Lemasters G K, Perreault S D, Hales B F, Hatch M, Hirshfield A N, Hughes C L, Kimmel G L, Lamb J C, Pryor J L, Rubin C, Seed J G
University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Environ Health Perspect. 2000 Jun;108 Suppl 3(Suppl 3):505-9. doi: 10.1289/ehp.00108s3505.
This work group report addresses the central question: What are the critical windows during development (preconception through puberty) when exposure to xenobiotics may have the greatest adverse impact on subsequent reproductive health? The reproductive system develops in stages, with sex-specific organogenesis occurring prenatally and further maturational events occurring in the perinatal period and at puberty. Complex endocrine signals as well as other regulatory factors (genetics, growth factors) are involved at all stages. Evidence from animal models and human studies indicates that many specific events can be perturbed by a variety of toxicants, with endocrine-mediated mechanisms being the more widely studied. Prioritized research needs include basic studies on the cellular-molecular and endocrine regulation of sexual differentiation and development; increased efforts regarding potential adverse effects on development in females, including breast development; expanded animal studies on different classes of chemicals, comparing responses during development (prenatal and postnatal) with responses in adults; and, more extensive explorations regarding the reproductive biology and toxicology of puberty in humans.
在发育过程（从受孕前到青春期）中，接触外源性物质可能对后续生殖健康产生最大不利影响的关键窗口期是什么？生殖系统分阶段发育，性别特异性器官发生在产前阶段，围产期和青春期则发生进一步的成熟事件。所有阶段都涉及复杂的内分泌信号以及其他调节因子（遗传学、生长因子）。动物模型和人体研究的证据表明，许多特定事件会受到多种毒物的干扰，其中内分泌介导的机制得到了更广泛的研究。优先研究需求包括关于性别分化和发育的细胞分子及内分泌调节的基础研究；加大对女性发育潜在不利影响的研究力度，包括乳腺发育；扩大对不同类别化学物质的动物研究，比较发育过程（产前和产后）中的反应与成年期的反应；以及对人类青春期生殖生物学和毒理学进行更广泛的探索。
