Browsing by Author "Willemse, Chontrelle"

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    Cytotoxicity of methamphetamine exposure on sertoli cells: a pilot study with implications for male infertility
    (Taylor and Francis Ltd., 2025) Fisher, David; Zabida, Omar; Abdul-Rasool, Sahar; Willemse, Chontrelle
    Methamphetamine (Meth), a psychoactive drug, has been shown to reduce testicular weight and decrease sperm count, indicating its potential role in contributing to male infertility. We therefore assessed Meth’s effects (0.1–100 μM) on TM4 Sertoli cell viability, toxicity, and proliferation (trypan blue exclusion assay), mitochondrial activity (MA) (XTT assay), while transepithelial electrical resistance (TEER) was used to examine monolayer permeability. The acute study (only 24-hour Meth exposure) mimics recreational users and the chronic study, the Meth addicts who require daily doses (24–96 hours). Acute Meth treatment had minimal impact on TM4 Sertoli cell viability and toxicity, while chronic exposure resulted in reduced cell viability and increased toxicity in a dose-related manner. Acute exposure suppressed cell division at 72 hours, while chronic exposure suppressed cell division at both 72 and 96 hours. Long-term suppression of MA was observed for both acute and chronic Meth exposure (20 µM and 100 µM). Both acute and chronic Meth exposure affected permeability across the blood–testis barrier (BTB), which persisted for up to 96 hours. Given the pivotal role of Sertoli cells in spermatogenesis, our findings provide a two-pronged mechanism for Meth-induced male infertility and indicate that short-term exposure may have long-term effects on the germinal epithelium. © 2025 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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    HIV-1 viral protein effect on cerebral microvasculature: an in vitro blood–brain barrier model
    (American Physiological Society, 2025) Willemse, Chontrelle; Makhathini, Khayelihle Brian; Fisher, David
    The central nervous system (CNS) serves as a sanctuary for the Human Immunodeficiency Virus (HIV), which is facilitated by HIV's ability to breach the blood–brain barrier (BBB). BBB dysfunction occurs in the earliest stages of an HIV-1 infection. The immune-privileged CNS reduces harmful inflammatory responses, detrimental to the neuronal environment. BBB disruption, however, contributes to comorbidities in HIV, like cerebrovascular disease and neurocognitive problems. A 2-dimensional in vitro BBB model was employed to assess the effect of HL2/3 cell paracrine factors on select physiological parameters: cell proliferation, viability, toxicity, suppression, and morphology. BBB integrity was assessed using trans endothelial electrical resistance measurements. The study utilized immortalized mouse brain endothelial cell monocultures and co-cultures with the HL2/3 cell line, emulating an in vivo HIV-1 effect on the BBB.A concentration- dependent decline in cellular proliferation rates and viability was observed upon exposure to HL2/3 paracrine factors. Moreover, an elevation in cellular suppression, cell death, and cell toxicity was observed. Permeability studies confirmed decreased permeability after exposure to HIV-1 viral proteins in select in vitro BBB model systems. The impact of HIV viral proteins on brain capillary endothelium is critical to elucidate pathogen-induced cerebrovascular disease progression and vascular cognitive impairment in patients.