亲代丙硫氧嘧啶暴露对子代的影响
Effects of Parental Propylthiouracil Exposure on Offspring
DOI: 10.12677/acm.2025.15102813, PDF,   
作者: 倪诗景, 杨 方, 谌崇峰：暨南大学附属第一医院儿科，广东 广州
关键词: 丙硫氧嘧啶；妊娠；子代；甲状腺功能；发育；Propylthiouracil； Pregnancy； Offspring； Thyroid Function； Development
摘要: 丙硫氧嘧啶(PTU)作为治疗甲状腺功能亢进症(甲亢)的常用药物，其在妊娠期应用的安全性及对子代的潜在影响备受关注。本文综合现有临床研究及动物实验证据，探讨亲代(尤其是母体) PTU暴露对子代健康产生的短期及长期影响，以便为临床医生全面了解丙硫氧嘧啶与子代健康之间的关联提供参考，从而减少临床上亲代丙硫氧嘧啶暴露对子代的影响。
Abstract: Propylthiouracil (PTU) is a commonly used drug for treating hyperthyroidism. The safety of its application during pregnancy and its potential impact on offspring have drawn considerable attention. This article comprehensively reviews existing clinical research and animal experimental evidence to explore the short-term and long-term effects of parental (especially maternal) PTU exposure on offspring health. The aim is to provide a reference for clinicians to fully understand the association between propylthiouracil and offspring health, thereby reducing the impact of parental PTU exposure on offspring in clinical practice.
文章引用：倪诗景, 杨方, 谌崇峰. 亲代丙硫氧嘧啶暴露对子代的影响[J]. 临床医学进展, 2025, 15(10): 738-743. https://doi.org/10.12677/acm.2025.15102813

参考文献

[1] François Xavier, K.N., Patrick Brice, D.D., Modeste, W., Esther, N., Albert, K., Pierre, K., et al. (2019) Preventive Effects of Aframomum melegueta Extracts on the Reproductive Complications of Propylthiouracil‐Induced Hypothyroidism in Male Rat. Andrologia, 51, e13306. [Google Scholar] [CrossRef] [PubMed]
[2] 孟宇豪, 江晓翠, 萧闵, 等. 丙硫氧嘧啶通过内质网应激损害大鼠生精功能和精子质量的机制及疏肝补肾毓麟汤的干预作用[J]. 中国实验方剂学杂志, 2025, 31(9): 79-89.
[3] Lara, N.L.M., Silva Jr., V.A., Chiarini-Garcia, H., Garcia, S.K., Debeljuk, L., Hess, R.A., et al. (2020) Hypothyroidism Induced by Postnatal PTU (6-N-Propyl-2-Thiouracil) Treatment Decreases Sertoli Cell Number and Spermatogenic Efficiency in Sexually Mature Pigs. General and Comparative Endocrinology, 299, Article ID: 113593. [Google Scholar] [CrossRef] [PubMed]
[4] Figueiredo, A.F.A., Wnuk, N.T., Tavares, A.O., Miranda, J.R., Hess, R.A., de França, L.R., et al. (2019) Prepubertal PTU Treatment in Rat Increases Sertoli Cell Number and Sperm Production. Reproduction, 158, 201-211. [Google Scholar] [CrossRef] [PubMed]
[5] Andersen, S.L., Lönn, S., Vestergaard, P. and Törring, O. (2017) Birth Defects after Use of Antithyroid Drugs in Early Pregnancy: A Swedish Nationwide Study. European Journal of Endocrinology, 177, 369-378. [Google Scholar] [CrossRef] [PubMed]
[6] Morales, D.R., Fonkwen, L. and Nordeng, H.M.E. (2021) Antithyroid Drug Use during Pregnancy and the Risk of Birth Defects in Offspring: Systematic Review and Meta‐Analysis of Observational Studies with Methodological Considerations. British Journal of Clinical Pharmacology, 87, 3890-3900. [Google Scholar] [CrossRef] [PubMed]
[7] 赵琦. 丙基硫氧嘧啶治疗妊娠期甲亢的有效性和安全性分析[J]. 中国医药指南, 2018, 16(4): 126-127.
[8] 魏巧, 何金, 聂立红, 等. PTU和MMI对妊娠并甲状腺功能亢进患者肝脏负担及新生儿结局的影响[J]. 吉林医学, 2020, 41(10): 2395-2396.
[9] Gianetti, E., Russo, L., Orlandi, F., Chiovato, L., Giusti, M., Benvenga, S., et al. (2015) Pregnancy Outcome in Women Treated with Methimazole or Propylthiouracil during Pregnancy. Journal of Endocrinological Investigation, 38, 977-985. [Google Scholar] [CrossRef] [PubMed]
[10] 刘雅楠, 肖笛. 1例妊娠期丙硫氧嘧啶暴露致胎儿宫内甲状腺肿的治疗分析[J]. 医药导报, 2024, 43(3): 464-467.
[11] Axelstad, M., Hansen, P.R., Boberg, J., Bonnichsen, M., Nellemann, C., Lund, S.P., et al. (2008) Developmental Neurotoxicity of Propylthiouracil (PTU) in Rats: Relationship between Transient Hypothyroxinemia during Development and Long-Lasting Behavioural and Functional Changes. Toxicology and Applied Pharmacology, 232, 1-13. [Google Scholar] [CrossRef] [PubMed]
[12] Momotani, N., Yamashita, R., Makino, F., Noh, J.Y., Ishikawa, N., Ito, K., et al. (2000) Thyroid Function in Wholly Breast‐Feeding Infants Whose Mothers Take High Doses of Propylthiouracil. Clinical Endocrinology, 53, 177-181. [Google Scholar] [CrossRef] [PubMed]
[13] Ramhøj, L., Svingen, T., Frädrich, C., Rijntjes, E., Wirth, E.K., Pedersen, K., et al. (2022) Perinatal Exposure to the Thyroperoxidase Inhibitors Methimazole and Amitrole Perturbs Thyroid Hormone System Signaling and Alters Motor Activity in Rat Offspring. Toxicology Letters, 354, 44-55. [Google Scholar] [CrossRef] [PubMed]
[14] Khairinisa, M.A., Takatsuru, Y., Amano, I., Kokubo, M., Haijima, A., Miyazaki, W., et al. (2018) In Utero and Postnatal Propylthiouracil-Induced Mild Hypothyroidism Impairs Maternal Behavior in Mice. Frontiers in Endocrinology, 9, Article No. 228. [Google Scholar] [CrossRef] [PubMed]
[15] de-Miranda, A.S., Kuriyama, S.N., da-Silva, C.S., do-Nascimento, M.S.C., Parente, T.E.M. and Paumgartten, F.J.R. (2016) Thyroid Hormone Disruption and Cognitive Impairment in Rats Exposed to PBDE during Postnatal Development. Reproductive Toxicology, 63, 114-124. [Google Scholar] [CrossRef] [PubMed]
[16] Lasley, S.M. and Gilbert, M.E. (2011) Developmental Thyroid Hormone Insufficiency Reduces Expression of Brain-Derived Neurotrophic Factor (BDNF) in Adults but Not in Neonates. Neurotoxicology and Teratology, 33, 464-472. [Google Scholar] [CrossRef] [PubMed]
[17] Hosseini, M., Ghasemi, S., Hadjzadeh, M.A.R., Ghorbani, A., Aghili, S., Aghaei, A., et al. (2018) Administration of Nigella sativa during Neonatal and Juvenile Growth Period Improved Liver Function of Propylthiouracil-Induced Hypothyroid Rats. The Journal of Maternal-Fetal & Neonatal Medicine, 33, 718-725. [Google Scholar] [CrossRef] [PubMed]
[18] Yu, W., Wu, N., Li, L., Wang, J., Ouyang, H. and Shen, H. (2020) Side Effects of PTU and MMI in the Treatment of Hyperthyroidism: A Systematic Review and Meta-Analysis. Endocrine Practice, 26, 207-217. [Google Scholar] [CrossRef] [PubMed]
[19] Lo, J.C., Rivkees, S.A., Chandra, M., Gonzalez, J.R., Korelitz, J.J. and Kuzniewicz, M.W. (2015) Gestational Thyrotoxicosis, Antithyroid Drug Use and Neonatal Outcomes within an Integrated Healthcare Delivery System. Thyroid, 25, 698-705. [Google Scholar] [CrossRef] [PubMed]
[20] Bunker, S.K., Dandapat, J., Chainy, G.B.N., Sahoo, S.K. and Nayak, P.K. (2017) Neonatal Exposure to 6-N-Propyl-Thiouracil, an Anti-Thyroid Drug, Alters Expression of Hepatic DNA Methyltransferases, Methyl CpG-Binding Proteins, Gadd45a, p53, and PCNA in Adult Male Rats. European Thyroid Journal, 6, 281-291. [Google Scholar] [CrossRef] [PubMed]
[21] Andersen, S.L., Olsen, J. and Laurberg, P. (2016) Antithyroid Drug Side Effects in the Population and in Pregnancy. The Journal of Clinical Endocrinology & Metabolism, 101, 1606-1614. [Google Scholar] [CrossRef] [PubMed]
[22] Wang, Z., Haange, S., Haake, V., Huisinga, M., Kamp, H., Buesen, R., et al. (2023) Assessing the Influence of Propylthiouracil and Phenytoin on the Metabolomes of the Thyroid, Liver, and Plasma in Rats. Metabolites, 13, Article No. 847. [Google Scholar] [CrossRef] [PubMed]
[23] Hudzik, B. and Zubelewicz‐Szkodzinska, B. (2016) Antithyroid Drugs during Breastfeeding. Clinical Endocrinology, 85, 827-830. [Google Scholar] [CrossRef] [PubMed]
[24] Korkmaz, F.N., Yilmaz-Oral, D., Asker, H., Guven, B., Turkcan, D., Kirlangic, O.F., et al. (2023) Combined Levothyroxine and Testosterone Treatment for Restoring Erectile Dysfunction in Propylthiouracil-Induced Hypothyroid Rats. The Journal of Sexual Medicine, 20, 732-741. [Google Scholar] [CrossRef] [PubMed]

为你推荐