Impact of Concurrent Exposure of Diabetic Male Sprague Dawley Rats to Alcohol and Combination Antiretroviral Therapy (cART) on Reproductive Capacity

Abstract

The prevalence of diabetic patients who abuse alcohol while on combination antiretroviral drug therapy (cART) therapy is rising in society. Little is known about the impact of this scenario on the testes and male reproductive viability, and therefore, these factors were evaluated. Thirty 10-week-old male Sprague Dawley rats were distributed into five groups of six rats each: control, diabetic only (DM), diabetic treated with alcohol (DM+A), diabetic treated with Atripla, fixed-dose cART (DM+cART), and diabetic treated with both alcohol and cART (DM+A+cART). After 90 days of treatment, rats were terminated, and blood and testes were harvested for immunoassay, histological, and immunohistochemistry analyses. Testicular perturbations of varying severity were recorded in all treated groups for most of the parameters. The DM+A treated group showed the most severe perturbations, followed sequentially by the treated groups DM+A+cART, DM, and DM+cART. Alterations in the testes and seminiferous tubule morphometry as well as the spermatogenic, Sertoli, and Leydig cells were found in all treated groups. Further, a significant decrease in Johnsen’s testicular scores, the appearance of seminiferous tubule lesions, changes in the basement membrane and capsule thickness, and a reduction in the testis connective tissue fibers were demonstrated in the treated groups. Additionally, reproductive hormone levels were altered, and the number and staining intensity of Sertoli and Leydig cells expressing androgen receptors reduced significantly in all treated animals. The study results reveal that the consumption of alcohol and/or the use of cART in diabetic individuals induces a derangement in circulating reproductive hormone levels and in the testicular structure and function, which consequently leads to a decline in the male reproductive capacity.