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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 -
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 -
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 -
Oxidative Medicine and Cellular... 2017Testosterone deficiency, as a potential risk factor for aging and aging-related neurodegenerative disorders, might induce mitochondrial dysfunction and facilitate the...
Testosterone deficiency, as a potential risk factor for aging and aging-related neurodegenerative disorders, might induce mitochondrial dysfunction and facilitate the declines of the nigrostriatal dopaminergic system by exacerbating the mitochondrial defects and increasing the oxidative damage. Thus, how testosterone levels influence the mitochondrial function in the substantia nigra was investigated in the study. The present studies showed that testosterone deficiency impaired the mitochondrial function in the substantia nigra and induced the oxidative damage to the substantia nigra as well as the deficits in the nigrostriatal dopaminergic system. Of four mitochondrial respiratory chain complexes, castration of male rats reduced the activity of mitochondrial complex I and downregulated the expression of ND1 and ND4 of 7 mitochondrial DNA- (mtDNA-) encoded subunits of complex I in the substantia nigra. Supplements of testosterone propionate to castrated male rats ameliorated the activity of mitochondrial complex I and upregulated the expression of mitochondrial ND1 and ND4. These results suggest an important role of testosterone in maintaining the mitochondrial function in the substantia nigra and the vulnerability of mitochondrial complex I to testosterone deficiency. Mitochondrial ND1 and ND4, as potential testosterone targets, were implicated in the oxidative damage to the nigrostriatal dopaminergic system.
Topics: Animals; DNA, Mitochondrial; Dopamine; Dopaminergic Neurons; Male; Mitochondria; Mitochondrial Proteins; NADH Dehydrogenase; Orchiectomy; Oxidative Stress; Rats; Rats, Sprague-Dawley; Substantia Nigra; Testosterone; Testosterone Propionate; Up-Regulation
PubMed: 29138672
DOI: 10.1155/2017/1202459 -
Open Life Sciences 2020Testosterone is often used to improve the physiological function. But increased testosterone levels affect blood lipids and cause inflammation and oxidative stress,...
Testosterone is often used to improve the physiological function. But increased testosterone levels affect blood lipids and cause inflammation and oxidative stress, which are risk factors for vascular diseases. This study aimed at investigating the effects of testosterone on cerebral vascular injury using an established intracranial aneurysm (IA) model. Sixteen-week-old female C57Bl/6 mice were subcutaneously infused with testosterone propionate (TP; 5 mg/kg day) or plain soybean oil (controls) for 6 weeks. After 2 weeks of treatment, mice were given angiotensin II-elastase for another 4 weeks. The results showed that TP significantly increased cell apoptosis and reactive oxygen species production in cerebral artery, together with increases in plasma tumor necrosis factor-α (TNF-α) levels and in urinary 8-isoprostane levels. Plasma assays showed that 2 weeks after TP or soybean oil administration, the high-density lipoprotein (HDL) level was higher in the TP group than in controls. studies showed that testosterone increased TNF-α and monocyte chemotactic protein-1 mRNA and protein expression levels in RAW 264.7 macrophages. In summary, by reducing the HDL level, TP aggravates cerebral artery injury by increasing cell apoptosis, inflammation, and oxidative stress.
PubMed: 33817290
DOI: 10.1515/biol-2020-0107 -
Biological & Pharmaceutical Bulletin Jan 2019Veratrum maackii (VM), a perennial plant in the Melanthiaceae family, has anti-hypertensive, anti-cholinergic, anti-asthmatic, anti-tussive, anti-fungal,...
Veratrum maackii (VM), a perennial plant in the Melanthiaceae family, has anti-hypertensive, anti-cholinergic, anti-asthmatic, anti-tussive, anti-fungal, anti-melanogenesis, and anti-tumor activities. Here, we investigated the therapeutic effect of VM on benign prostatic hyperplasia (BPH) in human normal prostate cell line (WPMY-1) and a testosterone propionate-induced BPH animal model. WPMY-1 cells were treated with VM (1-10 µg/mL) and testosterone propionate (100 nM). BPH in rats was generated via daily subcutaneous injections of testosterone propionate (3 mg/kg) dissolved in corn oil, for 4 weeks. VM (150 mg/kg) was administered daily for 4 weeks by oral gavage concurrently with the testosterone propionate. All rats were sacrificed and the prostates were dissected, weighed, and subjected to histological, immunohistochemical, and biochemical examinations. Immunoblotting experiments indicated that WPMY-1 cells treated testosterone propionate had increased expression of prostate specific antigen (PSA) and androgen receptor (AR), and treatment with VM or finasteride blocked this effect. In rat model, VM significantly reduced prostate weight, prostatic hyperplasia, prostatic levels of dihydrotestosterone (DHT), and expression of proliferation markers such as proliferating cell nuclear antigen (PCNA) and cyclin D1, but increased the expression of pro-apoptotic Bcl-2-associated X protein (Bax) and the cleavage of caspase-3. VM administration also suppressed the testosterone propionate-induced activation of nuclear factor-kappaB (NF-κB). Our results indicate that VM effectively represses the development of testosterone propionate-induced BPH, suggesting it may be a useful treatment agent for BPH.
Topics: Animals; Cell Line; Cell Survival; Dose-Response Relationship, Drug; Humans; Male; Plant Extracts; Prostatic Hyperplasia; Rats; Rats, Sprague-Dawley; Testosterone Propionate; Treatment Outcome; Veratrum
PubMed: 30381617
DOI: 10.1248/bpb.b18-00313 -
Saudi Pharmaceutical Journal : SPJ :... Jul 2023Benign prostatic hyperplasia (BPH) is a common urinary disease among the elderly, characterized by abnormal prostatic cell proliferation. Neferine is a dibenzyl...
Benign prostatic hyperplasia (BPH) is a common urinary disease among the elderly, characterized by abnormal prostatic cell proliferation. Neferine is a dibenzyl isoquinoline alkaloid extracted from and has antioxidant, anti-inflammatory and anti-prostate cancer effects. The beneficial therapeutic effects and mechanism of action of neferine in BPH remain unclear. A mouse model of BPH was generated by subcutaneous injection of 7.5 mg/kg testosterone propionate (TP) and 2 or 5 mg/kg neferine was given orally for 14 or 28 days. Pathological and morphological characteristics were evaluated. Prostate weight, prostate index (prostate/body weight ratio), expression of type Ⅱ 5α-reductase, androgen receptor (AR) and prostate specific antigen were all decreased in prostate tissue of BPH mice after administration of neferine. Neferine also downregulated the expression of pro-caspase-3, uncleaved PARP, TGF-β1, TGF-β receptor Ⅱ (TGFBR2), p-Smad2/3, N-cadherin and vimentin. Expression of E-cadherin, cleaved PARP and cleaved caspase-3 was increased by neferine treatment. 1-100 μM neferine with 1 μM testosterone or 10 nM TGF-β1 were added to the culture medium of the normal human prostate stroma cell line, WPMY-1, for 24 h or 48 h. Neferine inhibited cell growth and production of reactive oxygen species (ROS) in testosterone-treated WPMY-1 cells and regulated the expression of androgen signaling pathway proteins and those related to epithelial-mesenchymal transition (EMT). Moreover, TGF-β1, TGFBR2 and p-Smad2/3, N-cadherin and vimentin expression were increased but E-cadherin was decreased after 24 h TGF-β1 treatment in WPMY-1 cells. Neferine reversed the effects of TGF-β1 treatment in WPMY-1 cells. Neferine appeared to suppress prostate growth by regulating the EMT, AR and TGF-β/Smad signaling pathways in the prostate and is suggested as a potential agent for BPH treatment.
PubMed: 37293563
DOI: 10.1016/j.jsps.2023.05.004 -
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 -
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 Ginseng Research May 2022Benign prostatic hyperplasia (BPH) is a disease characterized by abnormal proliferation of the prostate, which occurs frequently in middle-aged men. In this study, we...
BACKGROUND
Benign prostatic hyperplasia (BPH) is a disease characterized by abnormal proliferation of the prostate, which occurs frequently in middle-aged men. In this study, we report the effect of red ginseng oil (KGC11) on BPH.
METHODS
The BPH-induced Sprague-Dawley rats were divided into seven groups: control, BPH, KGC11 25, 50, 100, 200, and finasteride groups. KGC11 and finasteride were administered for 8 weeks. The BPH biomarkers, DHT, 5AR1, and 5AR2, androgen receptor, prostate-specific antigen (PSA), Bax, Bcl-2, and TGF-β were determined in the serum and prostate tissue. The cell viability after KGC11 treatment was determined using BPH-1 cells, and, androgen receptor, Bax, Bcl-2, and TGF-β were confirmed by western blotting.
RESULTS
In the in vivo study, administration of KGC11 reduced prostate weight by 18%, suppressed DHT (up to 22%) and 5AR2 (up to 12%) levels from administration of 100 mg/kg KGC11 (P < 0.05). PSA was significantly downregulated dose-dependently from at the concentration of 50 mg/kg KGC11 (P < 0.05). BPH-1 cell viability significantly reduced through the treatment with KGC11. and , AR, Bcl-2 TGF-β levels reduced significantly but Bax was increased (P < 0.05).
CONCLUSION
These results suggest that KGC11 may inhibit the development of BPH by significantly reducing the levels of BPH biomarkers via 5ARI, anti-androgenic effect, and anti-proliferation effect, serving as a potential functional food for treating BPH.
PubMed: 35600774
DOI: 10.1016/j.jgr.2021.11.005