Pryor J L, Hughes C, Foster W, Hales B F, Robaire B
University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Environ Health Perspect. 2000 Jun;108 Suppl 3(Suppl 3):491-503. doi: 10.1289/ehp.00108s3491.
Drugs and environmental chemicals can adversely affect the reproductive system. Currently, available data indicate that the consequences of exposure depend on the nature of the chemical, its target, and the timing of exposure relative to critical windows in development of the reproductive system. The reproductive system is designed to produce gametes in far greater excess than would seem to be necessary for the survival of species. Ten to hundreds of millions of spermatozoa are generated daily by most adult male mammals, yet very few of these germ cells succeed in transmitting their genetic material to the next generation. Although the number of oocytes produced in mammalian females is more limited, and their production occurs only during fetal life, most ovaries contain several orders of magnitude more oocytes than ever will be fertilized. Toxicant exposures may affect critical events in the development of the reproductive system, ranging from early primordial germ cell determination to gonadal differentiation, gametogenesis, external genitalia, or signaling events regulating sexual behavior. Although there are differences between the human reproductive system and that of the usual animal models, such models have been extremely useful in assessing risks for key human reproductive and developmental processes. The objectives for future studies should include the elucidation of the specific cellular and molecular targets of known toxicants; the design of a systematic approach to the identification of reproductive toxicants; and the development of sensitive, specific, and predictive animal models, minimally invasive surrogate markers, or in vitro tests to assess reproductive system function during embryonic, postnatal, and adult life.
药物和环境化学物质会对生殖系统产生不利影响。目前，现有数据表明，接触的后果取决于化学物质的性质、其作用靶点以及相对于生殖系统发育关键窗口期的接触时间。生殖系统的设计目的是产生数量远远超过物种生存所需的配子。大多数成年雄性哺乳动物每天会产生数以千万计到数以亿计的精子，但这些生殖细胞中只有极少数能够成功地将其遗传物质传递给下一代。虽然哺乳动物雌性产生的卵母细胞数量较为有限，且仅在胎儿期产生，但大多数卵巢中所含的卵母细胞数量比最终受精的卵母细胞数量多几个数量级。接触有毒物质可能会影响生殖系统发育中的关键事件，从早期原始生殖细胞的确定到性腺分化、配子发生、外生殖器发育，或调节性行为的信号传导事件。尽管人类生殖系统与常见动物模型的生殖系统存在差异，但这些模型在评估人类关键生殖和发育过程的风险方面一直极为有用。未来研究的目标应包括阐明已知有毒物质的具体细胞和分子靶点；设计一种系统方法来识别生殖有毒物质；以及开发敏感、特异且具有预测性的动物模型、微创替代标志物或体外试验，以评估胚胎期、出生后和成年期生殖系统的功能。
