Decreased Serum Testosterone Research Articles

Berberine alters the gut microbiota metabolism and impairs spermatogenesis.

Berberine (BBR) is used to treat diarrhea clinically. However, its reproductive toxicity is unclear. This study aims to investigate the impact of BBR on the male reproductive system. Intragastric BBR administration for 14 consecutive days results in a significant decrease in the serum testosterone concentration, epididymal sperm concentration, mating rate and fecundity of male mice. Testicular treatment with testosterone propionate (TP) partially reverses the damage caused by BBR to the male reproductive system. Mechanistically, the decrease in Muribaculaceae abundance in the gut microbiota of mice is the principal cause of the BBR-induced decrease in the sperm concentration. Both fecal microbiota transplantation (FMT) and polyethylene glycol (PEG) treatment demonstrate that Muribaculaceae is necessary for spermatogenesis. The intragastric administration of Muribaculaceae intestinale to BBR-treated mice restores the sperm concentration and testosterone levels. Metabolomic analysis reveals that BBR affects arginine and proline metabolism, of which ornithine level is downregulated. Combined analysis via 16S rRNA metagenomics sequencing and metabolomics shows that Muribaculaceae regulates ornithine level. The transcriptomic results of the testes indicate that the expressions of genes related to the low-density lipoprotein receptor (LDLR)-mediated testosterone synthesis pathway decrease after BBR administration. The transcriptional activity of the Ldlr gene in TM3 cells is increased with increased ornithine supplementation in the culture media, leading to increased testosterone synthesis. Overall, this study reveals an association between a BBR-induced decrease in Muribaculaceae abundance and defective spermatogenesis, providing a prospective therapeutic approach for addressing infertility-related decreases in serum testosterone triggered by changes in the gut microbiota composition.

Androgen Exhibits a Protective Role Against Focal Erosions in Murine TNF-induced Inflammatory Arthritis.

Rheumatoid arthritis (RA) is characterized by erosive pathology associated with joint inflammation and a sexual dimorphism with increased prevalence in females. Here, we aim to determine whether androgen is protective against inflammatory-erosive disease in TNF-transgenic (TNF-Tg) mice. Wild-type (WT) and TNF-Tg male mice underwent sham (WT, n = 3; TNF-Tg, n = 7) or orchiectomy (WT, n = 3; TNF-Tg, n = 7) surgery at 1 month old to remove androgen production confirmed by serum testosterone concentration. Cohorts of orchiectomized TNF-Tg males were treated with either 5ɑ-dihydrotestosterone (.025 mg/day) (n = 3) or placebo (n = 3) via subcutaneous pellet insertion. Weekly clinical measures, along with mid-hindpaw bone volumes and ankle histology at 3 months old were evaluated for all groups. Orchiectomies in TNF-Tg males significantly decreased serum testosterone (P < .05), weight gain (P < .001), and mid-hindpaw bone volumes (P < .05) in comparison to sham TNF-Tg mice. The cuboid bone also had increased synovitis by histology with the loss of androgen (P < .05). Treatment of orchiectomized TNF-Tg males with 5ɑ-dihydrotestosterone protected against the changes in weight gain (P < .01) and bone erosion (P < .05) associated with decreased osteoclast number in the cuboid (P < .01). In the TNF-Tg model of chronic inflammatory arthritis, androgen is protective in erosive disease. The loss of endogenous androgen significantly accelerated the progression of inflammatory-erosive arthritis in male TNF-Tg mice to a similar severity as age-matched female mice. In addition, treatment with exogenous androgen prevented this observed bone loss in orchiectomized TNF-Tg males. Overall, androgen delays and limits bone erosion even in the presence of active inflammation and future studies are warranted to elucidate the associated mechanisms.

Exploring the potential of selenium nanoparticles and fabricated selenium nanoparticles @vitamin C nanocomposite in mitigating nicotine-induced testicular toxicity in rats.

The tobacco epidemic signifies a major public health threat. Nicotine (NIC), a major active constituent in tobacco, impedes male fertility and semen quality. This work is implemented to explore the potential of selenium nanoparticles (SeNPs) and the newly fabricated SeNPs @vitamin C (SeNPs@VITC) nanocomposite in mitigating testicular toxicity induced by NIC. The six groups of 48 adult Wistar rats were designed as follows: the control group injected intraperitoneally with normal saline, the SeNPs group treated orally with 2mg/kg of SeNPs, the SeNPs@VITC nanocomposite group treated orally with 2mg/kg of SeNPs@VITC nanocomposite, the NIC group injected intraperitoneally with 1.25mL/kg of NIC, the NIC+ SeNPs group received SeNPs plus NIC, and the NIC+ SeNPs@VITC nanocomposite group received SeNPs@VITC nanocomposite plus NIC. Treatments were administered over a 28-day period. NIC treatment significantly caused poor sperm quality, decreased serum testosterone, increased follicle-stimulating hormone (FSH), luteinizing hormone (LH) concentrations, reduced hemoglobin levels, leukocytosis, disrupted testicular oxidant/antioxidant balance, and disorganized testicular structure. The construction of the novel SeNPs@VITC nanocomposite, compared to NIC plus SeNPs alone, demonstrated a more potent ameliorative effect on NIC-induced reproductive toxicity in adult rats. The SeNPs@VITC nanocomposite significantly increased sperm count, reduced the percentage of sperm head abnormalities, lowered both serum FSH and LH concentrations, and improved the hemoglobin response. Both SeNPs and SeNPs@VITC nanocomposite alleviated the testicular toxicity induced by NIC, but the SeNPs@VITC nanocomposite exhibited superior efficacy. The SeNPs@VITC nanocomposite could be employed to advance enhanced therapeutic strategies for addressing male infertility.

Occupational Hazard Exposure: Assessment of Hypogonadism and Dyslipidemia in House and Automobile Painters in Ilorin, Nigeria

Aims: To investigate the impact of human exposure to the constituents of paint on serum reproductive hormone and Lipid profile among occupationally exposed House and Automobile spray painters in Yakuba district of Ilorin East Local Government area of Kwara State. Nigeria. Study Design: Experimental./ Cross sectional. Place and Duration of Study: Yakuba district of Ilorin East Local Government area of Kwara State. Nigeria, 6months; between July 23 and January 2024. Methodology: 120 male participants were recruited for this study with the mean age 33.15±0.86 years. The participants included 40 automobile painters, 40 house painters, and male artisans who were not painters and served as the control group .Venous Blood samples were collected from both the test and control subjects for the measurement of serum lipids and testosterone using reference techniques. Results: Total Cholesterol, Triglyceride, HD and LDL cholesterol were significantly higher (P&lt;0.05) in the exposed automobile and house painters than the control groups. There was no significant difference (P&gt;0.05) between the serum lipid values of the automobile and the house painters. The serum testosterone level in both group of exposed painters was statistically similar(P&gt;0.05). There was no significant correlation (P&gt;0.05) between the frequency of cars or houses painted per month and work experience with the lipid profile parameters and testosterone levels in the occupationally exposed house and automobile painters. Conclusion: Occupational exposure to some chemical constituents of paint is associated with dyslipidemia and decrease serum testosterone which may precipitate adverse ill health among the painters.

Metabolic Consequences of Polycystic Ovary Syndrome on Hepatic Function in High Fat Diet-Fed Rats: Potential Role of Exercise

Abstract Context Polycystic ovarian syndrome (PCOS) is the most common endocrine-metabolic disorder in reproductive-aged women. Since, The current study was designed to elucidate the metabolic comorbidities of polycystic ovarian syndrome, especially the hepatic effect, with or without high fat diet feeding, and to emphases the crucial role of exercise in managing such complications. Materials and Methods This study was carried out on 55 adult female albino Wistar rats, the study duration was 8 weeks. Rats included in the present study were randomly allocated into five equal groups, eleven rats each: Group I: Control group, Group II: Polycystic ovary syndrome (PCO) group, Group III: High fat diet fed polycystic ovary syndrome (HF-PCO) group, Group IV: Exercise-treated polycystic ovary syndrome (PCO-EX) group, Group V: High fat diet fed exercise-treated polycystic ovary syndrome (HF-PCO-EX) group. PCOS was induced in female wistar rats by oral administration of Letrozole (1mg/kg daily by oral gavage for 21 days in groups II, III, IV, V, high fat diet was supplemented to groups III and V. Rats of groups IV and V were subjected to 30 minutes swimming protocol 5 days/ week for 5 weeks after the period of induction. Results All measured values of the OGTT as well as area under the curve, serum fasting glucose (FG), insulin levels and HOMA-IR were all significantly increased in the PCO, HF-PCO when compared to control group. Compared to their corresponding non exercised groups, both PCO-EX and HFPCO-EX groups showed significant reductions in all parameters except for T90 in PCO-EX group. For the lipid profile, the serum level of TG, TC, LDL-C and AI were all significantly increased while HDL-C was significantly decreased in PCO and HF-PCO compared to control group as well as in HF-PCO group compared to PCO group. PCO-EX and HF-PCO-EX groups showed significant reductions in TG, TC, LDL-C and AI and a significant elevation in HDL-C when compared to their corresponding non- exercised groups. For liver enzymes serum level of ALT, AST and GGT were significantly increased in PCO and HF-PCO groups when compared with control group. Compared to their corresponding non exercised groups, both PCO-EX and HF-PCO-EX showed significant reductions in liver enzymes. As regard the hormonal profile, the serum level of estradiol, adiponectin and adiponectin/resistin ratio (A/R) were significantly decreased while serum level of testosterone, LH and resistin were significantly increased in PCO and HF-PCO groups compared to control group. PCO-EX and HF-PCO-EX groups induced significant increases in serum estradiol, adiponectin and A/R as well as significant decreases in serum testosterone, LH and resistin compared to their corresponding non exercised groups. Conclusion We could conclude that both moderate intensity exercise and avoiding high fat diet have beneficial therapeutic potentials in ameliorating the metabolic effects of PCO syndrome in rats especially the hepatic effects and the development of NAFLD.

Protective roles of some natural and synthetic aromatase inhibitors in testicular insufficiency caused by Bisphenol A exposure

ABSTRACT In our study, the protective role of synthetic aromatase inhibitors anastrozole (ANS), letrozole (LTZ) and exemestane (EXM) and natural aromatase inhibitors resveratrol (RSV) and apigenin (APG) against testicular failure caused by exposure to Bisphenol A (BPA) was investigated. The epididymal sperm concentration, sperm motility and sperm morphology were determined. Oxidative stress and inflammatory response parameters were examined and histological examinations were performed in testicular tissues. Our results revealed that BPA exposure decreased serum testosterone and estrogen levels, increased FSH and LH levels (p < 0.05). BPA has been found to increase oxidative stress and inflammatory response and disrupt the histological structure. Also, BPA exposure decreased testicular weight, epididymal sperm concentration and motility, and increased abnormal sperm rate (p < 0.05). These results show that ANS, LTZ and RSV treatments reduce the BPA-induced testicular damage.

Serum testosterone levels and oxidative stress in type 1 diabetes, type 2 diabetes, and obesity.

Obesity, type 1 diabetes mellitus (T1DM), and type 2 diabetes mellitus (T2DM) are metabolic diseases that continue to be a global problem. Testosterone levels in men are affected by several factors, including obesity and DM. Although the relationship between diabetes and testosterone is not fully understood, oxidative stress is thought to play a major role. The aim of this study was to compare serum testosterone levels and oxidative stress markers [total antioxidant status (TAS), total oxidant capacity (TOS), oxidative stress index (OSI), and ischaemic modified albumin (IMA)] among the control group and experimentally induced obese, T1DM, and T2DM rats. The study included 28 male Sprague-Dawley rats divided into 4 groups: the obesity group were fed a high-fat diet (HFD), the T2DM group received a HFD plus a single dose of streptozocin (STZ), the T1DM group received only STZ, and there was a control group. Serum testosterone, TAS, TOS, OSI, and IMA were analysed. Serum testosterone levels were lower in the T1DM and T2DM groups compared to the control and obesity groups. The TOS levels were highest in the T2DM group, followed by the T1DM group, the obesity group, and finally the control group. No significant difference was found between the obesity group and the control group in terms of TOS levels. Regarding TAS levels, the order observed was control group > obesity group > T2DM > T1DM. Testosterone was positively correlated with TAS and negatively correlated with TOS and OSI. Increased oxidative stress in diabetes may be an important factor that decreases serum testosterone levels.

A novel approach of using Maca root as a radioprotector in a rat testicular damage model focusing on GRP78/CHOP/Caspase-3 pathway

PurposeDespite the effectiveness of ionizing radiation in treating cancer, it can damage healthy tissues in the vicinity. Due to the high radio-sensitivity of testicular tissues, radiation therapy may affect spermatogenesis, which may result in infertility. Hence, in this study testicular damage model is constructed to investigate the mitigation effect of Maca root powder and its potential radioprotective activity through both oxidative and endoplasmic reticulum (ER) stresses, besides the apoptotic pathway. MethodsMale albino rats were exposed to 6Gy of whole-body gamma radiation single dose. Maca root powder (1 g/kg b.wt./day, by oral gavage) was administered for a week before irradiation, then d-galactose (300 mg/kg, by oral gavage) and Maca daily for another week. ResultsGamma radiation and d-galactose revealed a significant decrease in serum testosterone, sperm count, and motility and higher percentage of the sperm head abnormality, while Maca root treatment maintained all sperm morphology parameters. Maca root treatment demonstrated a notable defense against radiation-induced oxidative stress and ameliorated malonaldehyde (MDA), reactive oxygen species (ROS), nitric oxide (NO), glutathione-S-transferase (GST) levels, reduced glutathione (GSH), oxidized glutathione (GSSG) and the ratio of GSH/GSSG in testis tissues. Exposure to gamma rays and d-galactose displayed a significant elevation in GRP78, CHOP, total caspase-3 as well as active (cleaved) caspase-3 levels, whereas treatment with Maca significantly reduced the ER and apoptotic markers levels. Also, Maca improved the histological changes of the disorganized seminiferous tubules induced by irradiation. ConclusionOur findings show for the first time that Maca has a protective effect on male reproductive damage induced by radiotherapy. Maca root reveals anti-apoptotic effect and protection against testicular damage via GRP78/CHOP/caspase-3 pathway.

Effect of platelet rich plasma versus melatonin on testicular injury induced by Busulfan in adult albino rats: a histological and immunohistochemical study

ABSTRACT This study was done to estimate the testicular histological alterations induced by Busulfan (BUS) and compare the possible protective effects of melatonin (MT) and platelet rich plasma (PRP) in a rat model. Sixty-four male rats were dispersed into: control group, BUS group, melatonin group, and PRP group. Blood samples were processed for biochemical analysis. Tissue specimens were managed for light and electron microscopic studies. Immunohistochemical expression of vimentin and proliferating cell nuclear antigen (PCNA) was performed. Busulfan induced severe testicular damage in all studied methodologies. It showed a statistically significant decrease in serum testosterone and elevation of MDA when compared to the control group. Abnormal testicular cytostructures suggesting defective spermatogenesis were observed: distorted seminiferous tubules, deformed spermatogenic cells, low germinal epithelium height, few mature spermatozoa, and also deformed barrier. Vimentin and PCNA expressions were reduced. Ultrastructurally, Sertoli cells and the blood testis barrier were deformed, spermatogenic cells were affected, and mature spermatozoa were few and showed abnormal structure. Both melatonin and PRP induced improvement in all the previous parameters and restoration of spermatogenesis as confirmed by improvement of Johnsen’s score from 2.6 ± .74 to 7.6 ± .92. In conclusion, melatonin and PRP have equal potential to ameliorate the testicular toxicity of BUS. Melatonin can provide a better noninvasive way to combat BUS induced testicular injury.

Long noncoding RNA XIST inhibition promotes Leydig cell apoptosis by acting as a competing endogenous RNA for microRNA-145a-5p that targets SIRT1 in late-onset hypogonadism.

Leydig cell (LCs) apoptosis is responsible for decreased serum testosterone levels during late-onset hypogonadism (LOH). Our study was designed to illustrate the regulatory effect of lncRNA XIST on LCs and to clarify its molecular mechanism of action in LOH. The Leydig cells (TM3) was treated by 300μM H2O2 for 8h to establish Leydig cell oxidative stress model in vitro. The expression levels of lncRNA XIST in the testicular tissues of patients with LOH were measured using fluorescence in situ hybridization (FISH). The interaction between lncRNA XIST/SIRT1 and miR-145a-5p was assessed using starBase and dual-luciferase reporter gene assays. Apoptotic cells and Caspase3 activity were determined by flow cytometry (FCM) assay. Testosterone concentration was determined by ELISA. Moreover, histological assessment of testicles in mice was performed by using HE staining and the TUNEL assay was used to determine apoptosis. We found that the lncRNA XIST was downregulated in the testicular tissues of LOH patients and mice and in H2O2-induced TM3 cells. XIST siRNA significantly promoted apoptosis, enhanced Caspase3 activity and reduced testosterone levels in H2O2-stimulated TM3 cells. Further studies showed that the miR-145a-5p inhibitor reversed the effect of XIST-siRNA on H2O2-induced Leydig cell apoptosis. MiR-145a-5p negatively regulated SIRT1 expression, and SIRT1-siRNA reversed the effects of the miR-145a-5p inhibitor on H2O2 stimulated TM3 cells. The in vivo experiments indicated that silencing of the lncRNA XIST aggravated LOH symptoms in mice. Inhibition of lncRNA XIST induces Leydig cell apoptosis through the miR-145a-5p/SIRT1 axis in the progression of LOH.

Fluorene-9-bisphenol exposure damages the testis in mice through a novel mechanism of ferroptosis

Fluorene-9-bisphenol (BHPF) is an emerging global endocrine-disrupting chemical found in numerous household products as a substitute of bisphenol A. Many studies have reported various toxicities associated with BHPF. However, the effect of BHPF on male reproduction, particularly on the structural integrity of the blood testis barrier (BTB) in mice, has not yet been extensively studied. Ferroptosis, a newly identified form of cell death, occurs in the testicular tissue following exposure to BPA, affecting male fertility. We investigated whether ferroptosis plays a role in BHPF-induced testicular damage. The findings indicated that BHPF exposure led decreases in serum testosterone (T) concentration and sperm concentration and motility in mice. Furthermore, BHPF disrupted the BTB by interfering with key BTB-related proteins, including Cx43, β-catenin, and ZO-1. Moreover, BHPF induced ferroptosis through the induction of lipid peroxidation, iron overload, oxidative stress, and mitochondrial dysfunction in the testicular tissue. Inhibition of ferroptosis using Fer-1 mitigated the BHPF-induced damage to the BTB and ferroptosis in TM4 cells. Overall, our findings indicated the detrimental effects of BHPF on male reproductive function in mice, suggesting ferroptosis as a mechanism underlying testicular damage.

Effects of the adsorption behavior of polyamide microplastics on male reproductive health by reduction of testosterone bioavailability

Microplastics (MPs) are global environmental pollutants with potential toxicity concerns, and their effects on the reproductive system have attracted increasing attention. This study investigated the interaction between MPs and mammalian biomolecules, focusing on the relationship between the testosterone adsorption behavior of MPs and male reproductive health. The adsorption capacity of different types of MPs for testosterone was evaluated in vitro experiments. Polyamide (PA)-MPs exhibited stronger adsorption, while polymethyl methacrylate (PMMA)-MPs displayed the weakest adsorption. Sorption equilibrium between PA-MPs and testosterone was achieved within 6 h, fitting the Pseudo-2nd-order model and Langmuir isotherm. The effects of MPs on male reproduction in mice was determined in vivo experiments. Male mice were treated with 0.1 and 0.5 mg/d PA-MPs/PMMA-MPs by gavage once per day for 28 days. The results showed that only 0.5 mg/d PA-MP exposure induced decreased serum testosterone levels, increased testicular testosterone levels compared to the control, and more severe damage to seminiferous tubule structure, sperm motility and sperm morphology compared to the PMMA-MPs group. Meanwhile, PA-MPs could reduce intracellular nuclear translocation of androgen receptor (AR) mediated by testosterone, while PMMA-MPs had no impact. The study revealed that PA-MP adsorption reduced testosterone bioavailability and caused sperm quality to decline, offering new insights into the combined toxicity mechanism of MPs in male mammals.

Curcumin-loaded chitosan-protamine nanoparticles: A promising approach to ameliorate nicotine-induced reproductive disorders in male rats

Nicotine (NIC) exposure has been shown to impair male fertility, affecting sperm quality and motility. Curcumin (CUR) has been shown to have anti-inflammatory and antioxidant properties and has demonstrated potential in treating a range of health conditions, including infertility. The current study aimed to investigate the effects of curcumin encapsulated in chitosan-protamine nanoparticles (CUR-CPNPs) against nicotine-induced reproductive dysfunction in male rats. CUR-CPNPs were chemically prepared and characterized by TEM imaging, Zetasizer, and FT-IR spectroscopy. eight groups (6 rats per each) of male rats were used: first & second groups acted as control, third group received CUR-CPNPs (250 mg/kg), fourth group received CUR (250 mg/kg), fifth group received CPNPs (250 mg/kg), sixth group received 0.6 mg/kg nicotine (NIC). Finally, seventh and eighth groups are received NIC + CUR, NIC + CUR-CPNPs, respectively. After the end of the treatment period, the rats were anesthetized then the relative weight of the reproductive organs, semen analysis, testosterone levels and oxidative stress biomarkers were assessed, and finally a histopathological analysis of the testicular tissue was performed.The impacts of NIC administration resulted in a significant reduction in relative reproductive organs weights, exacerbated oxidative stress, decreased serum testosterone level, and negatively impacted semen count, motility, and viability. Testicular histopathology revealed extensive degenerative alterations. On the other hand, the ameliorative role of CUR-CPNPs clearly reversed the devastating effect caused by nicotine.

Transcriptomic characterization of interactions between sodium selenite and coenzyme Q10 on preventing cadmium-induced testicular defects

The effect of heavy metal cadmium (Cd) on testicular function is recognized. However, the mechanism involved is not well-established. In the present study, we analyzed the testicular transcriptomic changes induced by acute Cd exposure of adult rats with and without supplementation of antioxidants selenium (Se) and/or coenzyme Q10 (CoQ). Cd significantly decreased serum testosterone and two steroidogenic proteins SCARB1 and STAR. RNA-Seq analyses of testicular RNAs revealed specific activation of oxidative stress-, inflammation-, MAPK- and NF-κB-related signaling molecules. In addition, Cd treatment down-regulated gene for I, III and IV complexes of mitochondrial electron transport chain and up-regulated genes for NADPH-oxidase, major cascade in ROS production. The decrease in steroidogenesis and increase in inflammation may result from oxidative stress since supplementation of Se and CoQ, but not with either alone, almost completely prevented these changes, including overall alterations in transcriptome. Cd exposure induced total of 1192 differentially expressed genes (DEGs), which was reduced to 29 without considering confounding factors associated with Se/CoQ, a 97.6% protection rate. In conclusion, Cd exposure inhibited Leydig cell steroidogenesis by down-regulating SCARB1 and STAR through increasing oxidative stress and inflammation, but Se plus CoQ synergistically prevented all the changes induced by the Cd exposure.

Kigelia africana improves libido in phenyl hydrazine induced anaemic female Wistar rats

Background and Objective: Anaemia is a global public health challenge affecting adolescent girls, women of reproductive age, pregnant women and children in low and middle income countries. This study therefore was designed to evaluate the effect of extract of Kigelia africana on female sexual hormones following phenyl hydrazine induced anaemia. Materials and Methods: This research work was carried out using twenty five (25) female Wistar rats. The experimental rats were randomly divided into five (5) groups, with five animals per group .Group A served as Normal control (non-anaemic control), group B: Anaemic control(induced with phenyhdrazine) without treatment ,group C; anaemic rats treated with feroton (Standard control), group D; Anaemic rats co-administered with 200mg/kg petroleum ether leaf extract Kigelia africana extract (PETLETKG1), and group E; Anaemic rats treated with 200mg/kg between petroleum ether leaf extract Kigelia africana extract (PETLETKG2) .All administrations were done orally using oropharyngeal cannula once per day for 14 days (2 week). Blood was collected by cardiac puncture using disposable syringe and needle to draw blood into plane sterile tubes. Thereafter, the samples were analyzed using standard methods. Results: The result depicts the significant (p&lt;0.05) increase in serum follicle stimulating hormone, prolactin, progesterone, oestrogen when compared with both normal and standard control. More so, the petroleum ether extract of K. africana showed no significant (P&lt;0.05) difference on L.H hormone when compared with both the standard and the normal control. Contrastingly, the extract of K. africana decreases serum testosterone significantly (P&lt;0.05) when compared with both the standard and normal control. Conclusion: The result suggests that the extract might be useful in improving the sexual health and libido of female animals following phenyl hydrazine induced anaemia.

Dietary exposure to an environmentally relevant phthalate mixture alters follicle dynamics, hormone levels, ovarian gene expression, and pituitary gene expression in female mice

Phthalates are chemicals ubiquitously used in industry. Individual phthalates have been found to adversely affect female reproduction; however, humans are exposed to a mixture of phthalates daily, primarily through ingestion. Previous studies show that exposure to an environmentally relevant mixture of phthalates (Mix) can affect female reproduction. Little research, however, has been conducted on the effects of short-term (1 month) and long-term (6 months) exposure to Mix on ovarian functions. Thus, this study tested the hypothesis that short-term and long-term exposure to Mix alters ovarian folliculogenesis, serum hormone concentrations, pituitary gene expression, and ovarian expression of genes involved in steroidogenesis, apoptosis, cell cycle regulation, and oxidative stress. Adult CD-1 female mice were exposed to vehicle control (corn oil) or Mix (0.15–1500 ppm) in the chow for 1 or 6 months. Exposure to Mix for 1 month increased the number of atretic follicles (0.15 ppm), altered ovarian gene expression (0.15 ppm, 1500 ppm), and decreased serum testosterone (1.5 ppm) compared to control. Exposure to Mix for 6 months increased serum follicle-stimulating hormone (FSH) (0.15 ppm), decreased serum luteinizing hormone (LH) (0.15 ppm, 1.5 ppm, and 1500 ppm), decreased serum estradiol (1500 ppm), altered pituitary gene expression (1500 ppm), increased the number (1500 ppm) and percentage (1.5 ppm and 1500 ppm) of primordial follicles, and decreased the percentage of preantral (1500 ppm) and antral (1.5 ppm and 1500 ppm) follicles compared to control. These data indicate that exposure to Mix can alter folliculogenesis, steroidogenesis, and gene expression in female mice.

Dose-Dependent Testicular Injury and Recovery after Total-Body Irradiation in Rhesus Monkeys.

Testicular injury is a well-documented acute effect of radiation exposure, though little is known about recovery years after irradiation, especially at higher doses. We examined the testes from 143 irradiated and control male rhesus monkeys, who were part of the Radiation Late Effects Cohort over a four-year period. Irradiated animals were exposed to doses ranging from 3.5 to 8.5 Gy of total-body irradiation. The testes were assessed using computed tomography (CT) volumetry, serum testosterone, and histology for deceased members of the cohort. Irradiated animals exhibited dose-dependent testicular atrophy as well as decreased serum testosterone during the winter breeding season when compared to age-matched unirradiated controls. No significant difference in summer testosterone levels was observed. Volumetric and histologic evidence of testicular recovery was present approximately three years postirradiation for animals who received ≤8 Gy. The study demonstrates dose-dependent testicular injury after total-body irradiation and provides evidence for volumetric and spermatogonial recovery even at lethal doses of total-body irradiation in rhesus monkeys.

The anti-spermatogenic activity of nanoliposomes loaded with Heracleum persicum phenolic compounds in Balb/C mice.

There are various types of bioactivities that have been reported for Heracleum persicum species, such as antioxidant, anti-inflammatory, and cytotoxicity properties. In the current study, the bio-accessibility of H. persicum bioactive compounds was improved by purifying its phenolic-enriched fractions (PEF) and encapsulating them into nanoliposomes to analyze its cytotoxic impacts on mice testicular tissue and their fertility status. Nano liposomal H. persicum PEF (NL-HPEF) was prepared by ultrasound-based encapsulation of HPEF and L-agranular lecithin mixture. The size, morphology, and stability of NL-HPEF were characterized by dynamic light scattering, field emission scanning electron microscopy, and zeta potential analysis. The 18 white male Balb/c mice (20-25g) at 3 treatment groups were provided to study the NL-HPPF cytotoxicity by measuring the mice liver enzyme including aspartate aminotransferase (AST), ALP and alanine aminotransferase (ALT), testis lipid peroxidation, and testicular tissue destruction levels. Moreover, the mice's fertility was evaluated by studying the Adam3, Prm1, Spata19, and Tnp2 gene expression in the testicular tissues. The obtained results manifested that the synthesized NL-HPEF was stable (193.7nm) and exhibited a notable cytotoxic impact on the mice's liver (ALT and AST enhancement levels) and testicular tissues. Moreover, their increasing treatment doses impaired the male mice's fertility by decreasing the sperm count, viability, and motility. In addition, fertility suppression was verified by decreasing serum testosterone and downregulating the Adam3, Prm1, Spata19, and Tnp2 gene expression in their testicular tissues. The male mice's fertility was significantly (p<0.05) suppressed by increasing treatment doses of NL-HPEF. Hence, the NL-HPEF could be considered a promising alternative to replace the male chemical contraceptives drugs.

Deep-frying palm olein oil-fried street falafel induces testicular toxicity in rats

Falafel is the most common Egyptian street food, and deep-frying palm oil is a commonly used for frying it. The main objective of this research was to evaluate the effect of deep-frying palm olein oil-fried street falafel on testes of Wistar rats. Twenty-one adult male Wistar rats were randomly divided into three equal groups and given treatment as follows: control group received only distilled water, fresh palm olein oil (FPO) group received FPO (1 ml/100 g BW/day) and deep-frying palm olein oil (DPO) group received DPO (1 ml/100 g BW/day) orally for 28 days. Serum level of testosterone, testicular tissue oxidative status, and sperm characteristics were determined. Testicular specimens were processed for histopathological examination. The results revealed that DPO group showed a significant (p<0.01) decrease in serum testosterone with significant (p<0.01) reduction of testicular glutathione, superoxide dismutase, and glutathione peroxidase, whereas testicular malondialdehyde was markedly (p<0.001) raised. There were significant decrease in epididymal sperm count (p<0.01), sperm progress motility (p<0.001), and increase abnormal sperm rate (p<0.001) in DPO group. Testicular histology in DPO group showed structural abnormalities which are compatible with lipid peroxidation and antioxidant deficiency. In Conclusion, deep-frying palm olein oil that used for the frying falafel induces testicular abnormalities in rats.

Knockdown of ZnT4 Induced Apoptosis, Inhibited Proliferation and testosterone synthesis of TM3 cells.

Zinc deficiency has a huge impact on male reproduction. The zinc transporter (ZnT) family is involved in the maintenance of zinc homeostasis and testosterone synthesis. However, the underlying mechanisms remain to be investigated. Therefore, in this study, we aimed to determine the effect of zinc transporter 4 (ZnT4) on testosterone synthesis in male Kunming mice and mouse Leydig cells. The results of this study showed that compared with the zinc normal diet group (Con group), the zinc-deficient diet group (ZnD group) had decreased zinc content and increased ZnT4 expression in testicular tissues, and decreased serum testosterone levels, suggesting that ZnT4 may be involved in Leydig cell injury resulting from a zinc-deficient diet. Subsequently, mouse Leydig cell line TM3 cells were used to analyze the effect of ZnT4 downregulation on TM3 cell proliferation and apoptosis, on testosterone synthesis, and its underlying mechanisms. Here, we show that knockdown of ZnT4 can induce the accumulation of zinc, inhibit the viability, and induce apoptosis in TM3 cells. In addition, knockdown of ZnT4 downregulated testosterone concentration and expression of testosterone synthesis-related proteins steroidogenic acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase/D5-D4 isomerase (3β-HSD) in TM3 cells, while hCG could rescue their levels. We show that it is ZnT4 that plays a role in testosterone production through a mediated PI3K/Akt/mTOR autophagy pathway, whereas mTORC1 complex inhibitor (Rapa) blocks the decrease in testosterone levels caused by ZnT4 downregulation. In conclusion, the above results indicate that ZnT4 plays an important role in regulating testosterone synthesis.