Onyemaechi Okpara Azu

Testicular histomorphologic and stereological alterations following short-term treatment with highly active antiretroviral drugs (HAART) in an experimental animal model

The increased accessibility of antiretroviral therapy continues to positively drive the reduction in viral load and survival of patients despite the attendant reproductive toxicities. We propose that testicular damage caused by highly active antiretroviral therapy (HAART) can be attenuated by antioxidant treatment by investigating the testicular histomorphologic and stereological effects of antiretroviral drugs and its interaction with antioxidants using an experimental animal model. Sprague–Dawley rats were divided into seven groups of six rats per group (A, B… G) using simple random sampling and treated orally with 0.9% normal saline as placebo, a HAART cocktail of stavudine, lamivudine and nevirapine using the adjusted human therapeutic doses of 200, 600 and 350–400 mg/day, respectively, and antioxidants ascorbic acid (vitamin C) and I.M α‐tocopherol (vitamin E). Animals were killed after 4 weeks and testicular tissue harvested and processed for light microscopy and stereological evaluations. The results were interpreted by a Veterinary pathologist blinded to the study. No animal died during the experimental period. The histopathological assessment of the testis of animals treated with placebo, ascorbic acid alone and α‐tocopherol alone as well as vitamin E + HAART displayed normal testicular microanatomy. Groups treated with HAART alone, HAART + vitamin C + vitamin E and vitamins C + HAART showed extensive seminiferous tubular atrophy, necrosis and hypocellularity in the histoarchitectural patterns. While testicular cross‐sectional area of seminiferous tubules remained unaffected by HAART, epithelial heights significantly decreased (p < 0.05) when compared with controls. There was marked (p < 0.05) increased in testicular‐body weight ratio in HAART group. The results show that vitamin E could be useful in protecting testicular tissue from toxicities of HAART regimes as these results mirrors stereological data for the groups. HAART presents with deleterious histopathological changes in the testes causing tubular atrophy with altered morphometric indices. Supplementation with vitamin E appears to be a better adjuvant antioxidant that ameliorates these deleterious effects.

Coconut Oil Extract Mitigates Testicular Injury Following Adjuvant Treatment with Antiretroviral Drugs

Increased access to highly active antiretroviral therapy (HAART) has made the management of drug toxicities an increasingly crucial component of HIV. This study investigated the effects of adjuvant use of coconut oil and HAART on testicular morphology and seminal parameters in Sprague- Dawley rats. Twelve adult male Sprague-Dawley rats, weighing 153~169 g were distributed into four groups (A–D) and treated as follows: A served as control (distilled water); B (HAART cocktail- Zidovudine, Lamivudine and Nevirapine); C (HAART + Virgin coconut oil 10 mL/kg) and D (Virgin coconut oil 10 mL/kg). After 56 days of treatment, animals were killed and laparotomy to exercise the epididymis for seminal fluid analyses done whilst testicular tissues were processed for histomorphometric studies. Result showed a significant decline in sperm motility (P < 0.05) and count (P < 0.0001) in HAART-treated animals while there was insignificant changes in other parameters in groups C and D except count that was reduced (P < 0.0001) when compared with controls. Histomorphological studies showed HAART caused disorders in seminiferous tubular architecture with significant (P < 0.01) decline in epithelial height closely mirrored by extensive reticulin framework and positive PAS cells. Adjuvant Virgin coconut oil + HAART resulted in significant decrease in seminiferous tubular diameter (P < 0.05), but other morphometric and histological parameters were similar to control or Virgin coconut oil alone (which showed normal histoarchitecture levels). While derangements in testicular and seminal fluid parameters occurred following HAART, adjuvant treatment with Virgin coconut oil restored the distortions emanating thereof.

Highly Active Antiretroviral Therapy (HAART) and Testicular Morphology: Current Status and a Case for a Stereologic Approach

As antiretroviral therapy becomes increasingly accessible, the associated improvements in the health, quality of life, and survival of patients are anticipated to influence the fertility determinants of patients, specifically young males, within the reproductive axis. Therefore, the understanding of testicular histology in patients with HIV/AIDS undergoing therapeutic management is essential, because the sexual route is one of the main means of transmission of HIV, which is localized primarily in the germ cells of the testes. It is also important to determine whether any changes have occurred in the testicular histologic patterns in the course of the HIV/AIDS therapy. This review highlights the views of experts that current therapy and prolongation of survival in HIV/AIDS patients are associated with a shift in the histologic findings of testes toward a more pronounced loss of germ cells. There have been attempts to use stereologic size and number estimators to quantify the volume or number of biologically significant reference spaces and objects from their appearance on two-dimensional sections without introducing bias from inappropriate assumptions, models, or correction formulas. Therefore, morphologic changes related to altered distribution of highly active retroviral therapy within the testis and the consequent endocrine perturbations characteristic of a potential complication of antiretroviral treatment regimens can be analyzed in stereologic dimensions.

Effect of co-administration of Hypoxis hemerocallidea extract and antiretroviral therapy (HAART) on the histomorphology and seminal parameters in Sprague Dawley rats.

Although the successful introduction and rollout of antiretroviral therapy has impacted positively on morbidity and mortality of HIV‐positive patients, its interaction with plant‐based adjuvants remain sparsely investigated. We report the interaction and effects of adjuvant treatment with highly active antiretroviral therapy (HAART) and Hypoxis hemeocallidea (HH) extracts on testicular structure of rats. A total of 63 pathogen‐free adult male Sprague Dawley rats were divided into nine groups and treated according to protocols. HAART cocktail predisposed to significant negative testicular parameters of sperm count, motility and seminiferous tubular epithelial height (quantitatively) (p < .03) and also altered the histomorphology of tubules with diffuse hypoplasia in seminiferous tubules. The higher dose of HH showed a better ability to mitigate the altered parameters and compares favourably with vitamin C in this protocol. While HH did not show any deleterious impact on morphometric data, its role as adjuvant did not significantly reduce the negative impact of HAART on morphometric indices especially with the lower dosage. Further investigations are warranted on the interactions between HAART and Hypoxis.

The Male genital tract in the era of Highly Active Antiretroviral Therapy (HAART): implication for antioxidant therapy.

With nearly two decades following the introduction of Highly Active Antiretroviral Therapy (HAART) in the management of HIV/AIDS, tremendous success has been recorded in the control of HIV replication and overall wellbeing and longevity of afflicted patients. But this success has not been complete as HAART strategy still suffers from a myriad of issues, chiefly deleterious side effects owing to oxidative stress-induced cellular injuries. Pointless to say that this has impeded progress made so far and has left researchers in the continued search for options. With changing trends in fertility concerns of many patients infected with HIV, a gradual but persistent trust towards procreative tendencies of these patients who are still within the reproductive age axis becomes a compelling issue for experts. Numerous research points to the beneficial effects of antioxidant augmentation in HAART especially relevant in the midst of escalated cost of antiretroviral drugs in resource-deprived settings. A continued attempt to elucidate pathophysiological mechanisms involved in HAART-associated oxidative stress-mediated reproductive injuries remains critically important to improving the treatment strategies for this epidemic condition. Therefore, an overview of our current knowledge on HAART induced changes via oxidant-antioxidant pathway becomes pertinent as we unravel the body of knowledge that may be necessary to guide future directions particularly in reproduction

Preliminary study on the antioxidant effect of Kigelia africana fruit extract (Bignoniacieae) in male Sprague-Dawley rats.

Testicular germ cells as well as epididymal maturing spermatozoa are endowed with enzymatic and non-enzymatic scavenger systems to protect lipid peroxidation damage. A number of pathologies and systemic challenges can lead to an antioxidant/pro-oxidant disequilibrium. With increasing interest in herbal therapies for management of some fertility-related and inflammatory conditions, we investigated the antioxidant effect of Kigelia africana fruit extract (KAFE) on normal rats. KAFE showed a non-dose dependent elevation in testicular catalase (p < 0.05), significant decline in malondialdehyde (p < 0.001) and an up-regulation of glutathione (p < 0.001) levels. Seminal parameters were also enhanced by KAFE with the lower dose producing better effects. Male infertility is frequently accompanied by increased testicular or seminal fluid oxidative stress. This result provides further scientific basis for the use of KAFE in the treatment of male infertility.

Testicular morphology in spontaneously hypertensive rat model: oxidant status and stereological implications.

Studies by researchers suggest that reductions in blood flow to the testis could play an important role in the pathogenesis of male infertility. As this oxygen‐dependent organ functions in a state of near anoxia, such a decrease in blood flow may very likely have profound effects on the tissue morphology that ultimately would predispose to various forms of hypo‐spermatogenesis with consequent compromise in reproductive capability. With varying opinions expressed by experts as to the actual culprit or potential pathway and/or effects of pathophysiology of testicular haemodynamics, it still remains debatable whether the observed degenerative changes in testicular tissue are the result of major or minor reductions in flow or the consequence of other vascular pathologies or even extraneous factors. Again, increasing age and male gender have been identified as the single independent risk factors for the occurrence of cardiovascular pathologies with sexual dimorphism highly debated. The investigation of these factors occurring under hypertensive states using the spontaneously hypertensive rat (SHR) as an experimental model has attracted substantial attention in recent past. This review examines the relationships and potential morphologic changes in the testicular tissue under conditions of perturbations in blood flow as seen in the SHR with a view to the proper understanding of the role(s) of various factors that contributes to male subfertility. A suggestion to the use of stereological methods for quantitating various measurements in a highly active and dynamic structure like the testis with its arterial system has been added as this may facilitate a better understanding of the mechanisms implicated under hypertensive conditions.

Naringenin attenuates highly active antiretroviral therapy-induced sperm DNA fragmentations and testicular toxicity in Sprague-Dawley rats

Highly active antiretroviral therapy has evolved over the years, leading to a boost in the quality of life in people living with HIV and AIDS. However, growing evidence has shown that highly active antiretroviral therapy has deleterious effects on the testes and the overall reproductive capacity. Therefore, this study is to determine the adjuvant potential of Naringenin on highly active antiretroviral therapy‐induced perturbations in fertility of male Sprague‐Dawley rats. Thirty adult male Sprague‐Dawley rats were divided into six groups viz – Control; H: 30 mg/kg of highly active antiretroviral therapy (EFV, 600 mg + FTC, 200 mg + TDF, 300 mg); N40: Naringenin, 40 mg/kg; N80: Naringenin, 80 mg/kg; HN40: highly active antiretroviral therapy + Naringenin, 40 mg/kg; HN80: highly active antiretroviral therapy + Naringenin, 80 mg/kg. The rats were euthanized after 4 weeks. Results showed that there was a significant decrease in sperm count (p < 0.001), spermatozoa with normal morphology (p < 0.001) and progressive sperm motility (p < 0.05) of H compared to the control and the HN groups. Likewise, fragmentations increased (p < 0.05) in tail lengths of sperm DNA in H compared to control. HN40 and HN80 decreased tail lengths compared to H (p < 0.001). There was also a decrease in %tail DNA and tail moment in HN40 (p < 0.001) compared to H. Luteinizing hormone significantly increased (p < 0.05) in HN40, HN80, and N40 (p < 0.001) but decreased in H (p < 0.05) compared to control. The diameter of the seminiferous tubules also decreased (p < 0.05) in H compared to control, N80, and HN40. Likewise, the area of the seminiferous tubules in group H decreased (p < 0.05) compared to N80 and HN80. The seminiferous tubules epithelium increased (p < 0.05) in N40 and HN40 compared to H. This study establishes that highly active antiretroviral therapy has deleterious effects on the testicular microanatomy, sperm parameters, and sperm DNA of Sprague‐Dawley rats, which may impair fertility but Naringenin is a potential complimentary adjuvant.

Red Palm Oil Attenuates Lead Acetate Induced Testicular Damage in Adult Male Sprague-Dawley Rats

To study the protective effect of Red Palm Oil (RPO) on testicular damage induced by administration of lead acetate on male Sprague-Dawley rats, 28 rats divided into four groups of 7 animals each were used. They were administered orally with RPO (1 mL and 2 mL) and lead acetate (i.p.) 6 mg/kg body weight/day, respectively. Treatment was conducted for 8 weeks, and 24 hrs after the last treatment the rats were sacrificed using cervical dislocation. Sperms collected from epididymis were used for seminal fluid analyses; while the testes sample was used for ROS and oxidative enzyme activities assessment. Statistical analysis was carried out using GraphPad Prism 5.02 statistical analysis package. Administration of lead acetate increased generation of reactive oxygen species (ROS) significantly (p < 0.05) as evidenced by the elevated value of H2O2 and LPO and decreased GSH level. Also there was reduced epididymal sperm count, poor grade of sperm motility, and lower percentage of normal sperm morphology significantly. Coadministration with RPO, however, has a protective effect against lead toxicity by decreasing H2O2 production, increased GSH level, and increased sperm qualities especially. This shows that RPO has a potential to attenuate the toxic effect of lead on testicular cells preventing possible resultant male infertility.

Ectopic pregnancy: A Nigerian urban experience

Ectopic pregnancy is defined as a pregnancy in which the implantation of the embryo occurs outside the uterine cavity, most frequently in one of the two fallopian tubes or, more rarely, in the abdominal cavity [1]. During the fi rst three months of pregnancy, ectopic pregnancy is the leading cause of maternal morbidity and mortality [2,3] in industrialized countries, and possibly the second most frequent cause in developing countries (after abortion complications) [1]. It is a common obstetric problem the world over. Though the global incidence has been rising during the last three decades [3,4], the incidence of the condition varies from country to country depending on the risk factors predominant in the geographical region. In most of Europe and North America, the incidence of ectopic pregnancy has tripled over the last 30 years [1]. Although hospital-based African studies indicate ectopic pregnanECTOPIC PREGNANCY: A NIGERIAN URBAN EXPERIENCE Etuknwa Bassey Tom, FRCS, Azu Onyemaechi Okpara, PhD, Peter Aniekan Imo, MD, Ekandem Gabriel John, PhD, Olaifa Kayode, BSc, Aquaisua Aquaisua Nyong, MSc, Ikpeme Enobong, MSc Department of Anatomy, College of Health Sciences, University of Uyo, Akwa Ibom State, Nigeria; Discipline of Clinical Anatomy, Nelson R Mandela School of Medicine, Durban, South Africa