Characterization of the structural, oxidative, and immunological features of testis tissue from Zucker diabetic fatty rats

Abstract

The purpose of this study was to characterize the testicular profile of Zucker diabetic fatty (ZDF) rats presenting with type 2 diabetes mellitus (DM2) in the absence or presence of obesity. To achieve this, testes were collected from 270-day-old male Wistar (n = 15), ZDF nonobese (n = 15), and ZDF obese rats (n = 16). Changes to the testicular structure were quantified morphometrically, while immunocytochemistry was employed to assess caspase-3 activity. Reactive oxygen species (ROS) production, fluctuations of major antioxidant molecules, and the extent of damage to the proteins and lipids were assessed in tissue lysates. Levels of selected interleukins (ILs) were determined by enzyme-linked immunosorbent assay. The results reveal significant alterations to the testicular structure accompanied by caspase-3 overexpression, particularly in ZDF obese rats. The most notable disruption of the oxidative balance, characterized by ROS overproduction, antioxidant deficiency, protein, and lipid deterioration was recorded in ZDF rats suffering from both DM2 and obesity. Accordingly, the highest concentrations of pro-inflammatory IL-1, IL-6, and IL-18 accompanied by reduced levels of the anti-inflammatory IL-10 were found in testicular tissue collected from ZDF obese rats. This study highlights the vulnerability of male gonads to pathophysiological changes caused by hyperglycemia, which are further exacerbated by excessive adipose tissue.

Quercetin Ameliorates Testicular Damage in Zucker Diabetic Fatty Rats through Its Antioxidant, Anti-Inflammatory and Anti-Apoptotic Properties

“…Alterations to testicular architecture are a common side effect of chronically elevated blood sugar or excessive accumulation of body fat. In accordance with our morphometric analysis in the untreated animals, previous reports observed that the induction of diabetes through medication or increased feed intake led to a reduced germ cell count and abnormalities to the spermatogenic series [22,23,29,30]. In particular, ZDF obese controls presented with a reduced cell layer with contracted and/or disarranged spermatogenic cells in the seminiferous tubules.…”

“…A reduced testicular weight in the Obese control observed in this study corroborates previous reports on diabetic rats [22][23][24] and may be explained by the loss of germ cells, inhibition of spermatogenesis, or a decline in the activity of steroidogenic enzymes necessary for a proper sperm production [23,25,26]. In the meantime, the testicular weights were increased following QUE supplementation in both experimental groups.…”

“…It is well known that male germ cells are more vulnerable to oxidative stress since their membranes contain excessive amounts of easily oxidable polyunsaturated fatty acids [38], providing explanation to the high MDA levels found in the controls. What is more, excessive ROS levels may trigger cell death through the apoptotic machinery [22,39,40], which correlates with our Western blot analyses. Oxidative stress may be aggravated in the presence of excessive body fat, as observed in our study.…”

“…Correspondingly to our morphometric outcomes, a recent meta-analysis published by Zhong et al [8] referred to experimental studies observing a deterioration of the seminiferous epithelium, occurrence of cellular debris, and germ cell detachment from the testicular basal lamina in obese individuals. At the same time, DM has been often accompanied by testicular atrophy and reduction of seminiferous tubules, all of which imply potential spermatogenic deficits [22,30,31]. On the other hand, neither Vendramini et al [23] nor Mansour et al [32] observed any significant differences in the morphometric features amongst ZDF Lean and Obese rats.…”

“…Consequently, the animals will suffer from a consistent hunger and develop obesity when fed, which will eventually be followed by the onset of Type 2 DM. As such, ZDF rats are considered to be a suitable model to study the pathophysiology of Type 2 DM and the effects of potential therapeutic strategies for the prevention or management of the disease [21,22].…”