{"title":"[化学物质引起的围产期甲状腺激素紊乱和大脑发育逆境:旨在开发新的评估方法的努力现状]。","authors":"Tomoya Yamada","doi":"10.1254/fpj.24058","DOIUrl":null,"url":null,"abstract":"<p><p>Fetal thyroid hormones (THs), essential for brain development, largely depend on maternal supply. Clinical studies have shown that TH alterations in pregnant mothers can lead to permanent neurodevelopmental effects in their children, suggesting that chemicals causing maternal TH disruption may require regulation. However, the quantitative relationship between chemical-induced maternal TH reductions and fetal brain TH disruption, as well as fetal brain developmental abnormalities, is not fully understood. Thus, there is a need for methods that can precisely, rapidly, and quantitatively evaluate TH-disrupting effects of test chemicals that may cause brain abnormalities. Currently, multiple molecular initiating events (MIEs) in the adverse outcome pathways (AOPs) of TH disruption are known, and tests using New Approach Methodologies are being developed to investigate the effects of chemicals on these MIEs. Additionally, the Comparative Thyroid Assay (CTA) is expected to be utilized to comparatively evaluate the decrease in blood TH concentrations, commonly observed as a result of actions on multiple MIEs, in maternal rats along with their offspring. Recently, due to the increasing need for more precise and efficient evaluations and the reduction of animal testing, we have worked on improving the CTA. We proposed a modified CTA that adds new test items: brain TH concentrations and heterotopia (a histological marker of brain TH deficiency), while reducing the number of animals used by 50%. Feasibility studies confirmed that it can detect approximately 20-30% TH disruption in the offspring brain. This review outlines the current efforts to develop new evaluation methods for perinatal TH disruption effects.</p>","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 2","pages":"108-114"},"PeriodicalIF":0.0000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"[Chemical-induced perinatal thyroid hormone disruption and brain developmental adversity: status of efforts aimed at developing new evaluation methods].\",\"authors\":\"Tomoya Yamada\",\"doi\":\"10.1254/fpj.24058\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Fetal thyroid hormones (THs), essential for brain development, largely depend on maternal supply. Clinical studies have shown that TH alterations in pregnant mothers can lead to permanent neurodevelopmental effects in their children, suggesting that chemicals causing maternal TH disruption may require regulation. However, the quantitative relationship between chemical-induced maternal TH reductions and fetal brain TH disruption, as well as fetal brain developmental abnormalities, is not fully understood. Thus, there is a need for methods that can precisely, rapidly, and quantitatively evaluate TH-disrupting effects of test chemicals that may cause brain abnormalities. Currently, multiple molecular initiating events (MIEs) in the adverse outcome pathways (AOPs) of TH disruption are known, and tests using New Approach Methodologies are being developed to investigate the effects of chemicals on these MIEs. Additionally, the Comparative Thyroid Assay (CTA) is expected to be utilized to comparatively evaluate the decrease in blood TH concentrations, commonly observed as a result of actions on multiple MIEs, in maternal rats along with their offspring. Recently, due to the increasing need for more precise and efficient evaluations and the reduction of animal testing, we have worked on improving the CTA. We proposed a modified CTA that adds new test items: brain TH concentrations and heterotopia (a histological marker of brain TH deficiency), while reducing the number of animals used by 50%. Feasibility studies confirmed that it can detect approximately 20-30% TH disruption in the offspring brain. This review outlines the current efforts to develop new evaluation methods for perinatal TH disruption effects.</p>\",\"PeriodicalId\":12208,\"journal\":{\"name\":\"Folia Pharmacologica Japonica\",\"volume\":\"160 2\",\"pages\":\"108-114\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Folia Pharmacologica Japonica\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1254/fpj.24058\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Folia Pharmacologica Japonica","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1254/fpj.24058","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
[Chemical-induced perinatal thyroid hormone disruption and brain developmental adversity: status of efforts aimed at developing new evaluation methods].
Fetal thyroid hormones (THs), essential for brain development, largely depend on maternal supply. Clinical studies have shown that TH alterations in pregnant mothers can lead to permanent neurodevelopmental effects in their children, suggesting that chemicals causing maternal TH disruption may require regulation. However, the quantitative relationship between chemical-induced maternal TH reductions and fetal brain TH disruption, as well as fetal brain developmental abnormalities, is not fully understood. Thus, there is a need for methods that can precisely, rapidly, and quantitatively evaluate TH-disrupting effects of test chemicals that may cause brain abnormalities. Currently, multiple molecular initiating events (MIEs) in the adverse outcome pathways (AOPs) of TH disruption are known, and tests using New Approach Methodologies are being developed to investigate the effects of chemicals on these MIEs. Additionally, the Comparative Thyroid Assay (CTA) is expected to be utilized to comparatively evaluate the decrease in blood TH concentrations, commonly observed as a result of actions on multiple MIEs, in maternal rats along with their offspring. Recently, due to the increasing need for more precise and efficient evaluations and the reduction of animal testing, we have worked on improving the CTA. We proposed a modified CTA that adds new test items: brain TH concentrations and heterotopia (a histological marker of brain TH deficiency), while reducing the number of animals used by 50%. Feasibility studies confirmed that it can detect approximately 20-30% TH disruption in the offspring brain. This review outlines the current efforts to develop new evaluation methods for perinatal TH disruption effects.