Moxibustion prevents tripterygium glycoside-induced oligoasthenoteratozoospermia in rats via reduced oxidative stress and modulation of the Nrf2/HO-1 signaling pathway.

Oligoasthenoteratozoospermia (OAT) decreases male fertility, seriously affecting the production of offspring. This study clarified the preventive impact of different moxibustion frequencies on OAT and selected the optimal frequency to elucidate the underlying mechanism. An OAT rat model was constructed by gavage of tripterygium glycosides (TGS) suspension. Daily moxibustion (DM) or alternate-day moxibustion (ADM) was administered on the day of TGS suspension administration. Finally, we selected DM for further study based on sperm quality and DNA fragmentation index, testicular and epididymal morphology, and reproductive hormone level results. Subsequently, the oxidative stress (OS) status was evaluated by observing the OS indices levels; malondialdehyde (MDA), 8-hydroxy-deoxyguanosine (8-OHdG), total antioxidant capacity (T-AOC), and total superoxide dismutase (T-SOD) in testicular tissue using colorimetry and enzyme-linked immunosorbent assay. Furthermore, heme oxygenase 1 (HO-1) and nuclear factor erythropoietin-2-related factor 2 (Nrf2) were evaluated using Western blotting. Immunohistochemistry was employed to locate and assess the expression of HO-1 and Nrf2 protein, while quantitative real-time polymerase chain reaction was utilized to detect their mRNA expression. MDA and 8-OHdG levels decreased following DM treatment, while T-SOD and T-AOC increased, suggesting that DM may prevent TGS-induced OAT in rats by decreasing OS in the testis. Furthermore, protein and mRNA expression of Nrf2 and HO-1 in the testis were elevated, indicating that DM may reduce OS by activating the signaling pathway of Nrf2/HO-1. Therefore, DM could prevent OAT in rats via the Nrf2/HO-1 pathway, thereby presenting a promising therapeutic approach against OAT.

Exploring the Potential of Plant Bioactive Compounds against Male Infertility: An In Silico and In Vivo Study.

Infertility is a well-recognized multifactorial problem affecting the majority of people who struggle with infertility issues. In recent times, among infertility cases, the male factor has acquired importance, and now it contributes to approximately half of the infertility cases because of different abnormalities. In the current study, we used natural phytochemicals as potential drug-lead compounds to target different receptor proteins that are involved in the onset of male infertility. A set of 210 plant phytochemicals were docked counter to active site residues of sex hormone-binding globulin, a disintegrin and metalloproteinase 17, and DNase I as receptor proteins. On the basis of binding scores and molecular dynamics simulation, the phytochemicals tricin, quercetin, malvidin, rhamnetin, isorhamnetin, gallic acid, kaempferol, esculin, robinetin, and okanin were found to be the potential drug candidates to treat male infertility. Molecular dynamics simulation showed tricin as a strong inhibitor of all selected receptor proteins because the ligand-protein complexes remained stabilized during the entire simulation time of 100 ns. Further, an in vivo study was designed to evaluate the effect of tricin in male rats with nicotine-induced infertility. It was explored that a high dose of tricin significantly reduced the levels of alanine transaminase, aspartate transaminase, urea, creatinine, cholesterol, triglyceride, and low-density lipoprotein and raised the level of high-density lipoprotein in intoxicated male rats. A high dose of tricin also increased the reproductive hormones (i.e., testosterone, luteinizing hormone, follicle-stimulating hormone, and prolactin) and reduced the level of DHEA-SO4. The phytochemical (tricin, 10 mg/kg body weight) also showed significant improvement in the histo-architecture after nicotine intoxication in rats. From the current study, it is concluded that the phytochemical tricin could serve as a potential drug candidate to cure male infertility.

L-Arginine abrogates maternal and pre-pubertal codeine exposure-induced impaired spermatogenesis and sperm quality by modulating the levels of mRNA encoding spermatogenic genes.

Introduction: Although, codeine has been demonstrated to lower sperm quality; the effects of maternal and prepubertal codeine exposure on male offspring is yet to be reported. In addition, the effect of arginine on codeine-induced decline in sperm quality has not been explored. This study investigated the impact of maternal and prepubertal codeine exposure on spermatogenesis and sperm quality in F1 male Wistar rats to study the effect that codeine may have during recreational use in humans. Also, the effect of arginine supplementation on codeine-induced alteration in spermatogenesis and sperm quality was evaluated. Methods: Female rats were treated with either 0.5 ml distilled water or codeine orally for eight weeks, and then mated with male rats (female:male, 2:1). The F1 male offsprings of both cohorts were weaned at 3 weeks old and administered distilled water, codeine, arginine, or codeine with arginine orally for eight weeks. Results: Prepubertal codeine exposure in rats whose dams (female parents) were exposed to codeine delayed puberty and reduced the weight at puberty. Prepubertal codeine exposure exacerbated maternal codeine exposure-induced reduced total and daily spermatid production, sperm count, sperm motility, and normal sperm form, as well as impaired sperm plasma membrane integrity and increased not intact acrosome and damaged sperm DNA integrity. These perturbations were accompanied by a decrease in mRNA levels encoding spermatogenic genes, testicular testosterone and androgen receptor (AR) concentrations, and upregulation of sperm 8-hydroxydeoxyguanosine (8OHdG). Prepubertal arginine supplementation mitigated codeine-induced alterations. Discussion: This study provides novel experimental evidence that maternal and prepubertal codeine exposure reprogramed spermatogenesis and sperm quality of male FI generation by decreasing mRNA levels encoding spermatogenic genes and AR via oxidative stress-mediated signaling, which was abrogated by prepubertal arginine supplementation.

Guijiajiao (Colla Carapacis et Plastri, CCP) prevents male infertility via gut microbiota modulation.

Male infertility is a significant cause of psychosocial and marital distress in approximately 50% of couples who are unable to conceive, with male factors being the underlying cause. Guijiajiao (Colla Carapacis et Plastri, CCP) is a Traditional Chinese Medicine commonly used to treat male infertility. The present study aimed to investigate the potential mechanisms underlying the preventive effects of CCP on male infertility. An infertile male rat model was established using cyclophosphamide (CTX), and CCP was administered for both treatment and prevention. Fecal microbiota transplantation (FMT) was also performed to explore the role of gut microbiota in the CCP-mediated prevention of male infertility in rats. Sperm motility and concentration were determined using a semi-automatic sperm classification analyzer. Subsequently, histopathological analysis using HE staining was performed to examine the changes in the small intestine and testis. Moreover, the serum levels of lipopolysaccharide (LPS) and testosterone were measured by ELISA. In addition, immunohistochemistry was conducted to detect CD3 expression in the small intestine, while RT-qPCR was employed to assess the expressions of interleukin-1 beta (IL-1ß), cluster of differentiation 3 (CD3), Monocyte chemoattractant protein-1 (MCP-1), and C-X-C motif chemokine ligand 10 (CXCL-10) in the small intestine and epididymis. Finally, gut microbiota was analyzed by 16S rRNA sequencing. CCP improved sperm motility, number, and concentration in CTX-induced infertile male rats. CCP increased the serum testosterone level, inhibited the immune cell infiltration of the intestinal lamina propria, and promoted the aggregation of CD3+ T cells in CTX-induced male infertility rats. CCP also inhibited the expressions of MCP-1, CXCL-10, and IL-1ß in the epididymis of male infertility rats. At the genus level, CTX led to a reduction in the abundance of Lactobacillus, Clostridia_UCG.014, and Romboutsia in the intestinal tract of rats. In contrast, CCP decreased the abundance of Ruminococcus and increased the abundance of Romboutsia in infertile male rats. Additionally, FMT experiments proved that the gut microbiota of CCP-treated rats facilitated testicular tissue recovery and spermatogenesis while also reducing the serum LPS level in infertile male rats. CCP improves the spermatogenic ability of infertile male rats by restoring gut microbiota diversity and inhibiting epididymal inflammation.

Bioactive compounds as potential alternative treatments to prevent cancer therapy-induced male infertility.

About 8-12% of couples experience infertility, with male infertility being the cause in 50% of cases. Several congenital and acquired conditions, including chronic diseases and their treatments, can contribute to male infertility. Prostate cancer incidence increases annually by roughly 3%, leading to an increment in cancer treatments that have adverse effects on male fertility. To preserve male fertility post-cancer survival, conventional cancer treatments use sperm cryopreservation and hormone stimulation. However, these techniques are invasive, expensive, and unsuitable in prepubertal patients lacking mature sperm cells. Alternatively, nutritional therapies enriched with bioactive compounds are highlighted as non-invasive approaches to prevent male infertility that are easily implementable and cost-effective. In fact, curcumin and resveratrol are two examples of bioactive compounds with chemo-preventive effects at the testicular level. In this article, we summarize and discuss the literature regarding bioactive compounds and their mechanisms in preventing cancer treatment-induced male infertility. This information may lead to novel opportunities for future interventions.

Plasma metabolome study reveals metabolic changes induced by pharmacological castration and testosterone supplementation in healthy young men.

Testosterone is a hormone that plays a key role in carbohydrate, fat, and protein metabolism. Testosterone deficiency is associated with multiple comorbidities, e.g., metabolic syndrome and type 2 diabetes. Despite its importance in many metabolic pathways, the mechanisms by which it controls metabolism are not fully understood. The present study investigated the short-term metabolic changes of pharmacologically induced castration and, subsequently, testosterone supplementation in healthy young males. Thirty subjects were submitted to testosterone depletion (TD) followed by testosterone supplementation (TS). Plasma samples were collected three times corresponding to basal, low, and restored testosterone levels. An untargeted metabolomics study was performed by liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) to monitor the metabolic changes induced by the altered hormone levels. Our results demonstrated that TD was associated with major metabolic changes partially restored by TS. Carnitine and amino acid metabolism were the metabolic pathways most impacted by variations in testosterone. Furthermore, our results also indicated that LH and FSH might strongly alter the plasma levels of indoles and lipids, especially glycerophospholipids and sphingolipids. Our results demonstrated major metabolic changes induced by low testosterone that may be important for understanding the mechanisms behind the association of testosterone deficiency and its comorbidities.

Vanillic acid and vitamin C attenuated di-2-ethylhexyl phthalate-induced testicular toxicity in adult male rats.

Abstract: Di-2-ethylhexyl phthalate (DEHP) is an extensively used plasticizer which has raised some concerns about its safety on human health. This study aimed at evaluating the effects of vanillic acid (VA) and vitamin C (VC) supplementation on DEHP-induced testicular toxicity. Thirty-five adult male Wistar rats were randomly divided into 7 groups (A-G) (n = 5) receiving distilled water; 250 mg/kg bw of DEHP only; 30 mg/kg bw of VA and 250 mg/kg bw of DEHP; 30 mg/kg bw of VC and 250 mg/kg bw of DEHP; 30 mg/kg bw of DEHP plus 30 mg/kg bw of VA and 30 mg/kg bw of VC; 30 mg/kg bw of VA only; and 30 mg/kg bw of VC only, respectively. At the end of the experiment, blood was taken from the heart via cardiac puncture and stored, semen was collected from the caudal epididymis for immediate sperm analysis, while the testes were excised and preserved for histological examination and biochemical analysis. The results showed a significant decrease (P < 0.05) in body weights, sperm motility, sperm volume, sperm viability and count, antioxidant levels, and reproductive hormonal levels, with a significant increase (P < 0.05) in sperm morphological defect and lipid peroxidation level in DEHP-only group compared with the control but was ameliorated after VA and VC administration compared to the DEHP-only treated animals. VA and VC supplementation attenuated the toxic effects of DEHP on the testicular functions, morphology, and semen characterization of the experimental adult male Wistar rats. Lay summary: Male infertility is considered when identifiable female causes of infertility are excluded and semen quantity and quality fail to fulfil World Health Organization criteria. From conception through to adulthood, people are exposed to limitless environmental toxicants among which di-2-ethylhexyl phthalate (DEHP) commonly found in personal care products, cosmetics, and medical devices is prevalent. The present study elaborated on the importance of taking antioxidant-rich foods containing vitamin C and vanillic acid, such as those found in various fruits, olives, whole wheat, and cereal grains, in combating infertility caused by environmental toxicants. An experiment was carried out on rats to see the effect of vanillic acid and vitamin C supplementation on preventing DEHP-induced testicular toxicity. The testicles and semen were analyzed from five rats in each treated and control groups. The data led us to conclude that vanillic acid and vitamin C supplementation do have attenuating effects on DEHP-induced testicular toxicity, due to their high antioxidant and anti-inflammatory properties.

Impacts of cadmium on male fertility: Lessons learnt so far.

Cadmium (Cd) is one of the most dangerous heavy metals in the world. Globally, toxicities associated with cadmium and its attendant negative impact on humans and animals cannot be under-estimated. Cd is a heavy metal, and people are exposed to it through contaminated foods and smoking. Cd exerts its deleterious impacts on the testes (male reproductive system) by inducing oxidative stress, spermatogenic cells apoptosis, testicular inflammation, decreasing androgenic and sperm cell functions, disrupting ionic homeostasis, pathways and epigenetic gene regulation, damaging vascular endothelium and blood testes barrier. In association with other industrial by-products, Cd has been incriminated for the recent decline of male fertility rate seen in both man and animals. Understanding the processes involved in Cd-induced testicular toxicity is vital for the innovation of techniques that will help ameliorate infertility in males. In this review, we summed up recent studies on the processes of testicular toxicity and male infertility due to Cd exposure. Also, the usage of different compounds including phytochemicals, and plant extracts to manage Cd reprotoxicity will be reviewed.

Preserving effect of Loboob (a traditional multi-herbal formulation) on sperm parameters of male rats with busulfan-induced subfertility.

OBJECTIVE: Male infertility secondary to exposure to gonadotoxic agents during reproductive age is a concerning issue. The aim of this experimental study was to determine the effect of Loboob on sperm parameters. METHODS: 55 healthy rats were selected, weighted and divided into five groups consisting of 11 rats each. The control group received no medication. Rats in Treatment Group 1 received 10mg/kg Busulfan and rats in Treatment Groups 2, 3, and 4 received 35,70 and 140 mg/kg Loboob respectively in addition to 10mg/kg Busulfan. Finally, the sperm parameters and weights of the rats were compared using the Kolmogorov-Smirnov, non-parametric Kruskal-Wallis, and Dunn-Bonferroni tests. RESULTS: All sperm parameters and weights were significantly decreased among rats receiving Busulfan. All dosages of Loboob were effective to enhance the motility of slow spermatozoa, while only in the rats given 70 and 140 mg/kg of Loboob saw improvements in progressively motile sperm percentages (0.024 and 0.01, respectively). Loboob at a dosage of 140mg/kg improved sperm viability. It did not improve normal morphology sperm or decrease immotile sperm counts. Loboob did not affect mean rat weight. CONCLUSIONS: Loboob offered a dose-dependent protective effect on several sperm parameters in rats with busulfan-induced subfertility.

Ameliorative Potential of Hydroethanolic Leaf Extract of Parquetina nigrescens on d-Galactose-Induced Testicular Injury.

BACKGROUND: There is an increasing need for botanicals to be used as an alternative and complementary medicine in the management of male infertility. Male infertility has been a major health/social challenge to people all over the world. This study, therefore, investigated the ameliorative potential of hydroethanolic leaf extract of Parquetina nigrescens (HELEPN) against d-galactose-induced testicular injury. METHODS: Thirty male Wistar rats were randomly allotted into six groups (n = 5). Group I (Normal control), Group II (300 mg/kg b.w. d-galactose), Group III and IV (250 and 500 mg/kg b.w. HELEPN, respectively), Group V and VI (both received 300 mg/kg b.w. of d-galactose with 250 and 500 mg/kg b.w of HELEPN, respectively). d-galactose administration started two weeks prior to HELEPN treatment which lasted for six weeks. All assays were carried out using established protocols. RESULTS: Administration of HELEPN at 250mg/kg and 500mg/kg concomitantly with d-galactose improved paired and relative testicular weights, levels of gonadotropins (LH and FSH) and testosterone, and poor sperm quality. HELEPN treatment reduced the levels of oxidative stress biomarkers (MDA, 8-OHDG, and AGEs) and inflammatory response (TNF-alpha and NO) to normal, as well as restoring the reduced activities of antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase). In addition, HELEPN treatment mitigated testicular DNA fragmentation and down-regulated caspase 3-activities. HELEPN at 500 mg/kg was observed to have the greatest ameliorative effect. CONCLUSION: HELEPN protects against d-galactose-induced testicular injury through antioxidative, anti-inflammatory, and antiapoptotic mechanisms.

Xiaokang Liuwei Dihuang decoction ameliorates the immune infertility of male rats induced by lipopolysaccharide through regulating the levels of sex hormones, reactive oxygen species, pro-apoptotic and immune factors.

Male immune infertility is a kind of disease that damages family life and happiness. The development of novel methods treating male immune infertility is of great significance. This study aimed to investigate the therapeutic effects of Chinese medicine Xiaokang Liuwei Dihuang decoction on immune infertility of male rats and explored the involved mechanisms. Model rats were established by lipopolysaccharide (LPS) injection. Anti-sperm antibody (AsAb) was detected by ELISA assay and testicular cell apoptosis was evaluated by TUNEL staining to verify the successful model establishment and screen suitable doses of Xiaokang Liuwei Dihuang decoction. Thirty rats were then divided into five groups (n = 6 per group): Control, LPS, Xiaokang Liuwei Dihuang decoction (15.12 g/kg, 30.24 g/kg and 45.36 g/kg). Results of HE staining showed that compared with LPS group, Xiaokang Liuwei Dihuang decoction treatments gradually improved the morphology of seminiferous tubules and elevated the number of spermatogenic cells as the doses increased. The sperm number and the levels of testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) in the serum of 15.12 g/kg, 30.24 g/kg and 45.36 g/kg Xiaokang Liuwei Dihuang decoction groups were much higher than those in LPS group. Results of TUNEL staining, ELISA assay and western blot showed that compared with LPS group, the testicular cell apoptosis and the levels of interleukin 1ß (IL-1ß), tumor necrosis factor α (TNF-α), AsAb, malondialdehyde (MDA) and toll-like receptor 2 (TLR2) in the testicular tissue significantly decreased in three Xiaokang Liuwei Dihuang decoction groups. Compared with LPS group, Bax expression in the 30.24 g/kg and 45.36 g/kg Xiaokang Liuwei Dihuang decoction groups was significantly down-regulated as well. In conclusion, Xiaokang Liuwei Dihuang decoction might ameliorate the immune infertility of male rats induced by LPS through regulating the levels of sex hormones, reactive oxygen species, pro-apoptotic and immune factors.

Photobiomodulation Therapy Improves Spermatogenesis in Busulfan-Induced Infertile Mouse.

About 50% of infertility is caused by men. This study aimed to investigate the efficiency of photobiomodulation on spermatogenesis in a busulfan-induced infertile mouse as a testicular degeneration treatment. Thirty-two adult NMRI male mice were divided into 4 groups: control, busulfan, PBMT 0.03 J/cm2, and laser 0.2 J/cm2. In the study, azoospermia was induced by busulfan as a testicular degeneration, and then, they were treated using photobiomodulation therapy at 0.03 J/cm2 and 0.2 J/cm2 energy densities. Sperm parameters, stereological analysis, serum testosterone levels, together with SDH activity, MDA production oxidized as a marker for lipid peroxidation, glutathione (GSSG) and glutathione (GSH), mitochondrial membrane permeability (MMP), reactive oxygen species (ROS) production, and ATP production as well as TUNEL assay were assessed. Photobiomodulation therapy with 0.03 J/cm2 energy densities group revealed a significant increase the testosterone hormone level and spermatogenic cells with the reduction of apoptotic cells and marked increase in GSH, ATP, and SDH levels and decrease the levels of MDA and ROS production in the busulfan-induced mice when compared with the control and sham groups. In conclusion, the photobiomodulation therapy (0.03 J/cm2 energy density) may provide benefits on the spermatogenesis following busulfan injection and might be an alternative treatment to the patients with oligospermia and azoospermia in a dose-dependent manner.

Effect of Rourea coccinea on ethanol-induced male infertility in Wistar albino rats.

Ethanol consumption is a risk factor of male infertility. The use of medicinal plants offers an alternative for the treatment of male infertility in developing countries. This study aimed to evaluate the Rourea coccinea effect on ethanol-induced male infertility in Wistar rats. Twenty-five (25) male Wistar rats were randomised into five groups of five rats and treated by oesophageal gavage over a 28-day period. Group 1 (negative control) received distilled water; Group 2 (positive control) received 30% ethanol at 7 mg/kg body weight; Group 3 (reference control) received 30% ethanol co-treated with the reference drug, clomiphene citrate; Groups 4 and 5 (test groups) received 30% ethanol co-treated with Rourea coccinea hydro-ethanolic extract at 200 and 400 mg/kg respectively. Testosterone hormone, sperm parameters and testicular histopathology were evaluated. Ethanol treatment induced a significant reduction (p < .05) in sperm count, motility, viability and a significant increase in sperm abnormalities because of the significant decrease (p < .05) in testosterone levels. These data correlate with the alterations observed in the seminiferous tubule on histopathological examination of the testes. However, co-treatment of ethanol with Rourea coccinea extract or the reference drug restored the ethanol-induced toxic effects on the reproductive organs, sperm profile and testosterone level.

Modified MYOMI-14 Korean herbal formulations have protective effects against cyclophosphamide-induced male infertility in mice.

Korean herbal formulation, MYOMI-14, has been reported to improve the idiopathic male infertility condition with poor semen. In this study, four MYOMI formulations were modified from MYOMI-14 by reducing the number of constituents. We investigated the therapeutic effect of MYOMI formulations on cyclophosphamide-induced male infertility using mice model. Cyclophosphamide treatment significantly decreased body weight, testicular weight, sperm count, normal-shaped sperm rate and sperm motility compared to untreated control group, whereas MYOMI formulations restore the cyclophosphamide-induced dysfunction, as determined by increased sperm count and motility, and decreased abnormally shaped spermatozoa. In addition, treatment with MYOMI formulations reduced cyclophosphamide-induced apoptosis of germ cells and oxidative stress. MYOMI-treated mice also showed improved spermatogenesis as shown by the increased expression of spermatogenesis-related genes, as cAMP-responsive element modulator (CREM) and cAMP response element-binding (CREB) protein. Among the MYOMI formulations, MYOMI-7 showed better results in terms of recovering CP-induced damages to testis and improving the fertility. Taken together, this study is expected to make significant contribution to the literature by exploring various formulations that reduced constituents of MYOMI-14, a Korean herbal medicine, in treating CP-induced male infertility.

Semen Cuscutae-Fructus Lycii improves spermatogenic dysfunction by repairing the blood-testis barrier in rats according to in silico and in vitro methods.

ETHNOPHARMACOLOGICAL RELEVANCE: Semen Cuscutae and Fructus Lycii (SC-FL) is a commonly used herbal pair for male infertility treatment. Studies have found that the mechanism of SC-FL treatment may be related to repairing the blood-testis barrier (BTB). The application of network pharmacology can be used to explore the correlation between medicines and diseases and predict the potential pharmacological mechanisms of SC-FL. AIM OF THE STUDY: This study aimed to explore the specific effects and mechanisms of SC-FL in repairing the BTB and initially revealed the mechanism of Chinese medicine treating male infertility through network pharmacology and animal experiments. MATERIALS AND METHODS: We searched databases using the network pharmacology method and performed mass spectrometry analysis. We analyzed and predicted the active ingredients, targets and key pathways of SC-FL in male infertility treatment. Then, we designed animal experiments to verify the results. Thirty-six Sprague-Dawley rats were randomly divided into the normal control group (NC group), spermatogenic dysfunction group (SD group) and SC-FL treatment group (SCFL group). Glucosides of Tripterygium wilfordii Hook. F (GTW) (40 mg/kg/d) was administered for 4 weeks to generate a spermatogenic dysfunction model. The rats in the SCFL group were given the SC-FL suspension (6 g/kg/d) daily. After 4 weeks of treatment, we detected the sperm quality of each group of rats and observed the cell morphology. Western blotting and qRT-PCR were used to detect the expression of BTB-related proteins in testicular tissues. RESULTS: 213 chemical ingredients of SC and FL were retrieved from the TCMSP database, and 54 effective chemical ingredients were obtained. Mass spectrometry analysis showed the above results were credible. Then, we identified 44 potential targets for the treatment of male infertility, and we plotted a network diagram of the interaction network between the core targets and a diagram of herbal medicine-active ingredient-target-disease interactions. The target genes were enriched according to biological functions, and 22 biological processes, 49 cellular components, 1487 molecular functions, and 122 signaling pathways were obtained. The results of the animal experiments showed that the sperm concentration and motility of the SCFL group were significantly improved compared with those of the SD group. Compared with those in the SD group, the structure and morphology of the Sertoli cells and seminiferous tubules of rats in the SCFL group improved, and the number of spermatogenic cells increased significantly. Western blotting and qRT-PCR results showed that compared with that in the SD group, the expression of p38 MAPK decreased significantly, and the expression of c-Jun, Occludin, ZO-1 and connexin 43 increased significantly in the SCFL group. CONCLUSION: We predicted that the active ingredients of SC-FL can treat male infertility by interacting with the core targets JUN, IL6, MAPK1, TP53, MYC, CCND1, AR, EGF, FOS, and MAPK8, and the possible mechanism is related to the MAPK signaling pathway. SC-FL can regulate the MAPK pathway and affect the expression of Occludin, ZO-1 and connexin 43 to repair damaged BTB and improve spermatogenic dysfunction induced by GTW, which may be one of the possible mechanisms.

Leaf and Fruit Methanolic Extracts of Azadirachta indica Exhibit Antifertility Activity on Rats' Sperm Quality and Testicular Histology.

BACKGROUND: The world's population is still growing, having an impact on the environment and the economic growth of developing countries; so that, there is a particular interest in the development of new fertility control methods, focused on male contraception. OBJECTIVE: The objective of this study was to evaluate the effect of methanolic extracts of leaf and fruit of Azadirachta indica on sperm quality and testicular histology of Long Evans rats. METHODS: Antifertility effects of a methanolic leaf and fruit extracts of A. indica on 24 male rats were investigated. The animals were randomly divided into two control groups and four treatment groups (n=4). Doses of the leaf and fruit extract were given at concentrations of 100 and 200 µg mL-1. RESULTS: A significant decrease in the viability of sperm cells was observed. The leaf extract at a concentration of 200 µg mL-1 inhibited cell viability compared to the negative control (p< 0.001). The percentage of abnormal cells in leaf extract was shown in 100 and 200 µg mL-1, the conditions at which a higher percentage of morphological irregularities of observed (15% and 16% respectively). The results show that there was cellular detachment in the seminiferous epithelium in the experimental groups treated with methanolic extracts. Sperm death was observed without decreasing the number of sperm. CONCLUSION: The methanolic extracts of Azadirachta indica have a modulating effect on the spermatogenesis of experimental rats through sperm morphological alterations.

Chemical and Nutraceutical Studies on Infertility of Albino Rats Induced by Cadmium Chloride.

BACKGROUND AND OBJECTIVE: Infertility in couples is rated one in every eight couple worldwide which affects 15% of couples and a male factor is found to be solely responsible or in conjunction with a female factor in 50% of cases. The natural chemicals found in rocca and red cabbage leaves breakdown into compounds like indole-3-carbinol, which has anti-cancer property. Flavonoids of the crop have good therapeutic potential in inflammation and pain. Meanwhile, this investigation aimed to evaluate the effect of rocca leaves and red cabbage leaves on male infertility rats. MATERIALS AND METHODS: Thirty-six adult male Sprague Dawley rats were divided into six groups. Group 1: Normal rats fed on basal diet as control negative (C-), Group 2: Control positive C+, in which infertility rats were fed on basal diet. Group 3: Infertility rats fed on basal diet and 5% rocca leaves. Group 4: Infertility rats fed on basal diet and 10% rocca leaves. Group 5: Infertility rats fed on basal diet and 5% red cabbage leaves. Group 6: Infertility rats fed on basal diet and 10% red cabbage leaves. At the end of experiment, after 28 days of feeding, all serum samples were analyzed for biochemical parameters. RESULTS: Injection with cadmium chloride caused a significant increase in the level of glucose, urea, creatinine, uric acid, AST, ALT, ALP, total cholesterol, triglycerides, LDLc, VLDLc, AI, Glob, TB, IB, DB and LH hormone while a significant decrease was recorded in HDLc, testosterone, FSH hormones, TP and Alb. Meanwhile, in infertility rats then treated with rocca leaves 5 and 10% and red cabbage leaves at the same doses 5 and 10% caused significant improvement in all tested parameters. CONCLUSION: The obtained results demonstrated that rocca leaves and red cabbage leaves had significant improvement in testosterone, Follicle-stimulating hormone, luteinizing hormone, total protein, albumin and lipids profile in cadmium chloride induced infertility in rats.

Evaluation of male infertility treatment following Rhus coriaria extract administration on rats exposed to morphine.

Morphine is the most common analgesic drug that is widely used in post-operative interventions. This drug causes free radical accumulation leading to spermatogenesis failure. Antioxidant agents like Sumach (Rhus coriaria) neutralize cellular free radicals. In this study, the properties of antioxidative, modulative of inflammatory cytokines, and apoptotic genes following Sumach extract administration on morphine-induced fertility destruction in male Wistar rats was evaluated. Sixty-four animals were grouped (n = 8) including; 1: control, 2: morphine, 3-5: Sumach (200, 400, 800 mg/kg), and 6-8: morphine + Sumach. Hydroalcoholic extract of Sumach seeds was prepared. Treatments with Sumach extract were applied orally and intraperitoneally daily for 8 weeks. The P53, Bcl2 and caspase-3 genes expression were measured by real-time PCR. Cytokines involved in inflammation were evaluated by ELISA. Sperm parameters, total antioxidant capacity (TAC), testosterone, and germinal layer height (GLH) were assessed. All parameters (investigated in this study) in Morphine group reduced significantly than the control group (P ˂ 0.01) (except P53 and caspase-3 genes expression and inflammatory cytokine which were improved). All factors in Sumach and Sumach + Morphine groups were significantly enhanced compared to the Morphine group (P ˂ 0.01) (except P53 and caspase-3 genes expression and inflammatory cytokine which were declined). Morphine disrupted the physiological function of male fertility system. Besides, all doses of Sumach showed no therapeutic changes compared to the control group. Sumach with anti-infertility features compensates the toxic effect of Morphine administration.

Bisphenols and Male Reproductive Health: From Toxicological Models to Therapeutic Hypotheses.

Bisphenols, and in particular bisphenol A (BPA), have been widely used for the production of plastic manufacts in the last 50 years. Currently, BPA is present in a variety of daily use polycarbonate plastics and epoxy resins, and dietary ingestion is considered the main route of human exposure. Accordingly, BPA is the chemical pollutant with the widest exposure in humans, involving nearly 90% of general population, according to recent studies. Concerns about BPA effects on human health date back to 1930s, when severe impact on male sexual development was suggested. Now, the acknowledged biological effects of BPA are various. In regard to human fertility, BPA has been shown to disrupt hormone signaling even at low concentrations. Results from human epidemiological studies have reported BPA interference with follicle stimulating hormone, inhibin B, estradiol, testosterone levels, and sexual function in male subjects. Moreover, recent studies have reported an association between BPA levels and reduced sperm concentration, motility, normal morphology, sperm DNA damage, and altered epigenetic pattern, resulting in trans-generational legacy of BPA effects. In this review, the recognized effects of BPA on male reproductive health are described, from the most recent issues on experimental models to epidemiological data. In addition, the very recent interest about the use of nutraceutical remedies to counteract BPA effects are discussed.

Un-riped fruit pods of Prosopis cineraria (L.) Druce ameliorates Cisplatin therapy-induced partial testicular atrophy in male Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Prosopis cineraria (L.) Druce is a plant that is widely found in dry parts of India. The unripe fruit pod has a very specific traditional claim of treating male infertility and increasing sperm volume and count. AIM: The present work was endeavored to investigate the long-standing traditional claim of P. cineraria on meliorating male fertility. The study focussed on cancer therapy-induced male infertility and curative effect of the extract with an appraisal on any possible revitalizing effects on sperm count, morphology, motility, and viability combined with hormonal and histopathological investigations. MATERIALS AND METHODS: Male Wistar rats were used for the study. Two different doses of 400 mg/kg/d and 800 mg/kg/d (both p.o.) of the Hydroalcoholic extract were chosen as test dose while Clomiphene (25 mg/kg/d; p.o.) treatment served as standard treatment. Animals were initially injected with cisplatin (1 mg/kg/d; i.p.) for 15 days and the drug treatment was begun at the 16th day and continued till 43rd day (28 days treatment). Later all male animals got cohabited with female animals in the ratio 1:3. On confirmation of mating, female animals were isolated. Male animals were euthanized on batches. Testis and epididymis were weighed and homogenized. Sperm count, motility, morphology, viability, and headcount. The serum collected was evaluated for serum FSH, LH, and testosterone levels. On day Gestational day 15, gravid uterus observations were calculated to evaluate male and female fertility parameters. RESULTS: There were statistically significant improvements (p < 0.001) in sperm motility, sperm count, sperm viability, and improved morphological features. The same pace was also noticed in testosterone, FSH and LH levels in serum and LPO, CAT, GSH, GPx and SOD in testicular tissues. The extract treated male animals produced better and healthy litter compared to cisplatin-treated animals with less pre- and post-implantation loss. CONCLUSION: Consolidating the results seen, the extract ameliorated the testicular toxicity caused by cisplatin in a dose-dependent manner. Further insight and evaluation of the phytochemicals of the pods should be performed to bring up commercial viability.