Bloise E, Ortiga-Carvalho T M, Reis F M, Lye S J, Gibb W, Matthews S G
Laboratory of Translational Endocrinology, Biophysics Institute Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil Department of Morphology, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Laboratory of Translational Endocrinology, Biophysics Institute Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Hum Reprod Update. 2016 Mar-Apr;22(2):164-81. doi: 10.1093/humupd/dmv049. Epub 2015 Nov 5.
The transmembrane ATP-binding cassette (ABC) transporters actively efflux an array of clinically relevant compounds across biological barriers, and modulate biodistribution of many physiological and pharmacological factors. To date, over 48 ABC transporters have been identified and shown to be directly and indirectly involved in peri-implantation events and fetal/placental development. They efflux cholesterol, steroid hormones, vitamins, cytokines, chemokines, prostaglandins, diverse xenobiotics and environmental toxins, playing a critical role in regulating drug disposition, immunological responses and lipid trafficking, as well as preventing fetal accumulation of drugs and environmental toxins.
This review examines ABC transporters as important mediators of placental barrier functions and key reproductive processes. Expression, localization and function of all identified ABC transporters were systematically reviewed using PubMed and Google Scholar websites to identify relevant studies examining ABC transporters in reproductive tissues in physiological and pathophysiological states. Only reports written in English were incorporated with no restriction on year of publication. While a major focus has been placed on the human, extensive evidence from animal studies is utilized to describe current understanding of the regulation and function of ABC transporters relevant to human reproduction.
ABC transporters are modulators of steroidogenesis, fertilization, implantation, nutrient transport and immunological responses, and function as 'gatekeepers' at various barrier sites (i.e. blood-testes barrier and placenta) against potentially harmful xenobiotic factors, including drugs and environmental toxins. These roles appear to be species dependent and change as a function of gestation and development. The best-described ABC transporters in reproductive tissues (primarily in the placenta) are the multidrug transporters p-glycoprotein and breast cancer-related protein, the multidrug resistance proteins 1 through 5 and the cholesterol transporters ABCA1 and ABCG1.
The ABC transporters have various roles across multiple reproductive tissues. Knowledge of efflux direction, tissue distribution, substrate specificity and regulation of the ABC transporters in the placenta and other reproductive tissues is rapidly expanding. This will allow better understanding of the disposition of specific substrates within reproductive tissues, and facilitate development of novel treatments for reproductive disorders as well as improved approaches to protecting the developing fetus.
跨膜ATP结合盒（ABC）转运蛋白可主动将一系列临床相关化合物转运穿过生物屏障，并调节许多生理和药理因子的生物分布。迄今为止，已鉴定出超过48种ABC转运蛋白，它们直接或间接参与着床前期事件以及胎儿/胎盘发育。它们能转运胆固醇、类固醇激素、维生素、细胞因子、趋化因子、前列腺素、各种外源性物质和环境毒素，在调节药物处置、免疫反应和脂质转运，以及防止胎儿蓄积药物和环境毒素方面发挥着关键作用。
本综述将ABC转运蛋白视为胎盘屏障功能和关键生殖过程的重要调节因子进行研究。使用PubMed和谷歌学术网站系统回顾了所有已鉴定的ABC转运蛋白的表达、定位和功能，以确定在生理和病理生理状态下生殖组织中研究ABC转运蛋白的相关研究。仅纳入英文撰写的报告，对发表年份无限制。虽然主要关注人类，但也利用了动物研究的大量证据来描述目前对与人类生殖相关的ABC转运蛋白的调节和功能的理解。
ABC转运蛋白是类固醇生成、受精、着床、营养物质转运和免疫反应的调节因子，在各种屏障部位（即血睾屏障和胎盘）充当抵御潜在有害外源性物质（包括药物和环境毒素）的“守门人”。这些作用似乎因物种而异，并随妊娠和发育而变化。在生殖组织（主要是胎盘）中描述得最为清楚的ABC转运蛋白是多药转运蛋白P-糖蛋白和乳腺癌相关蛋白、多药耐药蛋白1至5以及胆固醇转运蛋白ABCA1和ABCG1。
ABC转运蛋白在多个生殖组织中具有多种作用。关于ABC转运蛋白在胎盘和其他生殖组织中的外排方向、组织分布、底物特异性和调节的知识正在迅速扩展。这将有助于更好地理解特定底物在生殖组织中的处置情况，并促进开发针对生殖障碍的新疗法以及改进保护发育中胎儿的方法。
