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Updated: Jun 10, 2026
In vivo Characterization of Endocrine Disrupting Chemical Effects via Thyroid Hormone Action Indicator Mouse
Published on: October 6, 2023
T3 fails to restore mitochondrial thiol redox status altered by experimental hypothyroidism in rat testis
Sutapa Chattopadhyay1, Supragyanshree Choudhury, Anita Roy
1Department of Zoology, Utkal University, Bhubaneswar 751 004, India.
Abstract:
Oxidative stress impaired sperm function might lead to infertility. The objective of this study was to evaluate the effects of altered thyroid hormone levels on regulation of mitochondrial glutathione redox status and its dependent antioxidant defense system in adult rat testis and their correlation with testicular function. Adult male Wistar rats were rendered hypothyroid by administration of 6-n-propyl-2-thiouracil in drinking water for six weeks. At the end of the treatment period, a subset of the hypothyroid rats was treated with T(3) (20 μg/100g body weight/day for 3 days). Mitochondria were isolated from euthyroid, hypothyroid and hypothyroid+T(3)-treated rat testes, and sub-fractionated into sub-mitochondrial particles and matrix fractions. Mitochondrial respiration, oxidative stress indices and antioxidant defenses were assayed. The results were correlated with daily testicular sperm production and epididymal sperm viability. Increased pro-oxidant level and reduced antioxidant capacity rendered the hypothyroid mitochondria susceptible to oxidative injury. The extent of damage was more evident in the membrane fraction. This was reflected in higher degree of oxidative damages inflicted upon membrane lipids and proteins. While membrane proteins were more susceptible to carbonylation, thiol residue damage was evident in matrix fraction. Reduced levels of glutathione and ascorbate further weakened the antioxidant defenses and impaired testicular function. Hypothyroid condition disturbed intra-mitochondrial thiol redox status leading to testicular dysfunction. Hypothyroidism-induced oxidative stress condition could not be reversed with T(3) treatment.
Insights
Hypothyroidism impairs male fertility by increasing oxidative stress in rat testes, damaging mitochondria and sperm. Thyroid hormone (T3) treatment did not reverse these harmful effects, indicating a significant impact on reproductive health.
Area of Science:
- Reproductive Biology
- Endocrinology
- Oxidative Stress Research
Background:
- Oxidative stress is a known contributor to impaired sperm function and male infertility.
- Thyroid hormones play a crucial role in regulating various physiological processes, including testicular function.
Purpose of the Study:
- To investigate the impact of hypothyroidism on mitochondrial glutathione redox status and antioxidant defenses in rat testes.
- To correlate these changes with testicular function and sperm viability.
- To assess the reversibility of these effects with T3 treatment.
Main Methods:
- Adult male Wistar rats were made hypothyroid using 6-n-propyl-2-thiouracil.
- Mitochondria were isolated from testes of euthyroid, hypothyroid, and hypothyroid+T3 treated rats.
- Assays included mitochondrial respiration, oxidative stress markers, antioxidant capacity, and sperm parameters.
Main Results:
- Hypothyroidism increased oxidative stress and decreased antioxidant capacity in rat testicular mitochondria.
- Mitochondrial membrane lipids and proteins showed significant oxidative damage, particularly carbonylation.
- Reduced glutathione and ascorbate levels were observed, weakening antioxidant defenses and impairing testicular function.
- T3 treatment failed to reverse the hypothyroidism-induced oxidative stress and testicular dysfunction.
Conclusions:
- Hypothyroidism disrupts mitochondrial thiol redox status, leading to testicular dysfunction and impaired sperm production/viability.
- The observed oxidative damage in mitochondria is a key factor in hypothyroidism-related male infertility.
- Thyroid hormone replacement therapy (T3) was ineffective in reversing these detrimental effects in this model.
