Use of Atomic Force Microscopy to Reveal Sperm Ultrastructure in Hiv-Patients on Highly Active Antiretroviral Therapy

Barboza, José M.; Medina, Honorio; Doria, Margherita; Rivero, Luz Amira; Hernández, L.M. Calvo; Joshi, N.V.

doi:10.1080/aan.50.2.121.129

Cited by 28 publications

(4 citation statements)

References 11 publications

(1 reference statement)

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“…Although RDs are part of HIV complications widely reported in the literature before introducing highly active antiretroviral therapy (HAART) 2 , 3 . Nevertheless, the roll-out of HAART since the mid-80s and to date, antiretroviral therapy is now perceived as a direct or indirect cause of RDs via various mechanisms of action 4 , 5 . Among several adverse effects of HAART are insulin resistance and type 2 diabetes mellitus (T2DM), which were documented as HIV-1 therapeutic detrimental effects, especially HAART 6 .…”

Section: Introductionmentioning

confidence: 99%

Testicular ultrastructure and hormonal changes following administration of tenofovir disoproxil fumarate-loaded silver nanoparticle in type-2 diabetic rats

Olojede

Lawal

Faborode

et al. 2022

Sci Rep

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Reproductive dysfunctions (RDs) characterized by impairment in testicular parameters, and metabolic disorders such as insulin resistance and type 2 diabetes mellitus (T2DM) are on the rise among human immunodeficiency virus (HIV) patients under tenofovir disoproxil fumarate (TDF) and highly active antiretroviral therapy (HAART). These adverse effects require a nanoparticle delivery system to circumvent biological barriers and ensure adequate ARVDs to viral reservoir sites like testis. This study aimed to investigate the effect of TDF-loaded silver nanoparticles (AgNPs), TDF-AgNPs on sperm quality, hormonal profile, insulin-like growth factor 1 (IGF-1), and testicular ultrastructure in diabetic rats, a result of which could cater for the neglected reproductive and metabolic dysfunctions in HIV therapeutic modality. Thirty-six adult Sprague–Dawley rats were assigned to diabetic and non-diabetic (n = 18). T2DM was induced by fructose-streptozotocin (Frt-STZ) rat model. Subsequently, the rats in both groups were subdivided into three groups each (n = 6) and administered distilled water, TDF, and TDF-AgNP. In this study, administration of TDF-AgNP to diabetic rats significantly reduced (p < 0.05) blood glucose level (268.7 ± 10.8 mg/dL) from 429 ± 16.9 mg/dL in diabetic control and prevented a drastic reduction in sperm count and viability. More so, TDF-AgNP significantly increased (p < 0.05) Gonadotropin-Releasing Hormone (1114.3 ± 112.6 µg), Follicle Stimulating Hormone (13.2 ± 1.5 IU/L), Luteinizing Hormone (140.7 ± 15.2 IU/L), testosterone (0.2 ± 0.02 ng/L), and IGF-1 (1564.0 ± 81.6 ng/mL) compared to their respective diabetic controls (383.4 ± 63.3, 6.1 ± 1.2, 76.1 ± 9.1, 0.1 ± 0.01, 769.4 ± 83.7). Also, TDF-AgNP treated diabetic rats presented an improved testicular architecture marked with the thickened basement membrane, degenerated Sertoli cells, spermatogenic cells, and axoneme. This study has demonstrated that administration of TDF-AgNPs restored the function of hypothalamic-pituitary–gonadal axis, normalized the hormonal profile, enhanced testicular function and structure to alleviate reproductive dysfunctions in diabetic rats. This is the first study to conjugate TDF with AgNPs and examined its effects on reproductive indices, local gonadal factor and testicular ultrastructure in male diabetic rats with the potential to cater for neglected reproductive dysfunction in HIV therapeutic modality.

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Section: Introductionmentioning

confidence: 99%

Testicular ultrastructure and hormonal changes following administration of tenofovir disoproxil fumarate-loaded silver nanoparticle in type-2 diabetic rats

Olojede

Lawal

Faborode

et al. 2022

Sci Rep

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“…Similar clinical cohort and in vivo studies have documented a deleterious effect of TDF on semen and sperm indices such as count, motility, and morphology [ 45 – 47 ]. Previous studies have implicated highly active antiretroviral therapy in various reproductive perturbations such as a significant decrease in sperm count, alteration to spermatozoa, and increased abnormal sperm forms [ 48 , 49 ]. All these findings taken together, indicate the adverse effect of TDF on sperm indices and morphology.…”

Section: Discussionmentioning

confidence: 99%

Histomorphometric changes in testis following administration of tenofovir nanoparticles in an animal model

Naidu,

Olojede,

Lawal

et al. 2024

Discover Nano

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Background Nanoparticle-based drugs are new inventions in the management of the Human immunodeficiency virus (HIV) pandemic, especially resistant forms of the virus in anatomical sanctuary sites and organs such as the testis. However, safety issues must be resolved to attain the optimal potential of newer nano-drug formulations. Aim The study investigated the toxicological potential of synthesized Tenofovir Nanoparticles (TDF-N) on testicular indices when used for the prevention and treatment of HIV. Methodology Fifteen male Sprague–Dawley (SD) rats with weight ranging from 230 g to 250 g were randomly assigned into groups A (control, saline), B (TDF), and C (TDF-N). The testes were removed for sperm analysis and processed for H/E and PAS stains. Cell counts and cellular measurements; the diameter and the area of the testicular seminiferous tubules were measured using ImageJ and Leica software 2.0. Results A significant reduction (p < 0.05) in sperm count was noticed in the TDF-N group. Also observed in the TDF and TDF-N groups was a significant reduction (p < 0.05) in sperm motility and in the number of dead sperms compared with the control. Sperm abnormalities such as distorted basement membranes, loss of germ cells, hypocellular interstitium, and loss of spermatogenic series were increased in the TDF and TDF-N groups. There was also a significant reduction (p < 0.05) in the cell count, diameter, and area of seminiferous tubules observed in these groups. Conclusion TDF and TDF-N may be detrimental to the testis and testicular tissue, leading to significantly reduced sperm counts, motility, and ultimately–male fertility.

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“…The study concluded that spermatozoa damage was due to antiretroviral drug exposure, and not the result of the HIV virus itself. 63 The impact of antiretroviral drugs on the fertility of female adults is more complex. In adult women living with HIV, low mitochondrial DNA levels in oocytes, a dysfunction typically associated with infertility, has been reported.…”

Section: Cart and Changes In Pregnancymentioning

confidence: 99%

The Impact Of Human Immunodeficiency Virus (HIV) Antiretroviral Drug Exposure In-Utero On Later Fertility

Zafar¹

2023

Preprint

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<p>Combination antiretroviral therapy (cART) reduces the risk of vertical human immunodeficiency virus (HIV) transmission. Two nucleoside reverse transcriptase inhibitors (NRTIs) are usually included in cART. The efficacy of cART has been extensively studied, but a significant knowledge gap exists concerning the effects of in-utero exposure on developing fetuses. In this project, we assessed the effects of HIV antiretrovirals on the reproductive health of offspring. Using Schizosaccharomyces pombe, we have shown that mutagenicity, but not toxicity, increases over time after dual-NRTI exposure. Our mouse pregnancy model suggests that in-utero cART exposure does not affect female germ cell development but alters the testes structure, thus adversely impacting male germ cell development. However, our study is limited in sample size and we aim to improve this by quantifying more gonad sections. Ultimately, we hope to provide more insight on the potential long-term fertility issues faced by children exposed inutero to antiretrovirals. </p>

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Use of Atomic Force Microscopy to Reveal Sperm Ultrastructure in Hiv-Patients on Highly Active Antiretroviral Therapy

Cited by 28 publications

References 11 publications

Testicular ultrastructure and hormonal changes following administration of tenofovir disoproxil fumarate-loaded silver nanoparticle in type-2 diabetic rats

Testicular ultrastructure and hormonal changes following administration of tenofovir disoproxil fumarate-loaded silver nanoparticle in type-2 diabetic rats

Histomorphometric changes in testis following administration of tenofovir nanoparticles in an animal model

The Impact Of Human Immunodeficiency Virus (HIV) Antiretroviral Drug Exposure In-Utero On Later Fertility

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