Apostoli Pietro, Catalani Simona
Department of Experimental and Applied Medicine, Unit of Occupational Medicine and Industrial Hygiene, University of Brescia, P. le Spedali Civili, 1, I-25123 Brescia, Italy.
Met Ions Life Sci. 2011;8:263-303.
Many metal ions (lead, mercury, arsenic, cadmium, chromium, nickel, vanadium, copper, lithium) exert a wide variety of adverse effects on reproduction and development, including influence on male and female subfertility or fertility, abortions, malformations, birth defects, and effects on the central nervous system. The effects produced by metal ions depend on several factors, such as timing and duration of exposure, their distribution and accumulation in various organs (e.g., the nervous system), and on the interference with specific developmental processes. Neonatal and early postnatal periods are lifespan segments during which sensitivity to metals is high; e.g., lead toxicity on the developing organism is paradigmatic of related well known and still open questions. In more recent decades, important mechanisms of action have been suggested: the endocrine disruption via impact of metal ions on reproductive hormones and the oxidative stress. While experimental data provide clear evidence of effects of many metals, human data are scant and traditionally limited to high levels of a few metal ions, like lead on male fertility. Less documented are reproductive effects for mercury, manganese, chromium, nickel, and arsenic for the same gender. More complex is the demonstration of effects on female reproduction and on pregnancy. The action of lead, arsenic, cadmium, chromium, and mercury may in fact be relevant in several stages, beginning in fetal life, during early development or maturity, and is characterized by subfertility, infertility, intrauterine growth retardation, spontaneous abortions, malformations, birth defects, postnatal death, learning and behavior deficits, and premature aging. Also, for females the evidences of specific aspects such as fertility or abortions are usually higher and clearer from animal experiments than from human studies.
许多金属离子(铅、汞、砷、镉、铬、镍、钒、铜、锂)对生殖和发育会产生各种各样的不良影响,包括对男性和女性生育能力低下或生育能力的影响、流产、畸形、出生缺陷以及对中枢神经系统的影响。金属离子产生的影响取决于几个因素,如接触的时间和持续时间、它们在各个器官(如神经系统)中的分布和积累,以及对特定发育过程的干扰。新生儿期和出生后早期是对金属敏感度较高的生命阶段;例如,铅对发育中生物体的毒性就是相关的著名且仍未解决问题的典型例子。在最近几十年里,人们提出了重要的作用机制:金属离子通过影响生殖激素导致内分泌紊乱以及氧化应激。虽然实验数据清楚地证明了许多金属的影响,但人类数据却很少,而且传统上仅限于少数几种金属离子的高剂量情况,比如铅对男性生育能力的影响。对于汞、锰、铬、镍和砷对同一性别生殖方面的影响,记录较少。对女性生殖和怀孕影响的证明更为复杂。事实上,铅、砷、镉、铬和汞的作用可能在从胎儿期开始的几个阶段都很重要,在早期发育或成熟期间,其特征表现为生育能力低下、不育、宫内生长迟缓、自然流产、畸形、出生缺陷、出生后死亡、学习和行为缺陷以及早衰。此外,对于女性来说,诸如生育能力或流产等特定方面的证据通常在动物实验中比在人体研究中更丰富、更清晰。