## 4 Discussion
We recorded significant decreases in the luteinizing hormone (LH) (except for the DM+A group) and testosterone (TT) levels in all treated groups, particularly in the DM+A+cART group. There were significantly increased levels of follicle-stimulating hormone (FSH) and insignificant increases in inhibin B (INHB) levels in all treated groups, except for the DM+cART group, which showed a nonsignificant increase in FSH and a decrease in the INHB level. These perturbations of the hormonal profile reflect disturbances of endocrine homeostasis [43]. In addition, high levels of FSH indicate an impairment of testis function, particularly in relation to the Sertoli cells that secrete INHB, which regulates FSH production [68]. Many similarities and discrepancies exist in hormonal profile results, with increased levels of LH and FSH [69] and LH and TT [70] shown in diabetic individuals; decreased levels of TT shown in diabetics [71], alcohol consumers [16], and cART users [72];and decreased FSH levels shown in diabetics [51]. Remarkably, [PERSON] et al., 2020 [73] found that Sertoli cells exposed to bisphenol A had increased INHB production. While such observed hormonal imbalances may reflect differences in the research design, methods, and duration of treatment exposure, they all express adverse functional perturbations of the HPG axis. Furthermore, the balance among the HPG axis hormones is regulated via a negative feedback mechanism, whereby the TT and INHB hormones produced by testicular cells (Leydig and Sertoli cells respectively) modulate the pituitary secretion of LH and FSH, respectively [67; 74]. Conversely, decreased levels of both LH and TT and an increase in the FSH level when the level of INHB is not reduced, as observed in this study, might imply that the treatments have disrupted the HPG axis feedback mechanism. Additionally, the recorded hormonal imbalances conform with the observed Sertoli and Leydig cell perturbations and consequently lead to spermatogenesis and steroidogenesis impairments. Furthermore, human studies have reported altered reproductive hormone profiles in HIV-infected males under antiretroviral therapy [75; 76], which is associated with the high prevalence of gynecomastia and sexual dysfunction in this category of patients [77]. In addition, factors associated with a poor sperm quality, including reduced ejaculate volume and sperm motility, spermatozoa dysmorphology, and increased sperm nuclear fragmentation were recorded following long-term treatment with cART [78; 79]. Conversely, although the impact of changes in the levels of reproductive hormones has been studied extensively in relation to male reproductive dysfunction, investigations on the changes in their receptors are scant, despite their vital roles in successful male reproduction and fertility [44; 67]. The androgen receptor is expressed by testicular somatic cells, such as Leydig, Sertoli, myoid, and perictyte cells, and it regulates the structures and functions of these cells and mediates the actions of TT on spermatogenesis [80; 81]. The observed significant reductions in the number and staining intensity of Sertoli and Leydig cells expressing the androgen receptor in all treated groups and, interestingly, the more severe losses recorded in the diabetes-alcohol treated group (DM+A), are suggestive of testicular toxicity and consequent dysfunction. Our findings are consistent with previous reports on decreased androgen receptor expression in diabetic rat testes, resulting in weak androgen receptor signaling and leading to testicular and sexual dysfunction [82; 83]. Other studies on organochlorinated pesticides, industrial chemicals, and plasticizers have reported similar testicular toxic effects [28; 84], including several seminiferous tubule impairments in rats treated with the diacreein drug [85]. Moreover, hypocellular testes with the arrest of spermatogenesis were reported in androgen-receptor-knockout animal models [81; 86].