mean ± SE). BPA lowered Leydig cell Insl3 and Hsd17b3 mRNA and their protein levels at doses of 40 and 400 mg/kg. BPA also lowered Leydig cell (Lhcgr, Cyp11a1, and Cyp17a1) and Sertoli cell (Amh) mRNA and their protein levels at 400 mg/kg. BPA decreased fetal Leydig cell number via inhibiting their proliferation, but it did not affect fetal Sertoli cell number. In conclusion, the current study shows that in utero exposure to BPA inhibits fetal Leydig and Sertoli cell differentiation, possibly disrupting the development of male reproductive tract.
- Preventing secondary exposure to women from men applying a novel nestorone/testosterone contraceptive gel. [Journal Article]
- AAndrology 2018 Dec 16
- CONCLUSIONS: Secondary transfer of T and NES occurs after intensive skin contact with the gel application site. Secondary transfer is decreased by a shirt barrier or showering before contact.
- In utero Exposure to Atrazine Disrupts Rat Fetal Testis Development. [Journal Article]
- FPFront Pharmacol 2018; 9:1391
- Atrazine (ATR) is a commonly used agricultural herbicide and a potential endocrine disruptor that may cause testicular dysgenesis. The objective of the present study was to investigate the effects of...
Atrazine (ATR) is a commonly used agricultural herbicide and a potential endocrine disruptor that may cause testicular dysgenesis. The objective of the present study was to investigate the effects of atrazine on fetal testis development after in utero exposure. Female Sprague-Dawley rats were gavaged daily with vehicle (corn oil, control) or atrazine (25, 50, and 100 mg/kg body weight/day) from gestational day 12 to 21. Atrazine dose-dependently decreased serum testosterone levels of male pups, with a significant difference from the control recorded at a dose of 100 mg/kg. In addition, atrazine significantly increased fetal Leydig cell aggregation at a dose of 100 mg/kg. Atrazine increased fetal Leydig cell number but not Sertoli cell number. However, atrazine down-regulated Scarb1 and Cyp17a1 in the fetal Leydig cell per se and Hsd17b3 and Dhh in the Sertoli cell per se. These results demonstrated that in utero exposure to atrazine disrupted rat fetal testis development.
- Dibutyltin Dichloride Retards Leydig Cell Developmental Regeneration in Adult Rat Testis. [Journal Article]
- FPFront Pharmacol 2018; 9:1320
- Dibutyltin dichloride (DBTCl), widely used as plastic stabilizer, can cause comprehensive toxicity. The present study aims to investigate the effects of DBTCl on rat Leydig cell developmental regener...
Dibutyltin dichloride (DBTCl), widely used as plastic stabilizer, can cause comprehensive toxicity. The present study aims to investigate the effects of DBTCl on rat Leydig cell developmental regeneration and characterize the related mechanism. Adult male Sprague Dawley rats were randomly divided into four groups and gavaged with saline (control) or 5, 10, or 20 mg/kg/day of DBTCl consecutively for 10 days. At the end of the DBTCl treatment, all rats received a single intraperitoneal injection (i.p.,) of 75 mg/kg ethane dimethane sulfonate (EDS) to eliminate all the adult Leydig cells and to induce Leydig cell developmental regeneration. Leydig cell developmental regeneration was evaluated by measuring the levels of serum testosterone, luteinizing hormone, and follicle-stimulating hormone on days 7, 35, and 56 post-EDS. Leydig cell gene and protein expression levels, as well as cell morphology and cell counts were also carried out on day 56 post-EDS. The present study found that DBTCl significantly reduced serum testosterone levels on days 35 and 56 post-EDS, but increased serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels on day 56 at ≥ 5 mg/kg/day. The mRNA and protein levels of Leydig (Lhcgr, Scarb1, Star, Cyp11a1, Hsd17b3, and Hsd11b1) and Sertoli cells (Fshr, Amh, and Sox9) were significantly downregulated in the DBTCl-treated testes compared to the control. Immunohistochemical staining showed that DBTCl-treatment caused fewer regenerated Leydig cells and impaired Sertoli cell development and function in the testis on day 56 post-EDS. In conclusion, the present study demonstrates that DBTCl retards rat Leydig cell developmental regeneration by downregulating steroidogenesis-related enzymes at the gene and protein levels, inhibiting Leydig cell proliferation and impairing Sertoli cell function and development.
- Quantitative trait loci that determine plasma insulin levels in F2 intercross populations produced from crosses between DDD/Sgn and C57BL/6J inbred mice. [Journal Article]
- JGJ Genet 2018; 97(5):1413-1420
- When compared to C57BL/6J (B6) mice, DDD/Sgn (DDD) mice has substantially higher plasma insulin levels in both sexes. In this study, we performed quantitative trait loci (QTL) mapping of plasma insul...
When compared to C57BL/6J (B6) mice, DDD/Sgn (DDD) mice has substantially higher plasma insulin levels in both sexes. In this study, we performed quantitative trait loci (QTL) mapping of plasma insulin levels in F2 male mice produced by crosses between DDD and B6 mice. By single-QTL scans, we identified one significant QTL on chromosome 9. When body weight was included as an additive covariate, we identified two significant QTL on chromosomes 9 and 12; the latter coincided with a QTL that was previously identified in F2 female mice produced by the same two strains. The inheritance mode and the direction of the allelic effect of QTL on chromosome 12 were similar in both sexes, but those on chromosome 9 differed between males and females, suggesting that the QTL on chromosome 9 was sex-specific. Based on phenotypic correlations of plasma insulin levels with body weight and plasma levels of total cholesterol, triglyceride and testosterone, we subsequently assessed whether these insulin QTL explain the variation in other metabolic traits by using a point-wise significance threshold of P = 0.05. QTL on chromosome 12 had no significant effect on any trait. In contrast, QTL on chromosome 9 had significant effects on body weight and total cholesterol level. We postulate that Gpr68 and Cyp19a1 are plausible candidate genes for QTL on chromosomes 12 and 9, respectively. These findings provide insight into the genetic mechanisms underlying insulin metabolism.
- Prolactin and Thyroid Stimulating Hormone (TSH) Levels and Sexual Dysfunction in Patients with Schizophrenia Treated with Conventional Antipsychotic Medication: A Cross-Sectional Study. [Journal Article]
- MSMed Sci Monit 2018 Dec 16; 24:9136-9143
- CONCLUSIONS: The incidence of sexual dysfunction was significantly increased in patients with schizophrenia. Hyperprolactinemia and subclinical hypothyroidism were associated with sexual dysfunction, especially in female patients.
- Psychobiological response to an anger induction task in schizophrenia: The key role of anxiety. [Journal Article]
- PRPsychiatry Res 2018 Dec 07; 271:541-547
- In this study an anger induction laboratory task was applied to men with schizophrenia, and resulted in significant changes in different psychophysiological parameters that were measured in a pre-pos...
In this study an anger induction laboratory task was applied to men with schizophrenia, and resulted in significant changes in different psychophysiological parameters that were measured in a pre-post design. We observed a significantly greater self-reported anger mood and negative affection, lower self-reported positive affection, an increase in cardiovascular reactivity (with blood pressure in deeper affection compared to controls), higher salivary testosterone levels, lower salivary cortisol levels, and an increase in right ear items reported in dichotic listening. Furthermore, clinical risk factors related to anger in our patients were analyzed by Stepwise Regression analyses. Trait anger was significantly associated with a higher level of delusional pathology and impulsivity. Regarding the resulted state of anger as an output of the induction, the most relevant finding was that anxiety consistently and significantly predicted the increasing in anger feelings, and, remarkably, it predicted also the increasing in T levels and the cardiovascular reactivity of the patients.
- Longitudinal trajectories of hippocampal and prefrontal contributions to episodic retrieval: Effects of age and puberty. [Journal Article]
- DCDev Cogn Neurosci 2018 Nov 20
- The current study investigated longitudinal change in hippocampal and prefrontal contribution to episodic retrieval. Functional neuroimaging data were collected during an item-context association mem...
The current study investigated longitudinal change in hippocampal and prefrontal contribution to episodic retrieval. Functional neuroimaging data were collected during an item-context association memory task for children between the ages of 8 and 14 with individuals scanned 1-3 times over the course of 0.75-3.7 years (Timepoint 1 N = 90; Timepoint 2 N = 83, Timepoint 3 N = 75). We investigated developmental changes in functional activation associated with episodic retrieval (correct item-context > incorrect item-context contrast) and asked whether pubertal changes contributed to developmental changes in pattern of activation. Non-linear developmental trajectories were observed. In the hippocampus, activation decreased with age during childhood and then increased into early adolescence. In the dorsolateral prefrontal cortex, activation was largely absent initially, but quickly accelerated over time. Independent of age, changes in pubertal status additionally predicted increases in item-context activation in initially older children, and decreases in initially younger children across both regions and two indicators of puberty: the Pubertal Development Scale and salivary testosterone. These findings suggest that changes in both age and pubertal status uniquely contribute to memory-related activation, and the timing of pubertal onset may play an important role in the neural mechanisms supporting memory retrieval.
- Testosterone- and vitamin-grafted cellulose ethers for sustained release of camptothecin. [Journal Article]
- CPCarbohydr Polym 2019 Feb 15; 206:641-652
- Camptothecin (CPT), a potent anticancer drug with known antiviral activity, is halted of clinical use. Few drug delivery systems of CPT are approved for therapy. Hereby, we propose the encapsulation ...
Camptothecin (CPT), a potent anticancer drug with known antiviral activity, is halted of clinical use. Few drug delivery systems of CPT are approved for therapy. Hereby, we propose the encapsulation of hydrophobic CPT in the inner core of cellulose nanoaggregates for sustained release with retaining of antiproliferative activity. Cellulose conjugates were synthesized by esterification of methyl cellulose, hydroxyethyl cellulose and (hydroxypropyl)methyl cellulose with testosterone, ergocalciferol and dl-α-tocopherol hemisuccinates. The degree of substitution attained ranged from 0.004 to 0.025 and no depolymerization was observed by size exclusion chromatography. ATR-FTIR and NMR spectroscopies confirmed grafting of testosterone and vitamins to celluloses. According to dynamic light scattering, it resulted in their self-assembly in aqueous medium as stable and slightly negatively charged nanoaggregates of 213 to 731 nm. Nanoaggregates formation was also assessed using transmission electron and atomic force microscopies. CPT was encapsulated in the cellulose nanoaggregates, achieving a content of 1.7-13.0 wt %. Sustained release of camptothecin over 150 h was observed in simulated physiological conditions. CPT-loaded cellulose nanoparticles appeared to be possible candidates for chemotherapy, according to observed cytotoxicity against MCF-7 cancer cells.
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- The testosterone metabolite 3α-androstanediol inhibits oxidative stress-induced ERK phosphorylation and neurotoxicity in SH-SY5Y cells through an MKP3/DUSP6-dependent mechanism. [Journal Article]
- NLNeurosci Lett 2018 Dec 12
- Testosterone exerts neuroprotective effects on the brain, but the mechanisms by which these effects are exerted appear to be different in males and females. While in females they involve local conver...
Testosterone exerts neuroprotective effects on the brain, but the mechanisms by which these effects are exerted appear to be different in males and females. While in females they involve local conversion to estradiol, in males they may be androgen receptor-dependent, or mediated through metabolism to neurosteroids such as 5α-androstane-3α,17β-diol (3α-diol), which acts through different mechanisms than testosterone itself. Recently, we demonstrated that 3α-diol can protect neurons and neuronal-like cells against oxidative stress-induced neurotoxicity associated with prolonged phosphorylation of the extracellular signal-regulated kinase (ERK). The mechanism(s) responsible for these effects remain unknown. In the present study, we sought to determine whether the ERK-specific phosphatase, mitogen-activated protein kinase phosphatase 3/dual specificity phosphatase 6 (MKP3/DUSP6), is involved in the cytoprotective effects of 3α-diol in SH-SY5Y human female neuroblastoma cells. 3α-diol inhibited ERK phosphorylation and ameliorated cell death induced by the oxidative stressor hydrogen peroxide (H2O2). These protective effects were significantly reduced by pre-treatment with the MKP3/DUSP6 inhibitor BCI. In addition, H2O2 decreased expression of MKP3/DUSP6, and this was prevented by co-treatment with 3α-diol. These findings suggest that the protective effects of 3α-diol are mediated through regulation of ERK phosphorylation in neurotoxic conditions and indicate that these effects may be exerted through modulation of MKP3/DUSP6. Targeting the regulation of MKP3/DUSP6 may be beneficial in reducing toxicity under conditions of oxidative stress.