Irreversible damage to auditory system functions caused by perinatal hypothyroidism in rats

Wada, Hiromi; Yumoto, S.; Iso, Hiroyuki

doi:10.1016/j.ntt.2013.02.006

Cited by 9 publications

(12 citation statements)

References 28 publications

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“…High-pressure air flow from the thorax has been shown to create USVs by passing through a small orifice of the closed vocal folds (Brudzynski and Fletcher, 2010). Hypothyroidism has been shown to inhibit body weight gain and delay physical development in this and other studies (Schneider and Golden, 1987;Albee et al, 1989;Henck et al, 1996;Wada et al, 2013). Lower body weights could cause a reduction in the volume of thorax and breast muscles necessary to create high-pressure air flow.…”

Section: Before Auditory Function Onsetmentioning

confidence: 75%

“…Animal model studies demonstrated irreversible damage to auditory functions in rats as a result of perinatal hypothyroidism (Comer and Norton, 1982;Albee et al, 1989;Knipper et al, 2000;Wada et al, 2013). Comer and Norton (1982) treated 0.1 mg/ml MMI in drinking water.…”

Section: After Auditory Function Onsetmentioning

confidence: 99%

“…In addition, the amplitude of startle responses is reduced (Goldey et al, 1995;Henck et al, 1996). Irreversible damage to auditory functions was demonstrated (Wada et al, 2013); severe hearing deficits were detected over a wide range of tone frequencies from 1 to 40 kHz (Goldey et al, 1995). Hearing deficits make it difficult for rats to hear their own vocalizations and those of their conspecifics.…”

Section: Introductionmentioning

confidence: 99%

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Acoustic alterations of ultrasonic vocalization in rat pups induced by perinatal hypothyroidism

Wada

2017

NeuroToxicology

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Perinatal hypothyroidism causes serious damage to auditory functions that are essential for vocalization development. In rat pups, perinatal hypothyroidism potentially affects the development of ultrasonic vocalization (USV) as a result of hearing deficits. This study examined the effect of perinatal hypothyroidism on the development of USVs in rat pups. Twelve pregnant rats were divided into three groups and treated with the anti-thyroid drug methimazole (MMI) via drinking water, from gestational day 15 to postnatal day (PND) 21. The MMI concentration (w/v) was 0% (control group), 0.01% (low-dose group), or 0.015% (high-dose group). After birth, the pups were individually separated from the dam and littermates on PNDs 5, 10, 15, and 20, and their USVs were recorded for 5min. On PNDs 5 and 10, compared with the control group, the low- and high-dose groups exhibited reductions of both frequency-modulated and downward USVs. On PND 15, however, the low- and high-dose groups displayed increases in number, duration, and amplitude of USVs compared with those in the control group. Lower body weights were observed for the low- and high-dose groups than for the control group. Total thyroxine concentrations in plasma were dose-dependently reduced. The onset of auditory functions appeared on PNDs 11-14. Thus, the rat pups were unable to hear externally produced USVs before PND 11. USVs emitted on PNDs 5 and 10 might have been spontaneous and independent of the pups' own or littermate-emitted USVs. The developmental retardation of vocalization-related organs or muscles might underlie the acoustic alterations of USVs on PNDs 5 and 10. The greater number, duration, and amplitude of USVs on PND 15, after which the hearing onset occurred, suggested that the elevation of auditory thresholds occurred as a result of hearing deficits in the low- and high-dose groups. Perinatal hypothyroidism appears to have caused acoustic alterations in the USV development.

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Section: Before Auditory Function Onsetmentioning

confidence: 75%

Section: After Auditory Function Onsetmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Acoustic alterations of ultrasonic vocalization in rat pups induced by perinatal hypothyroidism

Wada

2017

NeuroToxicology

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“…Furthermore, multiple sensory inputs such as visual, auditory, olfactory, and tactile stimuli trigger maternal behavior ( 43 ). According to a study in rats, perinatal hypothyroidism results in irreversible damage to auditory function resulting in hearing loss ( 44 ); consequently, F1 mothers may not be able to hear ultrasonic vocalization or calls produced by pups that should have immediately induced retrieval ( 45 ). Because THs are responsible for the development of various neuronal and neuroendocrinological functions, PTU treatment during in utero and postnatal periods may have disrupted functional development of such systems even if it is mild or moderate.…”

Section: Discussionmentioning

confidence: 99%

In Utero and Postnatal Propylthiouracil-Induced Mild Hypothyroidism Impairs Maternal Behavior in Mice

et al. 2018

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Thyroid hormones (THs) play crucial roles in general and brain development. Even if the hypothyroidism is mild, it may alter brain function, resulting in irreversible behavioral alterations. Although various behavioral analyses have been conducted, the effects of propylthiouracil (PTU) treatment during in utero and postnatal periods on maternal behavior have not yet been studied. The present study examined in mice whether THs insufficiency during development induce behavioral changes. Pregnant C57BL/6j mice were divided into three groups, and each group was administered different dosages of PTU (0, 5, or 50 ppm) in drinking water during in utero and postnatal periods (from gestational day 14 to postnatal day 21). First, locomotor activity and cognitive function were assessed in the offspring at 10 weeks. Next, female offspring were mated with normal mice and they and their offspring were used to assess several aspects of maternal behavior (identifying first pup, returning all pups to nest, time spent nursing, and licking pups). As expected, locomotor and cognitive functions in these mice were disrupted in a PTU dose-dependent manner. On postpartum day 2, dams who had been exposed 50 ppm PTU during in utero and postnatal periods displayed a significantly longer time identifying the first pup and returning all three pups back to the nest, less time nursing, and decreased licking behavior. The decrease in maternal behavior was significantly correlated with a decrease in cognition. These results indicate that insufficiency of THs during in utero and postnatal periods impairs maternal behavior, which may be partly induced by impaired cognitive function.

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“…It has shown that perinatal thyroid dysfunction can lead to a significant reduction in body weight and height, delayed neurodevelopment, high risk of cognitive disorders and depression-like behaviors in infants (7). The evidence suggests an association between gestational hypopituitarism and impaired intellectual and cognitive development in offspring (8) and irreversible damage to the auditory system functions caused by perinatal hypothyroidism in rats (9). Considering this vital role played by maternal thyroid hormones on fetal neurodevelopment, our patient's first trimester thyroxine dose was increased from 100µg daily pre-conception to 125µg daily and later in the third trimester to 150µg daily to maintain a high normal free thyroxin concentration (>1.5ng/dl).…”

Section: Discussionmentioning

confidence: 99%

Successful twin pregnancy in panhypopituitarism

Jeewantha

Perera²,

Wijeyaratne

et al. 2015

Sri Lanka J. Diabetes Endocrinol. Metab.

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CaseA 35 year old mother of one admitted from our antenatal clinic at 34 weeks of period of gestation for the tertiary care management of a dichorionic diamniotic (DCDA) twin pregnancy.At the age of 20 years, she was diagnosed to have a Rathke's pouch cyst, which was surgically drained and followed by radiotherapy. Post-interventional panhypopituitarism was diagnosed and she was on hormone replacement for hypocortisolism, hypothyroidism and hypopogonadotropic hypogonadism; while growth hormone was not replaced due to lack of funding. She was replaced with oral levo-thyroxine, hydrocortisone (20mg daily in split doses) and the combined oral contraceptive pill (OCP). The patient remained symptomfree and returned to full time work. Upon her request, at the age of 28 years as fertility treatment, induction of ovulation with gonadotrophins was done. During the second cycle of treatment with recombinant FSH for follicular development and maturation with subsequent human chorionic gonadotrophin (hCG) for ovulation following ultrasound ovum tracking coupled, with Intra Uterine Insemination (IUI) resulted in a singleton intrauterine pregnancy. AbstractPanhypopituitarism is characterized by inadequate or absent production of anterior pituitary hormones. This involves hypofunction of most of the major endocrine functions that affect fertility and reproduction. Deficiency of all six anterior pituitary hormones leads to deficiencies of gonadotrophins (FSH, LH), thyroid axis (TSH), adrenocortical hormones (ACTH), Growth Hormone (GH) and Prolactin (PRL). GH and gonadotrophin deficiency are commoner (1) than TSH and ACTH deficiency (2).Although pregnancy after complete loss of pituitary function is uncommon, advances in fertility treatment have led to increased pregnancy rates in these women. Problems related to pregnancy include infertility, lactation failure and increased risk of complications such as miscarriage, anaemia, pregnancy-induced hypertension, placental abruption, premature birth, and postpartum hemorrhage (3,4,5). Conception in this group of patients usually requires the support of assisted reproductive techniques. Induction of ovulation by means of human or recombinant gonadotrophins is widely used in current practice. Progestrogen support following conception, optimizing other hormonal replacement and careful monitoring throughout pregnancy play a vital role in successful pregnancy outcomes. We report a subject with panhypopituitarism who was managed in our Endocrine Antenatal clinic with successful outcome.

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Irreversible damage to auditory system functions caused by perinatal hypothyroidism in rats

Cited by 9 publications

References 28 publications

Acoustic alterations of ultrasonic vocalization in rat pups induced by perinatal hypothyroidism

Acoustic alterations of ultrasonic vocalization in rat pups induced by perinatal hypothyroidism

In Utero and Postnatal Propylthiouracil-Induced Mild Hypothyroidism Impairs Maternal Behavior in Mice

Successful twin pregnancy in panhypopituitarism

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