Mohamed Ali Alabiad, Ibtesam Elhasadi, Sulaiman Mohammed Alnasser, Mohammed Alorini, Ahmed Baker A Alshaikh, Fatima A Jaber, Amany Mohamed Shalaby, Walaa Samy, Ahmed Ismail Heraiz, Khalid Mohammed Mohammed Albakoush, Dina Ahmed Khairy
{"title":"芳香化酶抑制剂来曲唑对成年白化大鼠胎盘的影响:组织病理学、免疫组织化学和生物化学研究。","authors":"Mohamed Ali Alabiad, Ibtesam Elhasadi, Sulaiman Mohammed Alnasser, Mohammed Alorini, Ahmed Baker A Alshaikh, Fatima A Jaber, Amany Mohamed Shalaby, Walaa Samy, Ahmed Ismail Heraiz, Khalid Mohammed Mohammed Albakoush, Dina Ahmed Khairy","doi":"10.30476/IJMS.2023.96905.2853","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Letrozole, an aromatase inhibitor, has recently been introduced as the preferred treatment option for ectopic pregnancy. To date, no study has investigated the effect of letrozole alone on placental tissue. The present study aimed to evaluate the effect of different doses of letrozole on the placenta of rats and to clarify the underlying mechanism.</p><p><strong>Methods: </strong>Sixty pregnant female rats were equally divided into three groups, namely the control group (GI), low-dose (0.5 mg/Kg/day) letrozole group (GII), which is equivalent to the human daily dose (HED) of 5 mg, and high-dose (1 mg/Kg/day) letrozole group (GIII), equivalent to the HED of 10 mg. Letrozole was administered by oral gavage daily from day 6 to 16 of gestation. Data were analyzed using a one-way analysis of variance followed by Tukey's <i>post hoc</i> test and Chi square test. P<0.05 was considered statistically significant.</p><p><strong>Results: </strong>Compared to the GI and GII groups, high-dose letrozole significantly increased embryonic mortality with a high post-implantation loss rate (P<0.001) and significantly reduced the number of viable fetuses (P<0.001) and placental weight (P<0.001) of pregnant rats. Moreover, it significantly reduced placental estrogen receptor (ER) and progesterone receptor (PR) (P<0.001) and the expression of vascular endothelial growth factor (P<0.001), while increasing the apoptotic index of cleaved caspase-3 (P<0.001).</p><p><strong>Conclusion: </strong>Letrozole inhibited the expression of ER and PR in rat placenta. It interrupted stimulatory vascular signals causing significant apoptosis and placental vascular dysfunction. Letrozole in an equivalent human daily dose of 10 mg caused a high post-implantation loss rate without imposing severe side effects.</p>","PeriodicalId":14510,"journal":{"name":"Iranian Journal of Medical Sciences","volume":"49 1","pages":"46-56"},"PeriodicalIF":1.6000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10839141/pdf/","citationCount":"0","resultStr":"{\"title\":\"Effect of Aromatase Inhibitor Letrozole on the Placenta of Adult Albino Rats: A Histopathological, Immunohistochemical, and Biochemical Study.\",\"authors\":\"Mohamed Ali Alabiad, Ibtesam Elhasadi, Sulaiman Mohammed Alnasser, Mohammed Alorini, Ahmed Baker A Alshaikh, Fatima A Jaber, Amany Mohamed Shalaby, Walaa Samy, Ahmed Ismail Heraiz, Khalid Mohammed Mohammed Albakoush, Dina Ahmed Khairy\",\"doi\":\"10.30476/IJMS.2023.96905.2853\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Letrozole, an aromatase inhibitor, has recently been introduced as the preferred treatment option for ectopic pregnancy. To date, no study has investigated the effect of letrozole alone on placental tissue. The present study aimed to evaluate the effect of different doses of letrozole on the placenta of rats and to clarify the underlying mechanism.</p><p><strong>Methods: </strong>Sixty pregnant female rats were equally divided into three groups, namely the control group (GI), low-dose (0.5 mg/Kg/day) letrozole group (GII), which is equivalent to the human daily dose (HED) of 5 mg, and high-dose (1 mg/Kg/day) letrozole group (GIII), equivalent to the HED of 10 mg. Letrozole was administered by oral gavage daily from day 6 to 16 of gestation. Data were analyzed using a one-way analysis of variance followed by Tukey's <i>post hoc</i> test and Chi square test. P<0.05 was considered statistically significant.</p><p><strong>Results: </strong>Compared to the GI and GII groups, high-dose letrozole significantly increased embryonic mortality with a high post-implantation loss rate (P<0.001) and significantly reduced the number of viable fetuses (P<0.001) and placental weight (P<0.001) of pregnant rats. Moreover, it significantly reduced placental estrogen receptor (ER) and progesterone receptor (PR) (P<0.001) and the expression of vascular endothelial growth factor (P<0.001), while increasing the apoptotic index of cleaved caspase-3 (P<0.001).</p><p><strong>Conclusion: </strong>Letrozole inhibited the expression of ER and PR in rat placenta. It interrupted stimulatory vascular signals causing significant apoptosis and placental vascular dysfunction. Letrozole in an equivalent human daily dose of 10 mg caused a high post-implantation loss rate without imposing severe side effects.</p>\",\"PeriodicalId\":14510,\"journal\":{\"name\":\"Iranian Journal of Medical Sciences\",\"volume\":\"49 1\",\"pages\":\"46-56\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10839141/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Iranian Journal of Medical Sciences\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.30476/IJMS.2023.96905.2853\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Iranian Journal of Medical Sciences","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.30476/IJMS.2023.96905.2853","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0
摘要
背景:来曲唑是一种芳香化酶抑制剂,最近已成为治疗异位妊娠的首选药物。迄今为止,还没有研究单独使用来曲唑对胎盘组织的影响。本研究旨在评估不同剂量的来曲唑对大鼠胎盘的影响,并阐明其潜在机制:将60只妊娠雌性大鼠平均分为三组,即对照组(GI)、低剂量(0.5 mg/Kg/天)来曲唑组(GII)(相当于人类日剂量(HED)5 mg)和高剂量(1 mg/Kg/天)来曲唑组(GIII)(相当于HED 10 mg)。来曲唑在妊娠期第6至16天每天口服给药。数据采用单因素方差分析,然后进行Tukey's事后检验和Chi square检验。结果与GI组和GII组相比,高剂量来曲唑显著增加了胚胎死亡率,且胚胎植入后丢失率较高:来曲唑抑制了大鼠胎盘中 ER 和 PR 的表达。来曲唑可抑制大鼠胎盘中 ER 和 PR 的表达,中断血管刺激信号,导致大量细胞凋亡和胎盘血管功能障碍。来曲唑在人体中的等效日剂量为 10 毫克,在不产生严重副作用的情况下,会导致较高的胚胎着床后丢失率。
Effect of Aromatase Inhibitor Letrozole on the Placenta of Adult Albino Rats: A Histopathological, Immunohistochemical, and Biochemical Study.
Background: Letrozole, an aromatase inhibitor, has recently been introduced as the preferred treatment option for ectopic pregnancy. To date, no study has investigated the effect of letrozole alone on placental tissue. The present study aimed to evaluate the effect of different doses of letrozole on the placenta of rats and to clarify the underlying mechanism.
Methods: Sixty pregnant female rats were equally divided into three groups, namely the control group (GI), low-dose (0.5 mg/Kg/day) letrozole group (GII), which is equivalent to the human daily dose (HED) of 5 mg, and high-dose (1 mg/Kg/day) letrozole group (GIII), equivalent to the HED of 10 mg. Letrozole was administered by oral gavage daily from day 6 to 16 of gestation. Data were analyzed using a one-way analysis of variance followed by Tukey's post hoc test and Chi square test. P<0.05 was considered statistically significant.
Results: Compared to the GI and GII groups, high-dose letrozole significantly increased embryonic mortality with a high post-implantation loss rate (P<0.001) and significantly reduced the number of viable fetuses (P<0.001) and placental weight (P<0.001) of pregnant rats. Moreover, it significantly reduced placental estrogen receptor (ER) and progesterone receptor (PR) (P<0.001) and the expression of vascular endothelial growth factor (P<0.001), while increasing the apoptotic index of cleaved caspase-3 (P<0.001).
Conclusion: Letrozole inhibited the expression of ER and PR in rat placenta. It interrupted stimulatory vascular signals causing significant apoptosis and placental vascular dysfunction. Letrozole in an equivalent human daily dose of 10 mg caused a high post-implantation loss rate without imposing severe side effects.
期刊介绍:
The Iranian Journal of Medical Sciences (IJMS) is an international quarterly biomedical publication, which is sponsored by Shiraz University of Medical Sciences. The IJMS intends to provide a scientific medium of communication for researchers throughout the globe. The journal welcomes original clinical articles as well as clinically oriented basic science research experiences on prevalent diseases in the region and analysis of various regional problems.