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Heliyon Jul 2021Leptin and hypothalamic-adipose lipid handling are relevant in determining the shift of metabolic activities. There are scanty findings connecting glucose dysregulation...
Leptin and hypothalamic-adipose lipid handling are relevant in determining the shift of metabolic activities. There are scanty findings connecting glucose dysregulation as a result of hyperandrogenism during gestation to hypothalamic-adipose axis and leptin resistance. Sildenafil has recently gained attention in the prevention of intra-uterine growth restriction. The present study aimed at demonstrating the effect of sildenafil on leptin resistance and hypothalamic-adipose lipid handling in testosterone-exposed pregnant rats. Three groups of pregnant Wistar rats (n = 5/group) received olive oil (Ctr, S.C.) or testosterone propionate (Tes, 3.0 mg/kg; sc)or testosterone propionate (3.0 mg/kg; sc) and sildenafil (Tes + PDE5, 50 mg/kg; )from gestational day 14-19. Blood samples, hypothalamus and adipose tissue were excised for biochemical analysis on day 20. Adipose and body weights, plasma leptin and adiponectin, adipose and hypothalamic leptin and triglyceride, adipose uric acid, hypothalamic Nrf2, catalase and nitric oxide were reduced following gestational testosterone exposure. Also, fasting insulin, plasma triglyceride, uric acid, leptin-adiponectin ratio, hypothalamic free fatty acid, total cholesterol, uric acid, aspartate transaminase and cyclic guanine monophosphate were elevated by testosterone exposure to pregnant animals. Sildenafil ameliorated leptin resistance and normalized hypothalamic-adipose lipid handling. Therefore, sildenafil protects against testosterone-induced leptin resistance and adverse hypothalamic-adipose lipid handling in pregnant rats.
PubMed: 34337184
DOI: 10.1016/j.heliyon.2021.e07574 -
Andrology Jul 2021Recent studies have noted that the circulating testosterone concentration may affect the ability of spermatozoa to survive cryopreservation. However, few attempts to...
BACKGROUND
Recent studies have noted that the circulating testosterone concentration may affect the ability of spermatozoa to survive cryopreservation. However, few attempts to confirm such a relationship have been made. Wild ruminant species have very marked seasonal changes in their reproductive function and strong annual changes in their plasma testosterone concentration.
OBJECTIVES
The present work examines the influence of induced changes in testosterone secretion on sperm variables following conventional slow freezing and ultra-rapid freezing, using the Iberian ibex as an experimental model.
MATERIALS AND METHODS
In a first experiment, testosterone levels were reduced in the middle of the rutting season (December) using the antiandrogen cyproterone acetate (CA). In a second experiment, testosterone levels were increased at the end of the rutting season (January) via the use of the androgen testosterone propionate (TP).
RESULTS
During December, the testosterone concentration was found to be higher in the blood and seminal plasma of untreated males than in those of CA-treated males (p < 0.001 and p < 0.05, respectively). Compared with controls, the TP-treated animals had higher blood plasma testosterone concentrations but lower seminal plasma testosterone concentrations during January (p < 0.01 and p < 0.001, respectively). The seminal vesicles of the TP-treated males were larger than those of untreated males (p < 0.05). When CA was administered, sperm viability improved compared with controls (p < 0.05), irrespective of the freezing protocol followed. For the ultra-rapid freezing procedure, the cryoresistance ratio for motility decreased when TP was administered (p < 0.05). The values for fresh sperm morphometric variables decreased during the 50 days after the end of CA treatment (p < 0.001) and increased over the same time after the end of TP treatment (p < 0.001).
DISCUSSION AND CONCLUSION
The circulating testosterone concentration appears to influence sperm cryoresistance. This may explain the seasonal changes seen in sperm freezability in some species, independent of fresh sperm quality.
Topics: Animals; Cryopreservation; Goats; Male; Models, Theoretical; Semen Preservation; Spermatozoa; Testosterone
PubMed: 33686789
DOI: 10.1111/andr.12998 -
The Journal of Physiological Sciences :... Sep 2019Serum testosterone concentration decreases with age in humans and rodents. Accordingly, old male mice show changes in locomotor activity rhythms: a lengthened...
Serum testosterone concentration decreases with age in humans and rodents. Accordingly, old male mice show changes in locomotor activity rhythms: a lengthened free-running period and decreased activity levels among others. To investigate whether testosterone replacement improves the age-related decline in circadian rhythmicity, we examined the effects of testosterone on the circadian rhythms of wheel running activity in old male mice. Intact male C57BL/6J mice (18-22 months old) were subcutaneously implanted with silicone tubes packed with testosterone propionate (TP) or cholesterol. TP treatment significantly decreased the daily wheel running revolutions in a normal light/dark (LD) cycle and in constant darkness (DD), but did not affect the free-running period. The same experiment performed on young male gonadectomized mice (3-5 months old) demonstrated that TP treatment significantly increased activity levels in both LD and DD. These results suggest that testosterone replacement exacerbates the age-related decline in circadian rhythmicity.
Topics: Animals; Circadian Rhythm; Darkness; Light; Male; Mice; Mice, Inbred C57BL; Motor Activity; Photoperiod; Testosterone
PubMed: 31301005
DOI: 10.1007/s12576-019-00695-4 -
American Journal of Cancer Research 2021Colorectal cancer (CRC) is known to occur more frequently in males than in females, with sex hormones reportedly influencing the development. The purpose of the study...
Colorectal cancer (CRC) is known to occur more frequently in males than in females, with sex hormones reportedly influencing the development. The purpose of the study was to investigate whether orchiectomy in C57BL/6 male mice reduces colorectal tumorigenesis and whether testosterone administration increases tumorigenesis after orchiectomy in an azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model. Clinical symptoms, including colitis and tumor incidence, were evaluated in the absence or presence of testosterone in AOM/DSS-treated male, as well as orchiectomized (ORX) male and female mice. The levels of serum testosterone and colonic myeloperoxidase, interleukin (IL)-1β, and IL-6 were measured by ELISA. Target mRNA expression was assessed by quantitative real-time PCR. Orchiectomy significantly diminished the AOM/DSS-induced colitis indices, including disease activity index, colon shortening, and histological severity at week 2, and decreased tumor numbers and incidence rates in the distal part of the colon increased following AOM/DSS administration at week 13; this reduction was reversed by testosterone supplementation. Furthermore, it was confirmed that the ELISA level (MPO and IL-1β) and the mRNA expression of the inflammatory mediators (COX-2 and iNOS) were maintained at high levels in the tumors of the testosterone-treated group compared with AOM/DSS groups. Interestingly, both endogenous and exogenous testosterone administrations were associated with tumor development (> 2 mm in size) and submucosal invasive cancer. Based on multivariate logistic regression analysis, testosterone was identified as a reasonable hazard factor for the progression of submucosal invasive cancer of the distal colon. In conclusion, endogenous and exogenous testosterone presented a stimulating effect on AOM/DSS-induced colitis and carcinogenicity.
PubMed: 34249451
DOI: No ID Found -
Toxicology Reports 2021Testosterone induces intra-uterine growth restriction (IUGR) with maternal glucose dysregulation and oxidant release in various tissues. Adiponectin, which modulates the...
Testosterone induces intra-uterine growth restriction (IUGR) with maternal glucose dysregulation and oxidant release in various tissues. Adiponectin, which modulates the antioxidant nuclear factor erythroid 2-related factor 2 (Nrf2) signaling is expressed in the placenta and affects fetal growth. Sildenafil, a phosphodiesterase type 5 inhibitor (PDE5i), used mainly in erectile dysfunction has been widely studied as a plausible pharmacologic candidate in IUGR. Therefore, the present study sought to determine the effect of PDE5i on placental adiponectin/Nrf2 pathway in gestational testosterone-induced impaired glucose tolerance and fetal growth. Fifteen pregnant Wistar rats were allotted into three groups (n = 5/group) receiving vehicles (Ctr; distilled water and olive oil), testosterone propionate (Tes; 3.0 mg/kg; sc) or combination of testosterone propionate (3.0 mg/kg; sc) and sildenafil (50.0 mg/kg; ) from gestational day 14-19. On gestational day 20, plasma and placenta homogenates were obtained for biochemical analysis as well as fetal biometry. Pregnant rats exposed to testosterone had 4-fold increase in circulating testosterone compared with control (20.9 ± 2.8 vs 5.1 ± 1.7 ng/mL; p < 0.05) whereas placenta testosterone levels were similar in testosterone- and vehicle-treated rats. Exposure to gestational testosterone caused reduction in fetal and placental weights, placental Nrf2 and adiponectin. Moreover, impaired glucose tolerance, elevated plasma triglyceride-glucose (TyG) index, placental triglyceride, total cholesterol, lactate, malondialdehyde and alanine aminotransferase were observed in testosterone-exposed rats. Treatment with sildenafil improved glucose tolerance, plasma TyG index, fetal and placental weights and reversed placental adiponectin in testosterone-exposed pregnant rats without any effect on placental Nrf2. Therefore, in testosterone-exposed rats, sildenafil improves impaired glucose tolerance, poor fetal outcome which is accompanied by augmented placental adiponectin regardless of depressed Nrf2.
PubMed: 34277360
DOI: 10.1016/j.toxrep.2021.06.011 -
Frontiers in Immunology 2020Both supraphysiological and subphysiological testosterone levels are associated with increased cardiovascular risk. Testosterone consumption at supraphysiological doses...
Both supraphysiological and subphysiological testosterone levels are associated with increased cardiovascular risk. Testosterone consumption at supraphysiological doses has been linked to increased blood pressure, left ventricular hypertrophy, vascular dysfunction, and increased levels of inflammatory markers. Activation of the NLRP3 inflammasome contributes to the production of proinflammatory cytokines, leading to cardiovascular dysfunction. We hypothesized that supraphysiological levels of testosterone, via generation of mitochondrial reactive oxygen species (mROS), activates the NLRP3 inflammasome and promotes vascular dysfunction. Male, 12 week-old C57Bl/6J (WT) and NLRP3 knockout (NLRP3) mice were used. Mice were treated with testosterone propionate [TP (10 mg/kg) ] or vehicle for 30 days. In addition, vessels were incubated with testosterone [Testo (10 M, 2 h) ]. Testosterone levels, blood pressure, vascular function (thoracic aortic rings), pro-caspase-1/caspase-1 and interleukin-1β (IL-1β) expression, and generation of reactive oxygen species were determined. Testosterone increased contractile responses and reduced endothelium-dependent vasodilation, both and . These effects were not observed in arteries from NLRP3 mice. Aortas of TP-treated WT mice (), as well as aortas from WT mice incubated with testo (), exhibited increased mROS levels and increased caspase-1 and IL-1β expression. These effects were not observed in arteries from NLRP3 mice. Flutamide [Flu, 10 M, androgen receptor (AR) antagonist], carbonyl cyanide m-chlorophenyl hydrazone (CCCP, 10 M, mitochondrial uncoupler) and MCC950 (MCC950, 10 M, a NLRP3 receptor inhibitor) prevented testosterone-induced mROS generation. Supraphysiological levels of testosterone induce vascular dysfunction via mROS generation and NLRP3 inflammasome activation. These events may contribute to increased cardiovascular risk.
Topics: Androgens; Animals; Aorta, Thoracic; Caspase 1; Inflammasomes; Interleukin-1beta; Male; Mice, Inbred C57BL; Mice, Knockout; Mitochondria; NLR Family, Pyrin Domain-Containing 3 Protein; Reactive Oxygen Species; Receptors, Androgen; Testosterone Propionate; Tissue Culture Techniques; Vasoconstriction; Vasodilation
PubMed: 32849566
DOI: 10.3389/fimmu.2020.01647 -
Journal of Environmental Science and... 2023Perfluorooctanoic acid (PFOA) is an enduring synthetic chemical that harms human health. Recent studies indicate heightened bioaccumulation of PFOA, particularly in...
Perfluorooctanoic acid (PFOA) is an enduring synthetic chemical that harms human health. Recent studies indicate heightened bioaccumulation of PFOA, particularly in pregnant women experiencing preeclampsia. Since plasma testosterone levels are elevated in pregnant women with preeclampsia, we hypothesized that hyperandrogenic conditions during pregnancy may hinder PFOA elimination and contribute to their higher body burden. Pregnant Sprague-Dawley rats were s/c injected with vehicle or testosterone propionate from gestational day (GD) 15 to 20 to increase plasma testosterone levels by 2-fold, similar to levels in preeclampsia. On GD 16, [C]-PFOA (9.4 pmol/kg) was given intravenously, and subsequently, C radioactivity was measured in maternal blood, urine, feces, and tissues. PFOA was primarily eliminated through urine; however, less PFOA was excreted in urine of pregnant rats with elevated testosterone levels than controls. Fecal excretion of PFOA was minimal and did not significantly differ between groups. The total elimination of PFOA (urine plus feces) was significantly reduced by 12% in pregnant rats with elevated testosterone levels. In controls, PFOA distribution was highest in placenta, followed by the kidneys, liver, brain, heart, lungs, and spleen. Pregnant rats with elevated testosterone levels displayed 12% higher concentrations of PFOA in these tissues than controls. Furthermore, the renal expression of and was significantly decreased, while and expression was significantly increased in pregnant rats with elevated testosterone levels than controls. In conclusion, elevated maternal testosterone levels decrease urinary elimination of PFOA, possibly through altered expression of renal transporters leading to increased tissue concentrations of PFOA in pregnant rats.
PubMed: 37654976
DOI: 10.26502/jesph.96120193 -
Biological & Pharmaceutical Bulletin 2021We previously reported androgen-dependent sex and breed differences in the amounts of mRNAs of CYP isoforms in the pig liver. To clarify whether there are such sex and... (Comparative Study)
Comparative Study
We previously reported androgen-dependent sex and breed differences in the amounts of mRNAs of CYP isoforms in the pig liver. To clarify whether there are such sex and breed differences in the kidney, we examined the amounts of several CYP mRNAs in the kidney using both sexes of 5-month-old Landrace, Meishan and/or their crossbred F (LM and ML) pigs. Significant sex differences in the amounts of several CYP mRNAs were found: male < female for CYP2A19 and CYP3A29; and male > female for CYP4A24/25 in all the breeds. Sex differences in the amount of CYP2B22 mRNA (male < female) and in CYP2C33 and CYP2C49 mRNAs (male > female) were also observed in all the breeds except Landrace pigs. Furthermore, a significant sex difference (male < female) in CYP3A46 mRNA was only found in LM and ML pigs. No significant sex differences were found in either Landrace or Meishan pigs for CYP1A1, CYP1A2 and CYP4B1 mRNAs. The amounts of CYP2C33 and CYP4A24/25 mRNAs in males were higher in Meishan pigs than in Landrace pigs. Additional experiments using pigs treated by castration and/or testosterone propionate indicated that sex and breed differences in the amounts of those CYP mRNAs were, at least in part, dependent on the levels of serum testosterone. Furthermore, the effects of androgen on the amounts of CYP mRNAs in the kidney did not necessarily correlate with those in the liver, suggesting that there is a tissue-selective factor responsible for the androgen-related expression of CYP genes.
Topics: Androgens; Animals; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP1A1; Cytochrome P-450 CYP1A2; Cytochrome P-450 Enzyme System; Female; Gene Expression Regulation, Enzymologic; Kidney; Liver; Male; Orchiectomy; RNA, Messenger; Sex Characteristics; Species Specificity; Sus scrofa; Testosterone Propionate
PubMed: 34334497
DOI: 10.1248/bpb.b21-00333 -
Psychoneuroendocrinology Mar 2020Testosterone has been shown to have dose-dependent effects on spatial memory in males, but the effects of aging upon this relationship remain unclear. Additionally, the...
Testosterone has been shown to have dose-dependent effects on spatial memory in males, but the effects of aging upon this relationship remain unclear. Additionally, the mechanism by which testosterone regulates memory is unknown, but may involve changes in brain-derived neurotrophic factor (BDNF) within specific brain regions. We tested the effects of age and testosterone on spatial memory among male rats using two spatial memory tasks: an object-location memory task (OLMT) and the radial-arm maze (RAM). Castration had minimal effect on performance on the RAM, but young rats (2 months) performed significantly fewer working memory errors than aged rats (20 months), and aged rats performed significantly fewer reference memory errors. Both age and castration impaired performance on the OLMT, with only the young rats with intact gonads successfully performing the task. Subsequent experiments involved daily injections of either drug vehicle or one of four doses of testosterone propionate (0.125, 0.250, 0.500, and 1.00 mg/rat) given to castrated aged males. On the RAM, a low physiological dose (0.125 mg) and high doses (0.500-1.000 mg) of testosterone improved working memory, while an intermediate dose (0.250 mg) did not. On the OLMT, only the 0.250 mg T group showed a significant increase in exploration ratios from the exposure trials to the testing trials, indicating that this group remembered the position of the objects. Brain tissue (prefrontal cortex, hippocampus, and striatum) was collected from all subjects to assay BDNF. We found no evidence that testosterone influenced BDNF, indicating that it is unlikely that testosterone regulates spatial memory through changes in BDNF levels.
Topics: Aging; Animals; Brain; Dose-Response Relationship, Drug; Hippocampus; Male; Memory, Short-Term; Mental Recall; Rats; Space Perception; Spatial Memory; Testosterone
PubMed: 31901624
DOI: 10.1016/j.psyneuen.2019.104550 -
PloS One 2023One of the most prevalent chronic conditions affecting older men is benign prostatic hyperplasia (BPH), causing severe annoyance and embarrassment to patients. The...
Diacerein provokes apoptosis, improves redox balance, and downregulates PCNA and TNF-α in a rat model of testosterone-induced benign prostatic hyperplasia: A new non-invasive approach.
One of the most prevalent chronic conditions affecting older men is benign prostatic hyperplasia (BPH), causing severe annoyance and embarrassment to patients. The pathogenesis of BPH has been connected to epithelial proliferation, inflammation, deranged redox balance, and apoptosis. Diacerein (DIA), the anthraquinone derivative, is a non-steroidal anti-inflammatory drug. This study intended to investigate the ameliorative effect of DIA on the prostatic histology in testosterone-induced BPH in rats. BPH was experimentally induced by daily subcutaneous injection of testosterone propionate for four weeks. The treated group received DIA daily for a further two weeks after induction of BPH. Rats' body and prostate weights, serum-free testosterone, dihydrotestosterone, and PSA were evaluated. Prostatic tissue was processed for measuring redox balance and histopathological examination. The BPH group had increased body and prostate weights, serum testosterone, dihydrotestosterone, PSA, and oxidative stress. Histologically, there were marked acinar epithelial and stromal hyperplasia, inflammatory infiltrates, and increased collagen deposition. An immunohistochemical study showed an increase in the inflammatory TNF-α and the proliferative PCNA markers. Treatment with DIA markedly decreased the prostate weight and plasma hormones, improved tissue redox balance, repaired the histological changes, and increased the proapoptotic caspase 3 expression besides the substantial reduction in TNF-α and PCNA expression. In conclusion, our study underscored DIA's potential to alleviate the prostatic hyperplastic and inflammatory changes in BPH through its antioxidant, anti-inflammatory, antiproliferative, and apoptosis-inducing effects, rendering it an effective, innovative treatment for BPH.
Topics: Animals; Male; Rats; Anti-Inflammatory Agents; Apoptosis; Dihydrotestosterone; Oxidation-Reduction; Plant Extracts; Proliferating Cell Nuclear Antigen; Prostate-Specific Antigen; Prostatic Hyperplasia; Rats, Sprague-Dawley; Testosterone; Tumor Necrosis Factor-alpha
PubMed: 37943844
DOI: 10.1371/journal.pone.0293682