Abstract
Objectives: Dysfunction of the thyroid gland has a negative effect on the male reproductive system. Studies also show that extracellular matrix (ECM) components play an essential role in testicular development and function. In hypothyroidism, there is a significant disruption in the ECM structure of mammalian tissues. In addition, notable changes have been reported in the germ cell population under a hypothyroid state. This study aimed to investigate the relationship between ECM proteins and apoptosis of testicular germ cells due to hypothyroidism. Materials and Methods: In the present experimental study, 20 male Balb/C mice were divided into control and hypothyroid groups. The hypothyroid group received 0.05% 6-n-propyl-2-thiouracil (PTU) through drinking water for 35 days. Finally, real-time polymerase chain reaction, immunohistochemistry, periodic acid-Schiff (PAS) staining, terminal transferase-mediated dUTP nick-end labelling (TUNEL) assay, and biochemical measurements were performed after hypothyroidism confirmation. Results: Laminin α5 and collagen IV mRNA levels were upregulated in the hypothyroid group compared to the controls (P<0.05). Further, a strong immunoreactivity of collagen IV and laminin α5 was observed in the basement membrane (BM) of hypothyroid mice (P<0.05). In contrast, there was no significant difference between the case and control groups regarding PAS staining. The number of TUNEL-positive germ cells in hypothyroid mice increased significantly compared to control mice. Moreover, PTU administration reduced superoxide dismutase activity while increasing the malondialdehyde level (P<0.05). Eventually, no significant difference was found between the two groups in terms of thiol content. Conclusions: Based on the results of the present study, hypothyroidism can cause changes in BM components and increase the apoptosis of germ cells by inducing lipid peroxidation and reducing the activity of antioxidant defense molecules.
Highlights
The most important roles of thyroid hormone (TH) are the regulation, differentiation, metabolism, and normal function of body tissues [1,2,3]
Serum Hormones Profile Based on the findings of the study, the serum levels of total T4 remained low in the hypothyroid group compared to the control group whereas the Thyroid-stimulating hormone (TSH) level increased in the hypothyroid group in comparison to the controls, confirming the hypothyroid status of PTU-administered mice (Table 2, P < 0.05)
The results showed that the levels of laminin α5 mRNA in the hypothyroid group significantly increased compared to the control group (P < 0.001, Figure 1A)
Summary
The most important roles of thyroid hormone (TH) are the regulation, differentiation, metabolism, and normal function of body tissues [1,2,3]. Functional and anatomical changes of the thyroid gland cause different kinds of hypothyroidism [7,8]. A large body of data indicates that an altered thyroid status in mammals adversely affects many organs and tissues [9]. It was long thought that the testis was an unresponsive tissue to TH, studies in the past two decades have shown that it is a hormoneresponsive organ, and TH is important in the regulations of growth, proliferation, and differentiation of Sertoli, germ, and Leydig cells and testicular functions [1,2]. In several reports, disturbance in the TH could adversely affect male fertility and spermatogenesis [1,10]
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