OGBE, ONOME CLEMENTINA

EFFECTS OF TENOFOVIR DISOPROXIL FUMURATE/LAMIVUDINE/ DOLUTEGRAVIR (TLD) ON THE HISTOMORPHOMETRIC AND REPRODUCTIVE PARAMETERS OF THE OVARY, UTERUS, AND PLACENTA OF ADULT WISTAR RATS

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Abstract
Human Immunodeficiency Virus (HIV) infection remains one of the leading causes of morbidity and mortality worldwide. Since the beginning of the epidemic, approximately ninety-one million four hundred thousand people have been infected with HIV, and about forty-four million one hundred thousand have died from AIDS-related illnesses. Globally, in 2024, forty million eight hundred thousand people were living with HIV, six hundred thirty thousand people died from AIDS-related illnesses, and one million three hundred thousand people were newly infected with HIV. Tenofovir Disoproxil Fumarate/ Lamivudine/Dolutegravir (TLD) is one of the therapeutic regimens used in the management of HIV infection. This study assessed the effects of TLD on the histomorphometric and reproductive parameters of the ovary, uterus, and placenta of adult Wistar rats. A total of fifty adult female Wistar rats, weighing between 140 g and 194 g, were used for the study. The rats were randomly assigned to control and treated groups, consisting of twenty-five rats, and were further subdivided into five subgroups of five rats each. Both groups received growers mash and distilled water; however, the treated group was administered a daily oral dose of a combination drug consisting of Tenofovir Disoproxil Fumarate (5 mg/kg body weight), Lamivudine (5 mg/kg body weight), and Dolutegravir (0.8 mg/kg body weight) via an orogastric tube. After ninety days of TLD administration, animals with regular four-day estrous cycles were weighed and mated. The animals were categorized into pregestational, gestational, and postnatal groups. The pregestational group was used to evaluate the effects of TLD on antioxidant status, hormonal profile, and histomorphometry of the ovary and uterus. The gestational group was used to assess implantation/resorption, and placenta parameters, while the postnatal group was used to evaluate litter size, litter weight, intrauterine and neonatal death, growth retardation, and congenital anomalies. This study reveals that TLD treatment resulted in a significant decrease in body weight (p < 0.05) but did not significantly affect ovarian, uterine weights and uterine horn length (p > 0.05). Ovarian antioxidant status showed no significant changes; however, the uterus exhibited reduced malondialdehyde (MDA) levels and increased superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities. The placenta showed significantly reduced glutathione (GSH) levels. Serum testosterone levels were significantly reduced (p < 0.05). No significant differences were observed in litter number, implantation sites, or number of placenta (p > 0.05). However, litter size and placenta weights were significantly reduced, with evidence of intrauterine growth retardation and low birth weight. Histological findings revealed impaired follicular maturation characterized by atretic follicles, follicular and luteal cysts, narrowing of the endometrial cavity, and thickened endometrium in the treated group. Additionally, dilation, congestion, and vacuolation of the feto-maternal vascular bed were observed. In conclusion, TLD exerted notable adverse effects on reproductive parameters in female Wistar rats, suggesting the need for caution in its use among women of reproductive age
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