Objective: Testicular fat deposition has been reported to affect animal reproduction. However, the underlying mechanism remains poorly understood. The present study explored whether sperm meiosis and testosterone synthesis contribute to mouse testicular fat deposition-induced reproductive performance. Methods: High fat diet (HFD)-induced obesity CD1 mice (DIO) were used as a testicular fat deposition model. The serum hormone test was performed by agent kit. The quality of sperm was assessed using a Sperm Class Analyzer. Testicular tissue morphology was analyzed by histochemical methods. The expression of spermatocyte marker molecules was monitored by an immuno-fluorescence microscope during meiosis. Analysis of the synthesis of testosterone was performed by real-time polymerase chain reaction and reagent kit. Results: It was found that there was a significant increase in body weight among DIO mice, however, the food intake showed no difference compared to control mice fed a normal diet (CTR). The number of offspring in DIO mice decreased, but there was no significant difference from the CTR group. The levels of follicle-stimulating hormone were lower in DIO mice and their luteinizing hormone levels were similar. The results showed a remarkable decrease in sperm density and motility among DIO mice. We also found that fat accumulation affected the meiosis process, mainly reflected in the cross-exchange of homologous chromosomes. In addition, overweight increased fat deposition in the testis and reduced the expression of testosterone synthesis-related enzymes, thereby affecting the synthesis and secretion of testosterone by testicular Leydig cells. Conclusion: Fat accumulation in the testes causes testicular cell dysfunction, which affects testosterone hormone synthesis and ultimately affects sperm formation.
We reported previously that the administration of Korean red ginseng water extract (KRG-WE) protected the guinea pig testis against damage induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (a potent endocrine disruptor). We also found that crude saponin from ginseng was the active ingredient responsible for this protection. Here, we examined the biological role of KRG-WE in an animal model of age-induced dysfunction of spermatogenesis. Twenty-four male Sprague-Dawley (six 2-month-old and eighteen 12-month-old) rats were used. The young and old control groups received only vehicle. The ginseng saponin (GS)- and KRG-WE-treated groups received GS (40 mg/kg body weight/day) and KRG-WE (200 mg/kg body weight/day), respectively, for 4 months. The number of cells, Sertoli cell index, Johnsen's score, and sex hormone levels decreased significantly with age. However, the administration of KRG-WE and GS markedly improved the number of germ cells, seminiferous tubular size, and Johnsen's score in the old rats. Ginseng produced a distinct testicular histological improvement in old rats. KRG-WE and GS elevated testosterone levels, while attenuating the aberrant increase in follicle stimulating hormone and luteinizing hormone levels. Sperm kinematics evaluated by a computer-assisted sperm analyzer demonstrated improvement in the percentage of motile sperm, progressive sperm motility, and curvilinear velocity associated with sperm quality, supporting the beneficial role of red ginseng in senile spermatogenesis. Overall, the total water extract had a more potent effect than the corresponding saponin fraction. In conclusion, Korean red ginseng rejuvenated age-induced testicular dysfunction. Additionally, the total water extract was more potent than the corresponding saponin fraction.
Objective: These studies were undertaken to evaluate the effects of the different administration duration of Morindae Radix extract solution on spermatogenic abilities such as concentration, motility and morphological normality of sperm from the testes and the activities of sperm hyaluronidase. Materials and Method: We used 8-week-old ICR mice and administered 0.3mg/g extract solution of Morindae Radix once a day for 30, 60, 90 and 120 days. The control group was administered normal saline in the same way and duration. We examined the number of total, motile and normal sperm from the cauda epididymis. We also compared the testicular tissue, especially seminiferous tubules, between the control and treated groups by histochemical methods. Finally, we observed the difference of sperm hyaluronidase activities between the control and treated groups. Results: Significant administration duration-dependent differences were observed in the concentration of total sperm, motility and normality of spermatozoa of the Morindae Radix extract solution administered groups compared to the control group. In the histological analysis of the testicular tissues, the enlargement of testicular lobe diameter and apparent vasculogenesis between testicular lobes were observed in the Morindae Radix extract solution administered groups compared to the control group. Also, the activity of hyaluronidase was significantly increased in the Morindae Radix extract solution administered groups compared to the control group. Conclusions: This study shows that the beneficial effect of Morindae Radix extract solution on the concentration, motility and morphology of sperm, the testicular tissues and the activities of sperm hyaluronidase increased the greater the duration the mice were administered it. We suggest that Morindae Radix may be useful for the treatment of male sexual dysfunction and infertility.
Samir, Shereen M.;Elalfy, Mahmoud;El Nashar, Eman Mohamad;Alghamdi, Mansour A.;Hamza, Eman;Serria, Mohamed Saad;Elhadidy, Mona G.
The Korean Journal of Physiology and Pharmacology
/
v.25
no.4
/
pp.341-354
/
2021
Cardamonin (CARD) is a chalconoid with anti-inflammatory and antioxidant properties, and it is present in several plants. We sought to explore whether CARD exerts any positive effects against hyperglycemia-induced testicular dysfunction caused by type 2 diabetes and aimed to identify its possible intracellular pathways. Adult male rats were subdivided into six groups: control, CARD, diabetic (DM), DM + glibenclamide (GLIB), DM + CARD and DM + GLIB + CARD. Type 2 DM induced a significant increase in blood glucose and insulin resistance, along with diminished serum insulin, testosterone and gonadotropins levels, which were associated with the impairment of key testicular androgenic enzymes and cellular redox balance. Administration of CARD at a dose of 80 mg/kg for 4 weeks effectively normalized all of these alterations, and the improvement was confirmed by epididymal sperm analysis. After treatment with CARD, the pathological changes in spermatogenic tubules were markedly improved. Significantly, CARD upregulated testicular glucose transporter-8 (GLUT-8) expression and had inhibitory effects on elevated autophagy markers and caspase-3 immunoreactive cells. Furthermore, our results revealed that CARD was able to attenuate damage via activation of Nrf2 through the p62-dependent degradation of testicular anti-Kelch-like ECH-associated protein-1 (Keap-1). In conclusion, this study suggests that CARD provides protection against diabetic stress-mediated testicular damage. The use of CARD with conventional anti-diabetic therapy was associated with improved efficacy compared with conventional therapy alone.
Elna Owembabazi;Pilani Nkomozepi;Tanya Calvey;Ejikeme Felix Mbajiorgu
Anatomy and Cell Biology
/
v.56
no.2
/
pp.236-251
/
2023
Alcohol consumption alongside combination antiretroviral therapy (cART) has attracted research interest, especially because of increasing male infertility. This study investigated the combined effects of alcohol and cART on testicular morphology, biomarkers of oxidative stress, inflammation, and apoptosis. Rats, weighing 330-370 g, were divided into four groups of six animals each; control, alcohol treated (A), cART, and alcohol plus cART treated (A+cART). Following 90 days treatment period, animals were euthanized, testis extracted, and routinely processed for histology and immunohistochemical analysis. Significantly decreased epithelial area fraction, increased luminal and connective tissue area fractions, and reduction of epithelial height and spermatocyte number, were recorded in the treated groups compared to control. Extensive seminiferous epithelial lesions including widened intercellular space, karyolysis, and sloughing of germinal epithelium were recorded in all the treated groups. Furthermore, upregulation of inducible nitric oxide synthase and 8-hydroxydeoxyguanosine, interleukin-6, and caspase 3 recorded in treated animals, was more significant in A+cART group. Also, the levels of interleukin-1β and tumor necrosis factor-α were more elevated in A and cART treated groups than in A+cART, while MDA was significantly elevated in cART and A+cART treated groups compared to control group. Altogether, the results indicate testicular toxicity of the treatments. It is concluded that consuming alcohol or cART induces oxidative stress, inflammation, and apoptosis in testis of rats, which lead to testicular structural and functional derangements, which are exacerbated when alcohol and cART are consumed concurrently. The result will invaluably assist clinicians in management of reproductive dysfunctions in male HIV/AIDS-alcoholic patients on cART.
Brassica oleracea var. italica (broccoli) is a type of cabbage that contains vitamins, minerals, and phytochemicals. Consequently, it is used as a potential nutraceutical source for improving human health by reducing oxidative stress and inflammatory responses. Here, the effects of broccoli sprout extract (BSE) on the inflammatory response were investigated through lipopolysaccharide (LPS)-induced inflammatory mouse models. First, we found that the BSE obviously reduce NO production in RAW 264.7 cells in response to LPS stimulation in in vitro study. Pretreatment with BSE administration improved sperm motility and testicular cell survivability in LPS-induced endotoxemic mice. Additionally, BSE treatment decreased the levels of the pro-inflammatory cytokines TNF-a, IL-1β, and IL-6, and COX-2 in testis of LPS-induced endotoxemic mice models. In conclusion, BSE could be a potential nutraceutical for preventing the excessive immune related infertility.
Inflammaging in male reproductive organs covers a wide variety of problems, including sexual dysfunction and infertility. In this study, the beneficial effects of cordycepin (COR), isolated from potential medicinal fungi Cordyceps militaris, in aging-associated testicular inflammation and serum biochemical changes in naturally aged rats were investigated. Male Sprague Dawley rats were divided into young control (YC), aged control (AC), and COR (5, 10, and 20 mg/kg) treated aged rat groups. Aging-associated serum biochemical changes and inflammatory parameters were analyzed by biochemical assay kits, Western blotting, and real-time RT-PCR. Results showed a significant (p < 0.05) alteration in the total blood cell count, lipid metabolism, and liver functional parameters in AC group when compared with YC group. However, COR-treated aged rats ameliorated the altered biochemical parameters significantly (p < 0.05 and p < 0.01 at 5, 10, and 20 mg/kg, respectively). Furthermore, the increase in the expression of inflammatory mediators (COX-2, interleukin (IL)-6, IL-1β, and tissue necrosis factor-alpha) in aged rat testis was significant (p < 0.05) when compared with YC group. Treatment with COR at 20 mg/kg to aged rats attenuated the increased expression of inflammatory mediators significantly (p < 0.05). Mechanistic studies revealed that the potential attenuating effects exhibited by COR in aged rats was mediated by regulation of NF-κB activation and MAPKs (c-Jun N-terminal kinase, extracellular signal-regulated kinase 1/2, and p38) signaling. In conclusion, COR restored the altered serum biochemical parameters in aged rats and ameliorated the aging-associated testicular inflammation proving the therapeutic benefits of COR targeting inflammaging-associated male sexual dysfunctions.
Objective: Sleep deprivation (SD) is a common problem in today's stressful lifestyle and have physiological consequences, including reproductive dysfunction and infertility. As an antioxidant, olive oil may be effective in reducing testicular and spermatological damage by decreasing the production of free radicals. Methods: This study investigated the effects of olive oil on sperm quality and testicular structure using stereological methods to assess rats with SD. Results: When comparing SD group to grid floor+distilled water (GR) group, we found that the sperm count and motility, as well as the percentage of slow progressive sperm was significantly lower in SD group (p<0.05), but the percentage of immotile sperm was higher (p<0.01). However, no improvement was observed in sperm count or motility after concomitant treatment of SD group with olive oil. Stereological examinations revealed no significant change in the total volumes of the seminiferous tubules, interstitial tissue, and germinal epithelium in the study groups. Conversely, the total number of testicular cell types was significantly lower in SD group than in GR group. Although the total number of Sertoli and Leydig cells was significantly higher in the S +olive oil group than in the untreated SD group, no significant difference in the total number of other testicular cell types was observed between the two groups. Conclusion: SD potentially induced structural changes in testis that affected sperm count and motility. However, olive oil only improved the total number of Sertoli and Leydig cells in the animals with SD and did not improve sperm count and motility.
Young-Joo, Yi;Malavige Romesha, Chandanee;Dong-Won, Seo;Jung-Min, Heo;Min, Cho;Sang-Myeong, Lee
Korean Journal of Agricultural Science
/
v.48
no.4
/
pp.935-944
/
2021
It has been suggested that bisphenol A (BPA), a known endocrine disruptor, interferes with the endocrine system, causing reproductive dysfunction. Recently, BPA has been found in waste water due to incomplete sewage purification, possibly threatening health through its ingestion via tap water. In this study, young male mice (6 - 7 weeks old) were administered water containing BPA (50 mg·kg-1) for four weeks, while control mice consumed water without BPA. Serum, epididymal spermatozoa and testicular sections were assessed after sacrificing the mice on day 28. No significant differences were obtained between the groups in the body, testis and seminal vesicle weights. However, the epididymal sperm motility and count levels were significantly reduced in BPA-fed mice. Significantly higher hepatotoxicity levels were also observed in mice ingesting BPA as compared to the control mice. The level of serum testosterone was reduced, and testicular sections revealed incomplete and irregular spermatogenesis in BPA-ingested mice. The sperm proteasomal-proteolytic activity level has been implicated in sperm function and is measured in motile spermatozoa using fluorometric substrates. High ubiquitin C-terminal hydrolase activity levels were observed in the control mice without BPA. During a mating trial, a low pregnancy rate (71.4%) was observed in females mated with males who had consumed BPA (100% in the control mice). Overall, BPA adversely affected spermatogenesis and quality, as indicated by decreased sperm motility, concentration and serum testosterone levels, resulting in reduced fertility competence.
Kim, Kang-Hyeon;Shin, In-Sik;Lim, Jeong-Hyeon;Kim, Sung-Hwan;Park, Na-Hyeong;Moon, Chang-Jong;Kim, Sung-Ho;Shin, Dong-Ho;Kim, Jong-Choon
Toxicological Research
/
v.25
no.4
/
pp.203-207
/
2009
Present study was conducted to investigate potential effects of epichlorohydrin on testicular and epididymal function in male rats. The test chemical was administered to adult male rats by gavage at dose levels of 0, 3.125, 12.5, and 50 mg/kg/day for 7 days. Testicular and epididymal function were assessed by measurement of reproductive organ weight, testicular spermatid count, epididymal sperm count, motility and morphology, and histopathology in rats. At 50 mg/kg, a decrease in the sperm motility and an increase in the incidence of sperm abnormalities were observed. Histopathological examinations revealed an increase in the incidence of histopathological changes including cell debris in the ducts, vacuolization of the epithelial cells, oligospermia, and epithelial disruption in the proximal caput epididymidis. At 12.5 mg/kg, an increase in the incidence of histopathological changes of the epididymidis was found. There were no treatment-related effects at 3.125 mg/kg. These results show that 7-day repeated oral administration of epichlorohydrin to male rats results in adverse effects on sperm motility, sperm morphology, and epididymal histology at $\geq$ 12.5 mg/kg/day.
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