Browsing by Author "Omolaoye, Temidayo S."

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Descriptive histomorphological evaluation of the testis and caudal epididymis following treatment with rooibos (Aspalathus linearis), honeybush (Cyclopia intermedia) and sutherlandia (Lessertia frutescens) in healthy and streptozotocininduced diabetic rats
(2021) Omolaoye, Temidayo S.; Plessis, Stefan S du
Objective: To evaluate the testis and the cauda epididymis after treating both healthy and diabetic rats with rooibos (Aspalathus linearis), honeybush (Cyclopia intermedia), and sutherlandia (Lessertia frutescens), respectively. Methods: Ninety male Wistar rats were randomly divided into nine groups (n=10 per group). Fifty rats were randomized to receive tap water, 0.1 M citrate buffer, 2.0% fermented rooibos, 4.0% fermented honeybush, or 0.2% unfermented sutherlandia. Diabetes was induced via a single intraperitoneal injection of streptozotocin (STZ) at 45 mg/kg in 40 rats. The diabetic rats were randomized to receive tap water, 2.0% fermented rooibos, 4.0% fermented honeybush, or 0.2% unfermented sutherlandia. Rats were sacrificed after seven weeks of diabetic induction. Blood was collected for hormonal assay, while the testes and caudal epididymis were retrieved for histomorphological evaluations. Results: Diabetic rats treated with 2.0% fermented rooibos exhibited a significant increase in fasting plasma glucose (FPG) versus the vehicle group (P=0.002), and a 3.6% decrease compared to the diabetic control group (P>0.05). Diabetic rats treated with honeybush or sutherlandia showed 23.6% and 15.4% decrease in FPG when compared to the diabetic control group, respectively (both P>0.05). The diabetic control rats had a significant decrease in the percentage of histologically normal seminiferous tubules compared to the control group (P=0.049). There was 21.0%, 14.0%, and 5.4% rise in the percentage of normal seminiferous tubules in diabetic rats receiving rooibos, honeybush or sutherlandia, respectively, compared to the diabetic control group. The infusion control groups (rooibos, honeybush and sutherlandia) showed normal seminiferous tubules, presence of spermatozoa in the epididymal lumen, and had normal overall architecture. Both testicular and epididymal morphology were altered in the diabetic control group, but these disruptions were mildly ameliorated by rooibos, honeybush, and sutherlandia. Conclusions: The detrimental effects of diabetes on the histomorphological architecture of the testis and epididymis are mildly ameliorated by the infusions (2.0% fermented rooibos, 4.0% fermented honeybush, and 0.2% unfermented sutherlandia).
The effect of Aspalathin linearis, Cyclopia intermedia and Sutherlandia frutescene on sperm functional parameters of healthy male wistar rats
(2023) Omolaoye, Temidayo S.; Plessis, Stefan Du
Introduction: Rooibos (Aspalathin linearis), honeybush (Cyclopia intermedia), and sutherlandia (Sutherlandia frutescene) are three Southern Africa indigenous plants, of which the extracts have become house-hold items and are consumed on a large scale. Although, they are known for their antioxidant properties, studies have highlighted danger in the excessive intake. Therefore, the current study investigated whether treatment with rooibos, honeybush, and sutherlandia will impact sperm functional parameters positively or otherwise, in healthy rats. Methods: Fourteen-week-old pathogen-free adult male Wistar rats (250–300 g) were randomly divided into four groups of ten, including a control, rooibos (RF), honeybush (HB) and a sutherlandia (SL) group. After 7 weeks of treatment, animals were sacrificed. Spermatozoa were retrieved from the cauda epididymis for motility, morphology and concentration analysis and the testis was used for all biochemical assays. Results: The infusion treated animals (RF, HB, and SL) presented with a non-significant decrease of −14.3%, −18.2%, −17.2% and −24.8%, −20.7%, −27.3% in total motility and progressive motility when compared to the control group, respectively. There was a significant increase in number of spermatozoa with slow speed (p = 0.03), especially in SL treated group compared to the control (p = 0.03). Additionally, there was an increase of 28.8%, 31.7%, 23% in superoxide dismutase (SOD) activity of RF, HB and SL compared to control, respectively. This was accompanied with a percentage decrease of −21.1%, −23.7%, 45.9% in malondialdehyde (MDA) levels compared to the control group. Conclusion: In summary, animals treated with the respective infusions presented with a percentage increase in SOD activity but have reduced sperm motility and decreased normal morphology. Paradoxically, they presented with increased sperm concentration. Hence, it is presumed that rooibos, honeybush and sutherlandia may enhance sperm quantity (concentration) but may impair sperm quality (motility morphology) when consumed by healthy animals.
The Effect of Statins on Male Reproductive Parameters: A Mechanism Involving Dysregulation of Gonadal Hormone Receptors and TRPV1
(2023) Omolaoye, Temidayo S.; Cyril, Asha Caroline; Radhakrishnan, Rajan; Rawat, Surendra Singh; Karuvantevida, Noushad; Du Plessis, Stefan
Abstract: Statins have been shown to cause diverse male reproductive function impairment, and in some cases, orchialgia. Therefore, the current study investigated the possible mechanisms through which statins may alter male reproductive parameters. Thirty adult male Wistar rats (200–250 g) were divided into three groups. The animals were orally administered rosuvastatin (50 mg/kg), simvastatin (50 mg/kg), or 0.5% carboxy methyl cellulose (control), for a 30-day period. Spermatozoa were retrieved from the caudal epididymis for sperm analysis. The testis was used for all biochemical assays and immunofluorescent localization of biomarkers of interest. Rosuvastatin-treated animals presented with a significant decrease in sperm concentration when compared to both the control and simvastatin groups (p < 0.005). While no significant difference was observed between the simvastatin and the control group. The Sertoli cells, Leydig cells and whole testicular tissue homogenate expressed transcripts of solute carrier organic anion transporters (SLCO1B1 and SLCO1B3). There was a significant decrease in the testicular protein expression of the luteinizing hormone receptor, follicle stimulating hormone receptor, and transient receptor potential vanilloid 1 in the rosuvastatin and simvastatin-treated animals compared to the control. The expression of SLCO1B1, SLCO1B2, and SLCO1B3 in the different spermatogenic cells portray that un-bio transformed statin can be transported into the testicular microenvironment, which can subsequently alter the regulation of the gonadal hormone receptors, dysregulate pain-inflammatory biomarkers, and consequently impair sperm concentration.
Mechanisms of SARS-CoV-2 and Male Infertility: Could Connexin and Pannexin Play a Role?
(2022) Omolaoye, Temidayo S.; Jalaleddine, Nour; Du Plessis, Stefan
Abstract: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on male infertility has lately received significant attention. SARS-CoV-2, the virus that causes coronavirus disease (COVID-19) in humans, has been shown to impose adverse effects on both the structural components and function of the testis, which potentially impact spermatogenesis. These adverse effects are partially explained by fever, systemic inflammation, oxidative stress, and an increased immune response leading to impaired blood-testis barrier. It has been well established that efficient cellular communication via gap junctions or functional channels is required for tissue homeostasis. Connexins and pannexins are two protein families that mediate autocrine and paracrine signaling between the cells and the extracellular environment. These channel-forming proteins have been shown to play a role in coordinating cellular communication in the testis and epididymis. Despite their role in maintaining a proper male reproductive milieu, their function is disrupted under pathological conditions. The involvement of these channels has been well documented in several physiological and pathological conditions and their designated function in infectious diseases. However, their role in COVID-19 and their meaningful contribution to male infertility remains to be elucidated. Therefore, this review highlights the multivariate pathophysiological mechanisms of SARS-CoV-2 involvement in male reproduction. It also aims to shed light on the role of connexin and pannexin channels in disease progression, emphasizing their unexplored role and regulation of SARS-CoV-2 pathophysiology. Finally, we hypothesize the possible involvement of connexins and pannexins in SARS-CoV-2 inducing male infertility to assist future research ideas targeting therapeutic approaches.
The mutagenic effect of tobacco smoke on male fertility
(2021) Omolaoye, Temidayo S.; Boillat, Thomas; Loney, Tom; Plessis, Stefan S du
Abstract: Despite the association between tobacco use and the harmful effects on general health as well as male fertility parameters, smoking remains globally prevalent. The main content of tobacco smoke is nicotine and its metabolite cotinine. These compounds can pass the blood-testis barrier, which subsequently causes harm of diverse degree to the germ cells. Although controversial, smoking has been shown to cause not only a decrease in spermmotility, spermconcentration, and an increase in abnormal sperm morphology, but also genetic and epigenetic aberrations in spermatozoa. Both animal and human studies have highlighted the occurrence of sperm DNA-strand breaks (fragmentation), genome instability, genetic mutations, and the presence of aneuploids in the germline of animals and men exposed to tobacco smoke. The question to be asked at this point is, if smoking has the potential to cause all these genetic aberrations, what is the extent of damage? Hence, this review aimed to provide evidence that smoking has a mutagenic effect on sperm and how this subsequently affects male fertility. Additionally, the role of tobacco smoke as an aneugen will be explored.We furthermore aim to incorporate the epidemiological aspects of the aforementioned and provide a holistic approach to the topic.
Omics and Male Infertility: Highlighting the Application of Transcriptomic Data
(2022) Omolaoye, Temidayo S.; Kandasamy, Richard K; Hachim, Mahmood Yaseen; Du Plessis, Stefan; Omolaoye, Victor A
Abstract: Male infertility is a multifaceted disorder affecting approximately 50% of male partners in infertile couples. Over the years, male infertility has been diagnosed mainly through semen analysis, hormone evaluations, medical records and physical examinations, which of course are fundamental, but yet inefficient, because 30% of male infertility cases remain idiopathic. This dilemmatic status of the unknown needs to be addressed with more sophisticated and result-driven technologies and/or techniques. Genetic alterations have been linked with male infertility, thereby unveiling the practicality of investigating this disorder from the “omics” perspective. Omics aims at analyzing the structure and functions of a whole constituent of a given biological function at different levels, including the molecular gene level (genomics), transcript level (transcriptomics), protein level (proteomics) and metabolites level (metabolomics). In the current study, an overview of the four branches of omics and their roles in male infertility are briefly discussed; the potential usefulness of assessing transcriptomic data to understand this pathology is also elucidated. After assessing the publicly obtainable transcriptomic data for datasets on male infertility, a total of 1385 datasets were retrieved, of which 10 datasets met the inclusion criteria and were used for further analysis. These datasets were classified into groups according to the disease or cause of male infertility. The groups include non-obstructive azoospermia (NOA), obstructive azoospermia (OA), non-obstructive and obstructive azoospermia (NOA and OA), spermatogenic dysfunction, sperm dysfunction, and Y chromosome microdeletion. Findings revealed that 8 genes (LDHC, PDHA2, TNP1, TNP2, ODF1, ODF2, SPINK2, PCDHB3) were commonly differentially expressed between all disease groups. Likewise, 56 genes were common between NOA versus NOA and OA (ADAD1, BANF2, BCL2L14, C12orf50, C20orf173, C22orf23, C6orf99, C9orf131, C9orf24, CABS1, CAPZA3, CCDC187, CCDC54, CDKN3, CEP170, CFAP206, CRISP2, CT83, CXorf65, FAM209A, FAM71F1, FAM81B, GALNTL5, GTSF1, H1FNT, HEMGN, HMGB4, KIF2B, LDHC, LOC441601, LYZL2, ODF1, ODF2, PCDHB3, PDHA2, PGK2, PIH1D2, PLCZ1, PROCA1, RIMBP3, ROPN1L, SHCBP1L, SMCP, SPATA16, SPATA19, SPINK2, TEX33, TKTL2, TMCO2, TMCO5A, TNP1, TNP2, TSPAN16, TSSK1B, TTLL2, UBQLN3). These genes, particularly the above-mentioned 8 genes, are involved in diverse biological processes such as germ cell development, spermatid development, spermatid differentiation, regulation of proteolysis, spermatogenesis and metabolic processes. Owing to the stage-specific expression of these genes, any mal-expression can ultimately lead to male infertility. Therefore, currently available data on all branches of omics relating to male fertility can be used to identify biomarkers for diagnosing male infertility, which can potentially help in unravelling some idiopathic cases.
Oxidative Stress and Male Infertility: Evidence From a Research Perspective
(2022) Omolaoye, Temidayo S.; Plessis, Stefan S. du
Abstract: Male fertility potential can be influenced by a variety of conditions that frequently coincide. Spermatozoa are particularly susceptible to oxidative damage due to their limited antioxidant capacity and cell membrane rich in polyunsaturated fatty acids (PUFAs). The role of oxidative stress (OS) in the etiology of male infertility has been the primary focus of our Stellenbosch University Reproductive Research Group (SURRG) over the last 10 years. This review aims to provide a novel insight into the impact of OS on spermatozoa and male reproductive function by reviewing the OS-related findings from a wide variety of studies conducted in our laboratory, along with those emerging from other investigators. We will provide a concise overview of the production of reactive oxygen species (ROS) and the development of OS in the male reproductive tract along with the physiological and pathological effects thereof on male reproductive functions. Recent advances in methods and techniques used for the assessment of OS will also be highlighted. We will furthermore consider the current evidence regarding the association between OS and ejaculatory abstinence period, as well as the potential mechanisms involved in the pathophysiology of various systemic diseases such as obesity, insulin resistance, hypertension, and certain mental health disorders which have been shown to cause OS induced male infertility. Finally, special emphasis will be placed on the potential for transferring and incorporating research findings emanating from different experimental studies into clinical practice.
Statins and Male Fertility: Is There a Cause for Concern?
(2022) Omolaoye, Temidayo S.; Mubarak, Maitha; Cyril, Asha Caroline; Duvuru, Ruthwik; Radhakrishnan, Rajan; Du Plessis, Stefan
Abstract: The well-known 3-hydroxyl 3-methyl glutaryl-Coenzyme A reductase inhibitors, called statins, have been the main medication used in the treatment of hypercholesterolemia and some cases of cardiovascular diseases. The effectiveness of this drug in controlling cholesterol production is impeccable, however, patients often complain of a variety of side effects, such as myalgia, muscle atrophy, and in some cases, rhabdomyolysis. Not only has the use of statins caused the aforementioned side effects, but they are also shown to cause testicular discomfort, erectile dysfunction, altered semen parameters, and modified steroid hormone production. These reported adverse effects on male fertility are not generally agreed upon, as some have shown the use to be beneficial. Hence, this makes the aftermath effect of statin use on male fertility debatable and controversial. The negative effects have been associated with imbalanced or reduced steroid hormones, which are necessary for proper spermatogenesis and other sexual functions. Meanwhile, the beneficial effects are related to statin’s anti-inflammatory and cardioprotective properties. These contradictory findings are in part due to the different age of users, concentrations of statins, the type and duration of treatment, and the underlying disease and/or comorbidities. Therefore, the current study aims to analyze the literature and gather evidence as to the effects of statin on male sexual health and reproductive parameters, and subsequently give recommendations for the direction of future studies.
Using publicly available transcriptomic data to identify mechanistic and diagnostic biomarkers in azoospermia and overall male infertility
(2022) Omolaoye, Temidayo S.; Hachim, Mahmood Yaseen; Du Plessis, Stefan
Abstract Azoospermia, which is the absence of spermatozoa in an ejaculate occurring due to defects in sperm production, or the obstruction of the reproductive tract, afects about 1% of all men and is prevalent in up to 10–15% of infertile males. Conventional semen analysis remains the gold standard for diagnosing and treating male infertility; however, advances in molecular biology and bioinformatics now highlight the insufciency thereof. Hence, the need to widen the scope of investigating the aetiology of male infertility stands pertinent. The current study aimed to identify common diferentially expressed genes (DEGs) that might serve as potential biomarkers for non-obstructive azoospermia (NOA) and overall male infertility. DEGs across diferent datasets of transcriptomic profling of testis from human patients with diferent causes of infertility/ impaired spermatogenesis and/or azoospermia were explored using the gene expression omnibus (GEO) database. Following the search using the GEOquery, 30 datasets were available, with 5 meeting the inclusion criteria. The DEGs for datasets were identifed using limma R packages through the GEO2R tool. The annotated genes of the probes in each dataset were intersected with DEGs from all other datasets. Enriched Ontology Clustering for the identifed genes was performed using Metascape to explore the possible connection or interaction between the genes. Twenty-fve DEGs were shared between most of the datasets, which might indicate their role in the pathogenesis of male infertility. Of the 25 DEGs, eight genes (THEG, SPATA20, ROPN1L, GSTF1, TSSK1B, CABS1, ADAD1, RIMBP3) are either involved in the overall spermatogenic processes or at specifc phases of spermatogenesis. We hypothesize that alteration in the expression of these genes leads to impaired spermatogenesis and, ultimately, male infertility. Thus, these genes can be used as potential biomarkers for the early detection of NOA.