Proliferating Cell Nuclear Antigen as a Molecular Biomarker for Spermatogenesis in PTU-Induced Hypothyroidism of Rats

Abstract

The thyroid hormone has few serious effects on the testes except during the neonatal stage. There is little knowledge concerning the prolonged effect of thyroid hormone deficiency throughout the rat's life span and its effect on spermatogenesis. Proliferating cell nuclear antigen (PCNA) is a nuclear matrix protein, which is essential for multiple cell cycle pathways. Here we used PCNA immunohistochemistry as a marker to differentiate between the testes of control and hypothyroid rats. About 20 rats were equally divided into 2 groups; the first group was the control group, while the second group was the experimental group in which rats were fed 0.05% 6-n-propyl thiouracil (PTU) in drinking water for 6 weeks. Immunohistochemistry, using an antibody against PCNA, showed at least 3 differences in the pattern of PCNA immunoreactivity (PCNA-ir). First, PCNA-ir was not detected in Sertoli and Leydig cells in the testes of control rats and detected in some of the hypothyroid rats. Second, in the control group more than 96% of spermatogonia were PCNA-positive cells; however, hypothyroidism caused the reduction to approximately 25% PCNA staining in spermatogonia. The third difference was in the abnormal distribution of spermatogonia seen in the hypothyroid rat testis, not in the control one. These results suggest that prepubertal hypothyroidism affects the proliferation of spermatogenic cells leading to impaired spermatogenesis and that PCNA index is a useful marker for assessing germ cell kinetics and spermatogenesis in prepubertal hypothyroidism.

Folic Acid Alleviates Oxidative Stress and Hyperhomocysteinemia Involved in Liver Dysfunction of Hypothyroid Rats

“…The decrease in body weight gain was associated with a reduction in food and fluid consumption in groups of hypothyroidism. These findings are compatible with the results of other studies [11].…”

“…In order to achieve this target we made a hypothyroid state by using a reversible goitrogen (PTU) that known to decrease the conversion of peripheral T 4 to T 3 and thereby reduce serum T 3 concentration [4,5,8,11,33]. Hypothyroid state was documented by changes in T 3 and TSH.…”

“…Group 3: (G 3 ) Hypothyroid rats group in which, rats received 0.05% 6-n-propyl-2-thiouracil (PTU) in drinking water for 6 weeks according to Tousson et al [11].…”

“…Additionally, complex changes in folic acid metabolism occur in thyroid dysfunction with increases in tetrahydrofolate and decreases in methyltetrahydrofolate in hypothyroid rat liver [9]. Alteration in thyroid hormone level is also known to modulate functions of several tissues in adult animals by modulating their antioxidant defenses [4][5][6][7][8][10][11][12][13]. Overt Thyroid dysfunctions are frequently associated with abnormalities of biochemical liver tests and in severe forms with histologically evident hepatocellular damage the activity of hepatic lipase is decreased [14].…”

Impact of ginger aqueous extract on carbimazole induced testicular degenerative alterations and oxidative stress in albino rats

“…The ratio of Bcl-2/Bax in hippocampus neurons of hypothyroid pups was lower than that of age-matched controls. Treating rats with propylthiouracil caused 25% reduction in PCNA staining in spermatogonia; however, in the control group more than 96% of spermatogonia were PCNA-positive cells [30]. A significant decrease in PCNA staining was found in psoriatic epidermis patients after treatment of with propylthiouracil and methimazole [31].…”