School of Public Health, University of California, Berkeley, CA 94720, USA.
Mutat Res. 2011 Nov-Dec;728(3):118-38. doi: 10.1016/j.mrrev.2011.07.003. Epub 2011 Jul 20.
Formaldehyde, the recently classified carcinogen and ubiquitous environmental contaminant, has long been suspected of causing adverse reproductive and developmental effects, but previous reviews were inconclusive, due in part, to limitations in the design of many of the human population studies. In the current review, we systematically evaluated evidence of an association between formaldehyde exposure and adverse reproductive and developmental effects, in human populations and in vivo animal studies, in the peer-reviewed literature. The mostly retrospective human studies provided evidence of an association of maternal exposure with adverse reproductive and developmental effects. Further assessment of this association by meta-analysis revealed an increased risk of spontaneous abortion (1.76, 95% CI 1.20-2.59, p=0.002) and of all adverse pregnancy outcomes combined (1.54, 95% CI 1.27-1.88, p<0.001), in formaldehyde-exposed women, although differential recall, selection bias, or confounding cannot be ruled out. Evaluation of the animal studies including all routes of exposure, doses and dosing regimens studied, suggested positive associations between formaldehyde exposure and reproductive toxicity, mostly in males. Potential mechanisms underlying formaldehyde-induced reproductive and developmental toxicities, including chromosome and DNA damage (genotoxicity), oxidative stress, altered level and/or function of enzymes, hormones and proteins, apoptosis, toxicogenomic and epigenomic effects (such as DNA methylation), were identified. To clarify these associations, well-designed molecular epidemiologic studies, that include quantitative exposure assessment and diminish confounding factors, should examine both reproductive and developmental outcomes associated with exposure in males and females. Together with mechanistic and animal studies, this will allow us to better understand the systemic effect of formaldehyde exposure.
甲醛是一种最近被分类为致癌物质和普遍存在的环境污染物，长期以来一直被怀疑会对生殖和发育产生不良影响，但之前的综述结果并不一致，部分原因是许多人群研究在设计上存在局限性。在当前的综述中，我们系统地评估了在同行评审文献中，甲醛暴露与人类和体内动物研究中的不良生殖和发育影响之间的关联证据。大多数回顾性的人类研究提供了母体暴露与不良生殖和发育影响之间关联的证据。通过荟萃分析进一步评估这种关联显示，暴露于甲醛的女性自发性流产的风险增加（1.76，95%CI 1.20-2.59，p=0.002），所有不良妊娠结局的综合风险增加（1.54，95%CI 1.27-1.88，p<0.001），尽管不能排除差异回忆、选择偏差或混杂因素。对包括所有暴露途径、研究剂量和剂量方案的动物研究的评估表明，甲醛暴露与生殖毒性之间存在正相关，主要发生在雄性。甲醛诱导生殖和发育毒性的潜在机制，包括染色体和 DNA 损伤（遗传毒性）、氧化应激、酶、激素和蛋白质水平和/或功能改变、细胞凋亡、毒代基因组学和表观基因组学效应（如 DNA 甲基化），已经被确定。为了阐明这些关联，应进行设计良好的分子流行病学研究，包括定量暴露评估和减少混杂因素，以检查与男性和女性暴露相关的生殖和发育结局。与机制和动物研究一起，这将使我们能够更好地理解甲醛暴露的全身效应。
