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Dose-dependent effects of perinatal hypothyroidism on postnatal testicular development in rat offspring
Kenichi Kobayashi1, Hisayo Kubota, Rieko Hojo
1National Institute of Occupational Safety and Health.
Insights
Perinatal exposure to 6-propyl-2-thiouracil (PTU) temporarily reduced body weight and testicular size in male rats. However, adult rats showed dose-dependent testicular enlargement, with larger seminiferous tubules and more Sertoli cells.
Area of Science:
- Endocrinology
- Reproductive Biology
- Developmental Toxicology
Background:
- Thyroid hormones are crucial for mammalian development, but their precise role in gonadogenesis is not fully elucidated.
- Perinatal thyroid hormone levels can significantly impact reproductive system development and function.
Purpose of the Study:
- To investigate the dose-related effects of transient perinatal hypothyroidism on male rat reproductive development.
- To understand the long-term consequences of developmental thyroid hormone disruption on testicular parameters.
Main Methods:
- Timed-pregnant Sprague-Dawley rats were administered varying doses of 6-propyl-2-thiouracil (PTU) from gestational day 15 to postnatal day 20.
- Offspring were assessed for body weight, testicular and epididymis weight, hormone levels (thyroxine, triiodothyronine, testosterone), and testicular histology up to 26 weeks of age.
Main Results:
- PTU exposure caused a dose-dependent decrease in body weight up to 13 weeks, with recovery by 26 weeks.
- Testicular weight was reduced early but increased in adulthood, showing a paradoxical dose-dependent enlargement.
- Histological analysis revealed larger seminiferous tubules with increased Sertoli cell numbers and initially reduced Leydig cell numbers in PTU-exposed rats.
Conclusions:
- Transient perinatal thyroid hormone suppression leads to early-life testicular changes but results in paradoxical dose-dependent testicular enlargement in adult male rats.
- The observed adult testicular changes are associated with increased seminiferous tubule size and elevated Sertoli cell populations, suggesting compensatory mechanisms or altered developmental trajectories.
Abstract:
The role of thyroid hormones in gonad development remains incompletely understood. We examined the dose-related effects of perinatal hypothyroidism induced by a reversible goitrogen, 6-propyl-2-thiouracil (PTU), on reproductive development in male rat offspring. Timed-pregnant Sprague-Dawley rats were orally administered PTU (0, 0.5, 1.0, or 2.0 mg/kg/day) by gavage from gestational day 15 through postnatal day 20. We observed a significant dose-dependent decrease in body weight in offspring with PTU exposure up to 13 weeks of age, but body weight became comparable among groups by 26 weeks of age. Testicular weight tended to be lower up to 7 weeks but was higher after 13 weeks of age. Epididymis weight was not different among the groups at any age. Plasma concentrations of thyroxine and triiodothyronine in the PTU groups were significantly lower at 3 weeks of age but recovered to normal levels by 26 weeks of age. No dose-related trend in plasma testosterone concentrations was found. Seminiferous tubules were larger at 13 and 26 weeks of age with PTU exposure. The number of Sertoli cells was significantly higher from 3 through 26 weeks of age. The number of Leydig cells was significantly lower up to 7 weeks of age but was comparable among groups from 13 weeks of age onwards. Thus, transient gestational and lactational thyroid hormone suppression induced small testes in early life but led to paradoxical dose-dependent testicular enlargement in adults as indicated partly by larger seminiferous tubules with numerous Sertoli cells in male rat offspring.
