Dose-dependent effects of perinatal hypothyroidism on postnatal testicular development in rat offspring

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 SpragueDawley 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.

EDC IMPACT: Reduced sperm counts in rats exposed to human relevant mixtures of endocrine disrupters

“…However, that would be expected to persist into adulthood, which was not the case in the present study. Altered Sertoli cell maturation was described in rat offspring perinatally exposed to the thyrotoxic compound propylthiouracil (PTU), but in contrast to the current study, increased testis weights in PTU-exposed animals persist into adulthood ( 44 ), and sperm counts increase ( 45 ). Other mechanisms including changes in fluid dynamics may be included, and our observations warrant further studies on how early endocrine-mediated changes in testicular development may have late-life consequences, and how chemicals with different effect patterns in prepuberty can induce similar late-life reductions of sperm count.…”

α-lipoic acid inhibits oxidative stress in testis and attenuates testicular toxicity in rats exposed to carbimazole during embryonic period

“…Further, there is a major concern towards the usage of antithyroid drugs in pregnant women, because these drugs can readily cross the placenta and affect fetal development [1] . Rodent studies indicated that perinatal exposure to CBZ causes disorganization of thyroid gland [7] and administration of PTU and MMI during the pre- (via the placenta) and peri-natal (via the placenta and through the milk) periods not only resulted in neurotoxicity [8] but also caused testicular and epididymal toxicity accompanied by the reduced serum testosterone levels [9] , [10] , [11] , [12] , [13] . Further, studies of Calanis-Continente et al [4] reported the clinical history of a woman with a necrotizing glomerulonephritis and pulmonary hemorrhage associated with CBZ therapy.…”

Low dose of flurochloridone affected reproductive system of male rats but not fertility and early embryonic development

“…Although FLC caused damage to the sperm, there was no change in mating rate and pregnancy rate in each dose group in our study, probably because the number of sperm produced by rodents far exceeded the minimum requirements for fertility. It was found that Sperm quality played an important role in determining human fertility [30, 31]. Decreased sperm motility and morphology were significant predictive factors for high sperm DNA damage [29], as in vivo fecundity decreased progressively when > 30% of the sperm were identified as having DNA damage [28].…”