{"title":"JJH201501 对大鼠的生殖毒性：围产期研究","authors":"Menghan Sun, Peng Yue, Hongqun Qiao","doi":"10.1002/bdr2.2303","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Introduction</h3>\n \n <p>In this study, JJH201501 was examined for reproductive toxicity during the perinatal period to support its safety as a novel serotonergic agent (5-HT) antidepressant. Pregnant Sprague–Dawley rats (F0, <i>n</i> = 24/group) were continuously exposed to 0 (control), 6, 18, and 60 mg/kg body weight/day of JJH201501 by intragastric administration from gestation day 15 to lactation day 21.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>During this period, maternal toxicity was evaluated based on clinical signs, body weight, feed intake, delivery condition, litter parameters, and necropsy, with body weight, sex ratios, malformation incidence, physical, and neurodevelopmental assessments conducted on all offspring rats. Ten pups (male:female 1:1) from each dam within each dose group on postnatal day 4 (PND4) were randomly selected. One pair was evaluated for behavior evaluations (F1a) after PND35, one for reproduction performance (F1b) after 10 weeks, and three for organ weight and deformities (F1c) on PND35. After successful mating, F1b male rats were weighed and dissected to assess reproductive organ weight and sperm motility. Pregnant F1b rats were weighed and monitored for food intake twice weekly until laparotomy on GD14, which recorded live/dead fetuses, resorptions, implantations, corpora lutea, and uterine weight. Some statistical differences were found between the JJH-treated and control groups in maternal weight, food consumption, and F1 body weight and water maze performance.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Autopsy results showed that JJH201501 had a low cardiac index effect in F0, with no significant histopathological changes detected. Only one F1 offspring died in the high-dose group throughout the experiment. Due to the lack of dose-dependent effects and the consistent growth pattern of these alterations, the study findings do not suggest any toxicological significance for the observed results.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>In conclusion, the no-observed-adverse-effect level of JJH201501 for perinatal rats is about 60 mg/kg b.w./day.</p>\n </section>\n </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":null,"pages":null},"PeriodicalIF":1.6000,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Reproductive toxicity of JJH201501 in rats: Perinatal study\",\"authors\":\"Menghan Sun, Peng Yue, Hongqun Qiao\",\"doi\":\"10.1002/bdr2.2303\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Introduction</h3>\\n \\n <p>In this study, JJH201501 was examined for reproductive toxicity during the perinatal period to support its safety as a novel serotonergic agent (5-HT) antidepressant. Pregnant Sprague–Dawley rats (F0, <i>n</i> = 24/group) were continuously exposed to 0 (control), 6, 18, and 60 mg/kg body weight/day of JJH201501 by intragastric administration from gestation day 15 to lactation day 21.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>During this period, maternal toxicity was evaluated based on clinical signs, body weight, feed intake, delivery condition, litter parameters, and necropsy, with body weight, sex ratios, malformation incidence, physical, and neurodevelopmental assessments conducted on all offspring rats. Ten pups (male:female 1:1) from each dam within each dose group on postnatal day 4 (PND4) were randomly selected. One pair was evaluated for behavior evaluations (F1a) after PND35, one for reproduction performance (F1b) after 10 weeks, and three for organ weight and deformities (F1c) on PND35. After successful mating, F1b male rats were weighed and dissected to assess reproductive organ weight and sperm motility. Pregnant F1b rats were weighed and monitored for food intake twice weekly until laparotomy on GD14, which recorded live/dead fetuses, resorptions, implantations, corpora lutea, and uterine weight. Some statistical differences were found between the JJH-treated and control groups in maternal weight, food consumption, and F1 body weight and water maze performance.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Autopsy results showed that JJH201501 had a low cardiac index effect in F0, with no significant histopathological changes detected. Only one F1 offspring died in the high-dose group throughout the experiment. Due to the lack of dose-dependent effects and the consistent growth pattern of these alterations, the study findings do not suggest any toxicological significance for the observed results.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>In conclusion, the no-observed-adverse-effect level of JJH201501 for perinatal rats is about 60 mg/kg b.w./day.</p>\\n </section>\\n </div>\",\"PeriodicalId\":9121,\"journal\":{\"name\":\"Birth Defects Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2024-01-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Birth Defects Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/bdr2.2303\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"DEVELOPMENTAL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Birth Defects Research","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/bdr2.2303","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"DEVELOPMENTAL BIOLOGY","Score":null,"Total":0}
Reproductive toxicity of JJH201501 in rats: Perinatal study
Introduction
In this study, JJH201501 was examined for reproductive toxicity during the perinatal period to support its safety as a novel serotonergic agent (5-HT) antidepressant. Pregnant Sprague–Dawley rats (F0, n = 24/group) were continuously exposed to 0 (control), 6, 18, and 60 mg/kg body weight/day of JJH201501 by intragastric administration from gestation day 15 to lactation day 21.
Methods
During this period, maternal toxicity was evaluated based on clinical signs, body weight, feed intake, delivery condition, litter parameters, and necropsy, with body weight, sex ratios, malformation incidence, physical, and neurodevelopmental assessments conducted on all offspring rats. Ten pups (male:female 1:1) from each dam within each dose group on postnatal day 4 (PND4) were randomly selected. One pair was evaluated for behavior evaluations (F1a) after PND35, one for reproduction performance (F1b) after 10 weeks, and three for organ weight and deformities (F1c) on PND35. After successful mating, F1b male rats were weighed and dissected to assess reproductive organ weight and sperm motility. Pregnant F1b rats were weighed and monitored for food intake twice weekly until laparotomy on GD14, which recorded live/dead fetuses, resorptions, implantations, corpora lutea, and uterine weight. Some statistical differences were found between the JJH-treated and control groups in maternal weight, food consumption, and F1 body weight and water maze performance.
Results
Autopsy results showed that JJH201501 had a low cardiac index effect in F0, with no significant histopathological changes detected. Only one F1 offspring died in the high-dose group throughout the experiment. Due to the lack of dose-dependent effects and the consistent growth pattern of these alterations, the study findings do not suggest any toxicological significance for the observed results.
Conclusion
In conclusion, the no-observed-adverse-effect level of JJH201501 for perinatal rats is about 60 mg/kg b.w./day.
期刊介绍：
The journal Birth Defects Research publishes original research and reviews in areas related to the etiology of adverse developmental and reproductive outcome. In particular the journal is devoted to the publication of original scientific research that contributes to the understanding of the biology of embryonic development and the prenatal causative factors and mechanisms leading to adverse pregnancy outcomes, namely structural and functional birth defects, pregnancy loss, postnatal functional defects in the human population, and to the identification of prenatal factors and biological mechanisms that reduce these risks.
Adverse reproductive and developmental outcomes may have genetic, environmental, nutritional or epigenetic causes. Accordingly, the journal Birth Defects Research takes an integrated, multidisciplinary approach in its organization and publication strategy. The journal Birth Defects Research contains separate sections for clinical and molecular teratology, developmental and reproductive toxicology, and reviews in developmental biology to acknowledge and accommodate the integrative nature of research in this field. Each section has a dedicated editor who is a leader in his/her field and who has full editorial authority in his/her area.
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