Trends in semen parameters of infertile men in South Africa and Nigeria.

There are conflicting reports on trends of semen parameters from different parts of the globe. However, in recent times there is dearth of information on the trend in Sub-Saharan countries. Therefore, in this study we aimed at determining the trends in semen parameters in Nigeria and South Africa between 2010 and 2019. A retrospective study of semen analyses of 17,292 men attending fertility hospitals in Nigeria and South Africa in 2010, 2015 and 2019. Patients who had undergone vasectomy and those who had a pH less than 5 or greater than 10 were excluded from this study. The following variables were assessed: ejaculate volume, sperm concentration, progressive motility, total progressively motile sperm count (TPMSC), total sperm count, and normal sperm morphology. Between 2010 and 2019, significant trends of decreasing values were observed in normal sperm morphology (- 50%), and the ejaculatory volume (- 7.4%), indicating a progressive deterioration of the values in both countries. In Nigeria, there were significant decreases in progressive motility (- 87%), TPMSC (- 78%), and sperm morphology (- 55%) between 2010 and 2019 (P < 0.001). Spearman`s rank correlation revealed significant negative associations between age and morphology (ρ = - 0.24, P < 0.001), progressive motility (ρ = - 0.31. P < 0.001), and TPMSC (ρ = - 0.32, P < 0.001). Patients in South Africa were younger than those from Nigeria, with also a significantly higher sperm morphology, sperm concentration, progressive motility, total sperm count and TPMSC. Our findings provide a quantitative evidence of an alarming decreasing trend in semen parameters in Nigeria and South Africa from 2010 to 2019. It also proves that astheno- and teratozoospermia are the leading causes of male infertility in these regions. In addition to this, it also shows empirically that semen parameters decrease with advancement in age. These findings are the first report of temporal trends in semen parameters in Sub-Saharan countries, necessitating a thorough investigation on the underlying factors promoting this worrisome decline.

The impact of dolutegravir-based combination antiretroviral therapy on the spermatozoa and fertility parameters of men living with human immunodeficiency virus.

The factors responsible for this reported fertility decline among human immunodeficiency virus (HIV) positive men is yet to be determined. This study is aimed at investigating the impact of HIV or combination antiretroviral therapy (cART) on sperm cells, reproductive hormones, oxidative stress markers, apoptosis, and sperm DNA fragmentation of men living with HIV. Twenty-one men living with HIV gave their written informed consent to participate in this study. Only 11 of the participants successfully donated blood and semen before and after 3 months of their treatment with cART. Semen, reproductive hormones, oxidative stress biomarkers, and DNA fragmentation were analysed. Data were subjected to Wilcoxon matched pairs signed rank test (ethical approval: CMUL/HREC/09/19/614). There was a significant decrease in viral load of HIV (p < 0.01), and a marked increase in progressive and total sperm motility. Total sperm count, morphology, and vitality had no significant change after 3 months of treatment with cART however, there was a significant increase (p < 0.05) in testosterone from 2.48 to 3.68 ng/ml, but luteinizing hormone decreased significantly (p < 0.05) from 9.6 to 6.5 mIU/ml. In addition, sperm DNA fragmentation increased significantly (p < 0.01). Conversely, viral load, and catalase decreased significantly, but no significant difference in malondialdehyde. This study showed that HIV depleted testosterone and impaired sperm motility which may negatively affect the fertility potential of men living with HIV. It also showed that adherence to cART (a combination of tenofovir, lamivudine, and dolutegravir) reduces the viral load and reverses the deleterious effects of cART albeit, cART appears to be toxic at subcellular spermatogenic levels.

Effects of vancomycin linoleic acid nanoparticles on male reproductive indices of Sprague-Dawley rats.

The management of bacterial infections, especially trains of methicillin-resistant Staphylococcus aureus observe in health care settings, has markedly improved with the introduction of established drugs but using newer nano-based formulations. This study investigates the effects of vancomycin-linoleic acid nanoparticles on testicular tissue in an experimental animal model. Twenty-five adult male Sprague-Dawley rats maintained at the Animal House of the Biomedical Resources Unit were assigned to five groups namely E - solid lipid nanoparticles; F - vancomycin solid lipid nanoparticle; G - linoleic acid nanoparticle; H - vancomycin linoleic acid; and A - control. Perturbations in seminal fluid parameters showed a reduced sperm count in groups F & G which was statistically significant (p < .05) but motility and morphology were not significant when compared to controls (A). Reduced testosterone levels were found in groups E, F and H but were not statistically significant (p > .05). There was also increased luteinizing hormone (LH) and decreased in follicular stimulating hormone (FSH) levels was statistically significant (p < .05). Hypoplasia, tubular atrophy and shrinkage were observed in histologic sections of the treated groups with basement membrane thickening. Vancomycin solid lipid nanoparticle and its constituents SLN and LA disrupted testicular morphometry and the hormonal milieu sufficient to potentially induce altered reproductive function.

Development and evaluation of mucoadhesive bigel containing tenofovir and maraviroc for HIV prophylaxis.

BACKGROUND: Sexual transmission of HIV is the most common means of acquiring the disease. Topical microbicides have been investigated to prevent transmission. This study will use a specific entry inhibitor, maraviroc, and a nucleotide reverse transcriptase inhibitor (NRTI), tenofovir, a dual combination which will provide a synergist effect that can enhance the efficacy of HIV microbicides via a mucoadhesive dual compartment bigel. Bigel formulation via hydrogel organogel linkages were developed and evaluated for their physicochemical characteristics, safety, and anti-HIV efficacy. In vitro diffusion studies were performed with Franz diffusion cells having effective diffusion surface area of 1.76cm2 and receiver chamber volume of 15mL. RESULT: The bigel formulations showed a viscosity ranging from 14179 to 14560 cPs and had a good spreadability and acidic pH in the range of 4.0 ± 0.34 to 5.2 ± 0.18. The bigel formulations showed good anti-HIV activity at a concentration of 0.1 µg/mL. The in vitro release study of maraviroc from the bigel formulations showed a release rate ranging from 2.675 to 3.838 µg/cm2/min½ while the release rate for tenofovir ranged from 3.475 to 3.825 µg/cm2/min½. The bigel formulations were non-toxic to the human vagina as there was < 1 log10 change in Lactobacilli crispatus viability. CONCLUSION: This study successfully developed a dual compartment bigel containing maraviroc and tenofovir. BG C was found to be stable and safe towards vaginal and rectal epithelium, and it actively prevented HIV transmission. This bigel has the potential for long-term pre-exposure prophylaxis prevention of HIV transmission.

Microscopic and biochemical changes on liver and kidney of Wistar rats on combination antiretroviral therapy: the impact of naringenin and quercetin.

Combination antiretroviral therapy (cART), which is a lifelong therapy for people living with human immunodeficiency virus, has been associated with nephrotoxicity and hepatotoxicity leading to its discontinuation. This study aimed at investigating the ameliorative potential of naringenin and quercetin on cART-induced hepatotoxicity and nephrotoxicity. Seventy male Wistar rats (225-260 g) were divided into seven groups as control, cART, naringenin, quercetin, dimethyl sulfoxide (DMSO), naringenin/cART (CN) and quercetin/cART (CQ). cART (24 mg/kg), naringenin (50 mg/kg) and quercetin (50 mg/kg) were dissolved in 1% v/v DMSO and administered orally for 56 days. Combination of cART and bioflavonoids had significant increase in superoxide dismutase (P < 0.05), catalase (P < 0.01), reduced glutathione (P < 0.001) and decreased malondialdehyde (P < 0.001) compared to cART only. Tumor necrosis factor Alpha (TNFα) level increased significantly in cART and CQ (P < 0.01) groups, while others showed no significant changes compared to control. TNFα also significantly decreased in CQ level compared to cART (P < 0.001). In addition, significant increase in creatinine level in cART only indicated progressive renal toxicity. Also, progressive pathological changes including congested blood vessels and hepatocellular necrosis were found in the liver, while the kidney had glomerular atrophy, and tubular distortion in cART-only group. Control, naringenin- and quercetin-treated groups showed normal renal and hepatic cytoarchitecture. These findings elucidate that progressive renal and hepatic toxicity is associated with the continuous use of cART; however, a combination of quercetin and naringenin with cART showed possible potential of ameliorating the damages posed by cART.

Modeling cerebellar limb dysmetria and impaired spatial memory in rats using lamivudine: A preliminary study.

BACKGROUND AND AIM: Neurodegeneration has been associated with the use of combination antiretroviral therapy (cART). This study is aimed at determining if any constituent of cART can induce cerebellar limb dysmetria and spatial memory impairments. MATERIALS AND METHODS: Forty adult male Wistar rats were randomly grouped into four (n = 10): control (distilled water 0.5 mL); Tenofovir (6 mg/kg); Lamivudine (6 mg/kg) and Efavirenz (12 mg/kg). The following neurobehavioral studies were conducted: open field, beam walk, and Morris water maze. Immunohistochemistry of CD 68 and GFAP were used to test for neuroinflammation and neurodegeneration. RESULTS: There was marked increase in pyknotic pyramidal cells of the hippocampus and ghost Purkinje cells in the cerebellum of treatment groups. There was also a significant increase in oxidative stress in lamivudine and efavirenz groups. In addition, Lamivudine caused a significant increase of microglial and astrocytic activity (p < 0.001, 0.05 respectively) compared to control. The open field test showed a significant decrease (p < 0.0001) of the line crossing performance in the efavirenz, lamivudine and tenofovir (with means: 26.4, 4.6, 17.4 respectively) compared to control (50.6). There was also a significant decrease in the grooming (p < 0.05) and rearing (p < 0.01) in lamivudine group. Whereas, walk latency increased in efavirenz (p < 0.01), and lamivudine (p < 0.0001) compared to control. While hind limb slips significantly increased in efavirenz (p < 0.05) and lamivudine (p < 0.0001) compared with control group. Likewise, Lamivudine and Tenofovir exposed groups experienced a significant delay in the time to identify the hidden platform in compared to control (p < 0.05). CONCLUSION: Lamivudine altered efferent stimuli along the cerebellospinal tracts thereby causing motor impairments. The degenerating Purkinje fibers may have induced marked neurodegeneration in the hippocampus resulting in impaired spatial memory.

Combination antiretroviral therapy (cART)-induced hippocampal disorders: Highlights on therapeutic potential of Naringenin and Quercetin.

INTRODUCTION: In spite of the multiple benefits of combination antiretroviral therapy (cART) on HIV positive patients, prolonged usage has been reported to exacerbate oxidative stress, and induce neurological and cognitive dysfunction, thus, the need to search for an adjuvant therapy to ameliorate the oxidative and improve treatment adherence with better virological outcome. This study aimed at determining the potential therapeutic effects of Quercetin and Naringenin on cART-induced cyto-architectural, neuro-behavioral and immunohistochemical changes in the hippocampus of the adult Wister rats. MATERIALS AND METHODS: The animals were grouped as follows: Control, DMSO, 24 mg/kg cART (Tenovovir 300 mg, Lamivudine 300 mg and Efavirenz 600 mg), 50 mg/kg Naringenin, 50 mg/kg Quercetin, cART + Naringenin, cART + Quercetin were administered orally for 8 weeks. At the end of administration, neurobehavioural test was conducted, animals were euthanized and hippocampus was processed for oxidative stress markers, histology, TNF-α, and Monoamine oxidase-B expression. RESULTS: At the end of 8 weeks of administration, 24 mg/kg cART decreased superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and increased Malondialdehyde (MDA). Whereas, 50 mg/kg quercetin, and 50 mg/kg Naringenin decreased the oxidative stress (increased SOD, CAT, GSH, and reduced MDA) induced by cART (reduced SOD, CAT, GSH, and increased MDA). In addition, hematoxylin and eosin stained hippocampus showed that quercetin and naringenin prevented neurodegenerative changes (marked cytoplasmic shrinkage and several pyknotic nuclei in the dentate gyrus and cornus ammonis regions) in cART-treated rats. Furthermore, immunohistochemical studies revealed that quercetin and naringenin attenuates cART-induced upregulation of monoamine oxidase-B (MAO-B) expression. Likewise, from the Morris water maze neurobehavioral studies, naringenin and quercetin also ameliorated cART-induced memory impairments (initial spatial memory, reversal spatial memory and probe tests). CONCLUSION: This study shows that Naringenin and Quercetin have a good potential in reversing cART-induced hippocampal disorders in Wistar rats.

Histological and biochemical effects of Cinnamomum cassia nanoparticles in kidneys of diabetic Sprague-Dawley rats.

This study investigated the antidiabetic activity of Cinnamomum cassia (C. cassia, Cc) silver nanoparticles (CcAgNPS) and effects of C. cassia on the kidneys of rats with induced type 2 diabetes. Twenty-four Sprague-Dawley rats weighing 250 ± 20 g were induced with diabetes by intraperitoneal injection of streptozotocin (STZ, 60 mg/kg). Animals were randomly assigned to one of four groups (n = 6) and treated for eight weeks with normal saline (control, group A), 5 mg/kg of CcAgNPs (group B), 10 mg/kg of CcAgNPs (group C), or 200 mg/kg of Cc (group D). Body weight and fasting blood glucose (FBG) was measured weekly and fortnightly, respectively. At the end of experiments animals were euthanized, blood and kidney tissue samples were collected for biochemistry (oxidative stress markers and renal function parameters) and kidneys were harvested for histology (PAS and H.

Testicular 3beta hydroxysteroid dehydrogenase in naringenin adjuvant under highly active antiretroviral therapy (HAART); preliminary data using Sprague-Dawley rats

HAART has brought relief to many living with HIV/AIDS, decreasing morbidity and mortality rates. In spite of these benefits, the treatment has been associated with reproductive disorders. This study is aimed at investigating the effects of Naringenin (Nar) on the expression of testicular 3ß-Hydroxysteroid dehydrogenase (3ß HSD) in HAART-treated Sprague-Dawley rats. 30 adult male Sprague-Dawley rats were randomly divided into six groups. The rats were fed with 30 mg/kg of HAART (Efavirenz+Embtricitabine+Tenofovir), 40mg/kg and 80 mg/kg of Nar and a combination of both HAART and Nar for a period of 70 days. Thereafter, the animals were euthanized and the testes processed. The results showed a significant decrease (p<0.05) in the expression of 3ß HSD in the HAART group compared to controls. However, the co-treatment of HAART with 40 mg/kg Nar increased significantly (p<0.05) the expression of 3ß HSD, compared to HAART and control. The relative volume fraction also showed significant increase (p<0.05) in germinal epithelium, lumen and Leydig cells of animals treated with 80 mg/kg Nar, and HAART+40 mg/kg Nar compared to control and HAART respectively. In conclusion, HAART is causes a deficiency in testicular 3ß HSD, thereby limiting spermatogenesis. However, co-treatment with 40 mg/kg Naringenin increases testicular 3ß HSD expression and enhances spermatogenesis

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Testicular microanatomical and hormonal alterations following use of antiretroviral therapy in Sprague Dawley rats: Role of Naringenin.

Human immunodeficiency virus-infected man may require assisted reproductive technology not just for safer conception but also due to subfertility. The study investigated the effect of antiretroviral drugs on the fertility potentials of males and the possible protective role of Naringenin, using Sprague Dawley rats. Thirty adult male Sprague Dawley rats were grouped into-A: Distilled water; B: Highly Active Antiretroviral Therapy (HAART); C: Naringenin 40 mg/kg; D: Naringenin 80 mg/kg, E: HAART + Naringenin 40 mg/kg; F: HAART + Naringenin 80 mg/kg. The rats were euthanised after 10 weeks. Results showed a significant decrease in sperm count in group B when compared to the control and other groups. Spermatozoa with normal morphology also reduced significantly in the B group and progressive sperm motility reduced when compared to the control, D and the F group. The serum testosterone was not significantly different between groups A and B, however the groups C and D displayed significant increase when compared to groups A and B. The serum luteinising hormone was significantly higher in group B when compared to groups A, E and F. Our data suggest that Naringenin improves the male reproductive anatomy and function, therefore, it promises to be a beneficial adjuvant for mitigating HAART testicular and reproductive perturbations.

A comparison of the anti-diabetic potential of d-ribose-l-cysteine with insulin, and oral hypoglycaemic agents on pregnant rats.

Over 18% of pregnant women are affected by diabetes mellitus (DM) and Insulin has been the commonest drug used in its treatment. There are reports of noncompliance to insulin due to trypanophobia, with suggestions for the use of oral hypoglycaemic agents (OHAs). However, the opposing views about the benefits and risk of oral hypoglycaemic agents (OHAs) warrant a continuous search for an alternative regimen. Therefore, this study is aimed at comparing the antidiabetic effects of d-ribose-l-cysteine (riboceine) with vildagliptin, glibenclamide, metformin, glipizide and insulin in diabetes in pregnancy. Forty (40) female Sprague-Dawley (SD) rats were mated with twenty (20) male SD rats. Diabetes was induced by streptozotocin and the female SD rats were divided into 8 groups of five (5) rats each. The animals were administered either of the OHAs vildagliptin, glibenclamide, metformin, glipizide and riboceine for a period of 19 gestational days. The results showed that streptozotocin (STZ) significantly (p < 0.05) decreased the weights of the animals, increased malondialdehyde, blood glucose levels and altered reproductive hormones. These effects of STZ were better ameliorated in animals that received insulin and riboceine compared to the other OHAs. While progesterone levels were significantly (p < 0.05) higher in animals that received riboceine compared to insulin. Glibenclamide increased (p < 0.05) foetal weights compared to non-diabetic animals. In conclusion, glibenclamide may be a threat to mother`s life in the management of diabetes in pregnancy however, riboceine as well as vildagliptin, metformin and glipizide are effective oral hypoglycaemic agents which could serve as a potent adjuvant comparable to insulin in the management of diabetes during gestation.

Investigating Organ Toxicity Profile of Tenofovir and Tenofovir Nanoparticle on the Liver and Kidney: Experimental Animal Study.

Tenofovir nanoparticles are novel therapeutic intervention in human immunodeficiency virus (HIV) infection reaching the virus in their sanctuary sites. However, there has been no systemic toxicity testing of this formulation despite global concerns on the safety of nano drugs. Therefore, this study was designed to investigate the toxicity of Tenofovir nanoparticle (NTDF) on the liver and kidney using an animal model. Fifteen adult male Sprague-Dawley (SD) rats maintained at the animal house of the biomedical resources unit of the University of KwaZulu-Natal were weighed and divided into three groups. Control animals (A) were administered with normal saline (NS). The therapeutic doses of Tenofovir (TDF) and nanoparticles of Tenofovir (NTDF) were administered to group B and C and observed for signs of stress for four weeks after which animals were weighed and sacrificed. Liver and kidney were removed and fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT) and liver function test (LFT). Cellular measurements and capturing were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, p values < 0.05 were significant. We observed no signs of behavioural toxicity and no mortality during this study, however, in the kidneys, we reported mild morphological perturbations widening of Bowman's space, and vacuolations in glomerulus and tubules of TDF and NTDF animals. Also, there was a significant elevation of glycogen deposition in NTDF and TDF animals when compared with control. In the liver, there were mild histological changes with widening of sinusoidal spaces, vacuolations in hepatocytes and elevation of glycogen deposition in TDF and NTDF administered animals. In addition to this, there were no significant differences in stereological measurements and cell count, LFT, RFT, weight changes and organo-somatic index between treatment groups and control. In conclusion, NTDF and TDF in therapeutic doses can lead to mild hepatic and renal histological damage. Further studies are needed to understand the precise genetic mechanism.

Effect of long-term administration of Cinnamomum cassia silver nanoparticles on organs (kidneys and liver) of Sprague-Dawley rats.

This study investigated the toxic effects of silver on the kidneys and livers of Sprague-Dawley rats after administering multiple doses of silver nanoparticles synthesized using extracts of Cinnamomum cassia (CcAgNPs). Twenty-four Sprague-Dawley rats (250 ± 20 g) were randomly assigned to four groups (A-D) of six animals per group and treated for 8 weeks. Group A was administered 200 mg/kg of Cinnamon Cassia extract (Cc), group B 5 mg/kg of CcAgNPs, group C 10 mg/kg of CcAgNPs, and group D normal saline. Body weight was measured weekly and fasting blood glucose was measured fortnightly. At the end of the experiment, animals were euthanized and organs (livers and kidneys) were fixed in neutral buffered formalin and processed for light microscopy (H&E). Body weight differences were significantly higher (P < 0.05) in the low-dose Cc group and the kidney to body weight ratio was not significant. Renal function analysis of proteins and ketones showed a significant increase in CcAgNP-treated rats (P < 0.05). Kidney and liver histology showed distortions in hepatocytes and sinusoidal linings with infiltrations especially in the higher dose groups. Kidney histology mirrored degenerative changes in glomerular and Bowman's capsules with bfirillary mesangial interstitium. CcAgNPs impairs renal and hepatic morphology and function after a long period of administration.

Post-treatment with Telfairia occidentalis seed oil attenuates alcohol-induced testicular damage in Sprague-Dawley rats.

BACKGROUND: Long term alcohol use has been implicated in men with sexual disorders including suppression of testosterone levels as well as testicular morphological changes. OBJECTIVE: This research investigated the ability of Telfairia occidentalis (T.O.) to attenuate the damaging effects of alcohol on the testicular parameters. MATERIALS AND METHODS: Thirty male Sprague-Dawley rats, 170-190 grams were divided into 6 groups, A to F and treated with distilled water (DW) for the period of 8 weeks (positive control group A), ethanol for 2 weeks followed with DW for 6 weeks (group B) (negative control), ethanol alone for 2 weeks (group C) while others received ethanol for 2 weeks, followed with 200 (group D), 400 (group E) and 600 mg/kg (group F) of T.O. for 6 weeks. RESULTS: Testicular histological sections showed that ethanol produced marked loss of testicular germ cells after two weeks of administration. T.O (200 mg/kg body weight) was not able to attenuate this microanatomical distortion when compared with control groups, but at 400 mg/kg body weight, T.O reversed the ethanol`s effects with resultant significant increase in sperm count and motility (p<0.05), serum testosterone levels (p<0.05), and testicular weight (p<0.05). However, at 600 mg/kg dosage, there was marked depletion of testicular germ cells with atrophied seminiferous tubules and a decrease in semen parameters and testicular weight. CONCLUSION: Our result suggests that T.O promotes the regeneration of testicular germ cells and improves semen quality at a certain critical dose. Hence, T.O has a potential of reversing ethanol induced testicular damage.