Repercussões do hipotireoidismo gestacional e perinatal experimental na função auditiva da prole de ratas

Detalhes bibliográficos
Autor(a) principal: Oliveira, Priscila Feliciano de
Data de Publicação: 2018
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da UFS
Texto Completo: http://ri.ufs.br/jspui/handle/riufs/7481
Resumo: Introduction: Thyroid hormones (TH) during gestation are critical for fetal growth and development of hearing organ. The lack of maternal TH leads an inadequate development of Organ of Corti with malformation of internal sulcus, tectorial membrane, cochlear ductus and a hair cells differentiation. It can adversely affect the auditory system, which can cause a hearing loss. Experimental studies are performed with postnatal period hypothyroidism induction, but there are no investigations that induce at gestational period. The impact of thyroid hypofunction restricted to the embryonic period remains unknown, which makes this study unpublished. Objective: To evaluate the effect of gestational hypothyroidism on auditory function of adult offspring in rats. Methods: The research was composed by Wistar rats and it was approved by the Ethics Committee on Animal Research of Federal University of Sergipe (Protocol #21/15). Pregnant Wistar rats were given the antithyroid drug methimazole (0.02% - 1-methylimidazole-2-thiol – MMI, in drinking water, ad libitum) from gestational day (GD) 9 to delivery day (GD 21-22), and comprises a offspring from gestational MMI-treated dams group (OGMTD). To lactation hypothyroidism group [offspring from perinatal MMI-treated dams group (OPMTD)] the drug was given from 9ºGD to the 15th postnatal day (PND). Part of the OGMTD and OPMTD groups received replacement of HT with levothyroxine at the concentration of 50 μg / 100 mL in drinking water. All animals were evaluated by tympanometry, distortion product otoacoustic emission (DPOAE) and auditory evoked brainstem response (ABR) at 30, 60, 90 and 120 PND. Results: Our data demonstrated no middle ear dysfunction; regardless of hypothyroidism groups, compliance was lower than the control group (p<0,005). DPOAE was lower in OGMTD from 4 up to 12 kilohertz (kHz) and absent in OPMTD (p<0,001). On the other hand, ABR revealed normal integrity of neural auditory pathways up to brainstem level in the central nervous system, with no latency modification. Additionally, hypothyroidism groups presented a higher electrophysiological threshold (i.e., hearing loss), worse repercussion in OPMTD (p<0,001). Groups treated with levothyroxine did not reveal difference on hearing behavior compared to hypothyroidism groups. Our data suggest that gestational hypothyroidism leads to a cochlear damage function in offspring, with normality of the auditory pathways to the brainsten with moderate to profound sensorineural hearing loss.
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spelling Oliveira, Priscila Feliciano dePassos Junior, Daniel Badauê2018-03-06T19:11:45Z2018-03-06T19:11:45Z2018-02-02OLIVEIRA, Priscila Feliciano de. Repercussões do hipotireoidismo gestacional e perinatal experimental na função auditiva da prole de ratas. 2018. 102 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Sergipe, Aracaju, SE, 2018.http://ri.ufs.br/jspui/handle/riufs/7481Introduction: Thyroid hormones (TH) during gestation are critical for fetal growth and development of hearing organ. The lack of maternal TH leads an inadequate development of Organ of Corti with malformation of internal sulcus, tectorial membrane, cochlear ductus and a hair cells differentiation. It can adversely affect the auditory system, which can cause a hearing loss. Experimental studies are performed with postnatal period hypothyroidism induction, but there are no investigations that induce at gestational period. The impact of thyroid hypofunction restricted to the embryonic period remains unknown, which makes this study unpublished. Objective: To evaluate the effect of gestational hypothyroidism on auditory function of adult offspring in rats. Methods: The research was composed by Wistar rats and it was approved by the Ethics Committee on Animal Research of Federal University of Sergipe (Protocol #21/15). Pregnant Wistar rats were given the antithyroid drug methimazole (0.02% - 1-methylimidazole-2-thiol – MMI, in drinking water, ad libitum) from gestational day (GD) 9 to delivery day (GD 21-22), and comprises a offspring from gestational MMI-treated dams group (OGMTD). To lactation hypothyroidism group [offspring from perinatal MMI-treated dams group (OPMTD)] the drug was given from 9ºGD to the 15th postnatal day (PND). Part of the OGMTD and OPMTD groups received replacement of HT with levothyroxine at the concentration of 50 μg / 100 mL in drinking water. All animals were evaluated by tympanometry, distortion product otoacoustic emission (DPOAE) and auditory evoked brainstem response (ABR) at 30, 60, 90 and 120 PND. Results: Our data demonstrated no middle ear dysfunction; regardless of hypothyroidism groups, compliance was lower than the control group (p<0,005). DPOAE was lower in OGMTD from 4 up to 12 kilohertz (kHz) and absent in OPMTD (p<0,001). On the other hand, ABR revealed normal integrity of neural auditory pathways up to brainstem level in the central nervous system, with no latency modification. Additionally, hypothyroidism groups presented a higher electrophysiological threshold (i.e., hearing loss), worse repercussion in OPMTD (p<0,001). Groups treated with levothyroxine did not reveal difference on hearing behavior compared to hypothyroidism groups. Our data suggest that gestational hypothyroidism leads to a cochlear damage function in offspring, with normality of the auditory pathways to the brainsten with moderate to profound sensorineural hearing loss.Introdução: Os hormônios tireoidianos (HT) durante a gestação são críticos para o desenvolvimento do órgão da audição. A hipofunção da tireoide neste período provoca má formação do órgão de Corti, caracterizada por alteração no sulco interno, membrana tectorial, ducto colcear, além de dificuldade na diferenciação das células ciliadas. Estas alterações repercutem negativamente no sistema auditivo, que pode culminar em perda auditiva. Estudos experimentais são realizados com a indução do hipotireoidismo até o período pós-natal, porém não há pesquisas que induzam apenas no período gestacional. O impacto da hipofunção tireoidiana restrita ao período embrionário permanece desconhecida, o que torna este estudo inédito.Objetivo: Avaliar o efeito do hipotireoidismo gestacional experimental na função auditiva da prole adulta em ratos. Material e Método: A pesquisa foi realizada com ratos Wistar e foi aprovada pelo Comite de ética em pesquisa com animais da UFS, sob o número 21/2015. Foi administrado às ratas Wistar prenhes o fármaco antitireoidiano metimazol (0,02% - 1-metilimidazol-2-tiol, em água potável, ad libitum.) do nono dia gestacional (DG) até o dia do parto (21-22DG), e formaram o grupo da prole de mães induzidas ao hipotireodismo gestacional (PMHG). No grupo até a lactação [prole de mães induzidas ao hipotireodismo perinatal (PMHPN)], o fármaco metimazol foi administrado do 9ºDG ao 15º dia pós natal (DPN). Parte dos grupos PMHG e PMHPN receberam reposição dos HT com Levotiroxina na concentração de 50 μg/100 mL na água de beber. Todos os animais foram submetidos aos seguintes procedimentos: exames de timpanometria, emissão otoacústica por produto de distorção (EOAPD) e potencial evocado auditivo de tronco encefálico (PEATE) nas idades de 30, 60, 90 e 120 DPN. Resultados: Os dados não demonstraram disfunção da orelha média; porém os grupos induzidos ao hipotireidismo apresentaram menores valores de compliância que o grupo prole de mães eutiroidianas (p<0,05). EOAPD foi menor no PMHG de 4 a 12 kilohertz (kHz), com ausência de respostas no PMHPN (p<0,001). Por outro lado, o PEATE revelou integridade das vias auditivas neurais até o nível do tronco encefálico no sistema nervoso central, sem modificação de latência. Além disso, os grupos com hipofunção tireoidiana apresentaram maiores limiares eletrofisiológicos (isto é, perda auditiva), com pior repercussão no grupo PMHPN (p<0,001). Não foi observada reversão da hipofunção tireoidiana nos grupos que receberam o reposição dos HT, uma vez que apresentaram o mesmo comportamento auditivo funcional que os grupos sem o tratamento com levotiroxina. Conclusão: O hipotireoidismo gestacional altera a função coclear da prole, com normalidade da integridade das vias auditivas até tronco encefálico e presença de perda auditiva sensório neural de grau moderado a profundo.Aracaju, SEporHipotireoidismoHipotireoidismo congênitoCócleaPerda auditivaRatosHypothyroidismCongenital hypothyroidismCochleaHearing lossRatsCIENCIAS DA SAUDERepercussões do hipotireoidismo gestacional e perinatal experimental na função auditiva da prole de ratasRepercussions of gestational and perinatal experimental hypotioidism in hearing function of offspring ratinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisPós-Graduação em Ciências da SaúdeUniversidade Federal de Sergipereponame:Repositório Institucional da UFSinstname:Universidade Federal de Sergipe (UFS)instacron:UFSinfo:eu-repo/semantics/openAccessLICENSElicense.txtlicense.txttext/plain; charset=utf-81475https://ri.ufs.br/jspui/bitstream/riufs/7481/1/license.txt098cbbf65c2c15e1fb2e49c5d306a44cMD51ORIGINALPRISCILA_FELICIANO_OLIVEIRA.pdfPRISCILA_FELICIANO_OLIVEIRA.pdfapplication/pdf2301619https://ri.ufs.br/jspui/bitstream/riufs/7481/2/PRISCILA_FELICIANO_OLIVEIRA.pdfa3394504fea5b0d886dacb974b95e272MD52TEXTPRISCILA_FELICIANO_OLIVEIRA.pdf.txtPRISCILA_FELICIANO_OLIVEIRA.pdf.txtExtracted texttext/plain218120https://ri.ufs.br/jspui/bitstream/riufs/7481/3/PRISCILA_FELICIANO_OLIVEIRA.pdf.txt6a0757c12e7d661ea698c3db9f29e304MD53THUMBNAILPRISCILA_FELICIANO_OLIVEIRA.pdf.jpgPRISCILA_FELICIANO_OLIVEIRA.pdf.jpgGenerated Thumbnailimage/jpeg1289https://ri.ufs.br/jspui/bitstream/riufs/7481/4/PRISCILA_FELICIANO_OLIVEIRA.pdf.jpg3d5c6388cff62db58a6e11ab5baac53dMD54riufs/74812018-03-06 16:11:46.007oai:ufs.br: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Repositório InstitucionalPUBhttps://ri.ufs.br/oai/requestrepositorio@academico.ufs.bropendoar:2018-03-06T19:11:46Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS)false
dc.title.pt_BR.fl_str_mv Repercussões do hipotireoidismo gestacional e perinatal experimental na função auditiva da prole de ratas
dc.title.alternative.eng.fl_str_mv Repercussions of gestational and perinatal experimental hypotioidism in hearing function of offspring rat
title Repercussões do hipotireoidismo gestacional e perinatal experimental na função auditiva da prole de ratas
spellingShingle Repercussões do hipotireoidismo gestacional e perinatal experimental na função auditiva da prole de ratas
Oliveira, Priscila Feliciano de
Hipotireoidismo
Hipotireoidismo congênito
Cóclea
Perda auditiva
Ratos
Hypothyroidism
Congenital hypothyroidism
Cochlea
Hearing loss
Rats
CIENCIAS DA SAUDE
title_short Repercussões do hipotireoidismo gestacional e perinatal experimental na função auditiva da prole de ratas
title_full Repercussões do hipotireoidismo gestacional e perinatal experimental na função auditiva da prole de ratas
title_fullStr Repercussões do hipotireoidismo gestacional e perinatal experimental na função auditiva da prole de ratas
title_full_unstemmed Repercussões do hipotireoidismo gestacional e perinatal experimental na função auditiva da prole de ratas
title_sort Repercussões do hipotireoidismo gestacional e perinatal experimental na função auditiva da prole de ratas
author Oliveira, Priscila Feliciano de
author_facet Oliveira, Priscila Feliciano de
author_role author
dc.contributor.author.fl_str_mv Oliveira, Priscila Feliciano de
dc.contributor.advisor1.fl_str_mv Passos Junior, Daniel Badauê
contributor_str_mv Passos Junior, Daniel Badauê
dc.subject.por.fl_str_mv Hipotireoidismo
Hipotireoidismo congênito
Cóclea
Perda auditiva
Ratos
topic Hipotireoidismo
Hipotireoidismo congênito
Cóclea
Perda auditiva
Ratos
Hypothyroidism
Congenital hypothyroidism
Cochlea
Hearing loss
Rats
CIENCIAS DA SAUDE
dc.subject.eng.fl_str_mv Hypothyroidism
Congenital hypothyroidism
Cochlea
Hearing loss
Rats
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE
description Introduction: Thyroid hormones (TH) during gestation are critical for fetal growth and development of hearing organ. The lack of maternal TH leads an inadequate development of Organ of Corti with malformation of internal sulcus, tectorial membrane, cochlear ductus and a hair cells differentiation. It can adversely affect the auditory system, which can cause a hearing loss. Experimental studies are performed with postnatal period hypothyroidism induction, but there are no investigations that induce at gestational period. The impact of thyroid hypofunction restricted to the embryonic period remains unknown, which makes this study unpublished. Objective: To evaluate the effect of gestational hypothyroidism on auditory function of adult offspring in rats. Methods: The research was composed by Wistar rats and it was approved by the Ethics Committee on Animal Research of Federal University of Sergipe (Protocol #21/15). Pregnant Wistar rats were given the antithyroid drug methimazole (0.02% - 1-methylimidazole-2-thiol – MMI, in drinking water, ad libitum) from gestational day (GD) 9 to delivery day (GD 21-22), and comprises a offspring from gestational MMI-treated dams group (OGMTD). To lactation hypothyroidism group [offspring from perinatal MMI-treated dams group (OPMTD)] the drug was given from 9ºGD to the 15th postnatal day (PND). Part of the OGMTD and OPMTD groups received replacement of HT with levothyroxine at the concentration of 50 μg / 100 mL in drinking water. All animals were evaluated by tympanometry, distortion product otoacoustic emission (DPOAE) and auditory evoked brainstem response (ABR) at 30, 60, 90 and 120 PND. Results: Our data demonstrated no middle ear dysfunction; regardless of hypothyroidism groups, compliance was lower than the control group (p<0,005). DPOAE was lower in OGMTD from 4 up to 12 kilohertz (kHz) and absent in OPMTD (p<0,001). On the other hand, ABR revealed normal integrity of neural auditory pathways up to brainstem level in the central nervous system, with no latency modification. Additionally, hypothyroidism groups presented a higher electrophysiological threshold (i.e., hearing loss), worse repercussion in OPMTD (p<0,001). Groups treated with levothyroxine did not reveal difference on hearing behavior compared to hypothyroidism groups. Our data suggest that gestational hypothyroidism leads to a cochlear damage function in offspring, with normality of the auditory pathways to the brainsten with moderate to profound sensorineural hearing loss.
publishDate 2018
dc.date.accessioned.fl_str_mv 2018-03-06T19:11:45Z
dc.date.available.fl_str_mv 2018-03-06T19:11:45Z
dc.date.issued.fl_str_mv 2018-02-02
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dc.identifier.citation.fl_str_mv OLIVEIRA, Priscila Feliciano de. Repercussões do hipotireoidismo gestacional e perinatal experimental na função auditiva da prole de ratas. 2018. 102 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Sergipe, Aracaju, SE, 2018.
dc.identifier.uri.fl_str_mv http://ri.ufs.br/jspui/handle/riufs/7481
identifier_str_mv OLIVEIRA, Priscila Feliciano de. Repercussões do hipotireoidismo gestacional e perinatal experimental na função auditiva da prole de ratas. 2018. 102 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Sergipe, Aracaju, SE, 2018.
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