Assessment of developmental effects of hypothyroidism in rats from in utero and lactation exposure to anti-thyroid agents

Shibutani, Makoto; Woo, Gye‐Hyeong; Fujimoto, Hitoshi; Saegusa, Yukie; Takahashi, Miwa; Inoue, Kaoru; Hirose, Masao; Nishikawa, Akiyoshi

doi:10.1016/j.reprotox.2009.04.011

Cited by 77 publications

(47 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…3A, B). We observed effects of PTU on body weight and testicular weight of F 1 male pups, consistent with previous reports using antithyroid agents (Kirby et al, 1992;Kimura and Furudate, 1996;Shibutani et al, 2009). The relative testis weight was paradoxically increased in a dose-dependent manner after 7 weeks of age.…”

Section: Discussionsupporting

confidence: 91%

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

et al. 2014

View full text Add to dashboard Cite

-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.

show abstract

Section: Discussionsupporting

confidence: 91%

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

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Considering the role of reelin in regulating migration and correct positioning of developing neurons (Rice and Curran, 2001), this result suggested a compensatory mechanism for the impaired neurogenesis and mismigration caused by exposure to thyroid hormone-disrupting chemicals during neuronal development. However, developmental hypothyroidism also causes a suppression of systemic growth (Shibutani et al, 2009). Systemic growth suppression causes delayed brain growth that may result in affection of neurogenesis.…”

Section: Introductionmentioning

confidence: 99%

Adolescent hyperactivity of offspring after maternal protein restriction during the second half of gestation and lactation periods in rats

et al. 2012

Self Cite

View full text Add to dashboard Cite

-To clarify the effect of systemic growth retardation on behavior, pregnant rats were fed a synthetic diet with either a normal (20% casein) or low (10% casein) protein concentration from gestational day 10 to postnatal day (PND) 21 at weaning. Offspring were examined for sensory and reflex functions, detailed clinical observations, manipulative test, grip strength, motor activity and water-filled multiple T-maze test. Lowering trend in the air righting reflex index during lactation period and a decrease in grip strength on PND 72 were observed in the low protein diet group showing suppression of systemic growth. However, they were simply the reflection of delayed systemic growth, because parameters on impaired reflex function, disturbance of motor function and paralysis were unaffected. On the other hand, low protein diet resulted in increased motor activity in female offspring. Thus, malnutrition due to maternal protein restriction may cause adolescent hyperactivity.

show abstract

“…Antagonists, which are much more frequently identified because of the multiple mechanisms that can lead to decreased circulating thyroid hormones (and also due to the particular susceptibility of rats to this effect) usually show a pattern of feedback-related changes including T4 decreases and/or T3 decreases and feedback-mediated TSH increases, which typically result in follicular cell hypertrophy of the thyroid gland, thyroid gland weight increases and follicular cell hyperplasia (Marty et al 2001). Potent anti-thyroid agents may also result in developmental neurotoxicity if exposures are pre-or peri-natal (see for example Goldey et al 1995;Shibutani et al 2009;Bernal 2012).…”

Section: Woe Evaluation For Potential Effects Of 24-d On the Hpt Axismentioning

confidence: 99%

Weight-of-the-evidence evaluation of 2,4-D potential for interactions with the estrogen, androgen and thyroid pathways and steroidogenesis

Neal

Marty

Coady

et al. 2017

Critical Reviews in Toxicology

View full text Add to dashboard Cite

A comprehensive weight-of-the-evidence evaluation of 2,4-dichlorophenoxyacetic acid (2,4-D) was conducted for potential interactions with the estrogen, androgen and thyroid pathways and with steroidogenesis. This assessment was based on an extensive database of high quality in vitro, in vivo ecotoxicological and in vivo mammalian toxicological studies. Epidemiological studies were also considered. Toxicokinetic data provided the basis for determining rational cutoffs above which exposures were considered irrelevant to humans based on exceeding thresholds for saturation of renal clearance (TSRC); extensive human exposure and biomonitoring data support that these boundaries far exceed human exposures and provide ample margins of exposure. 2,4-D showed no evidence of interacting with the estrogen or androgen pathways. 2,4-D interacts with the thyroid axis in rats through displacement of thyroxine from plasma binding sites only at high doses exceeding the TSRC in mammals. 2,4-D effects on steroidogenesis parameters are likely related to high-dose specific systemic toxicity at doses exceeding the TSRC and are not likely to be endocrine mediated. No studies, including high quality studies in the published literature, predict significant endocrine-related toxicity or functional decrements in any species at environmentally relevant concentrations, or, in mammals, at doses below the TSRC that are relevant for human hazard and risk assessment. Overall, there is no basis for concern regarding potential interactions of 2,4-D with endocrine pathways or axes (estrogen, androgen, steroidogenesis or thyroid), and thus 2,4-D is unlikely to pose a threat from endocrine disruption to wildlife or humans under conditions of real-world exposures.ARTICLE HISTORY

show abstract

Assessment of developmental effects of hypothyroidism in rats from in utero and lactation exposure to anti-thyroid agents

Cited by 77 publications

References 43 publications

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

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

Adolescent hyperactivity of offspring after maternal protein restriction during the second half of gestation and lactation periods in rats

Weight-of-the-evidence evaluation of 2,4-D potential for interactions with the estrogen, androgen and thyroid pathways and steroidogenesis

Contact Info

Product

Resources

About