engleski

Reproductive and developmental toxicity of metals

Metals exert a wide variety of adverse effects on reproduction and development including influence on fertility, intrauterine growth retardation, abortions, malformations, birth defects, and developmental effects, mainly those on the nervous system. Metals may affect reproduction or development directly, at relatively low doses, or indirectly through systemic toxicity, generally at higher doses. More recent, important mechanisms of action are those related to endocrine disruption and oxidative stress. The effects produced by metals depend on several factors, such as the timing and duration of exposure, their distribution and accumulation in various organs (e.g., the nervous system), and on the ability to interfere with specific developmental processes. Interesting interactions between environmental and congenital factors have been documented ; genetic polymorphisms can affect fetal susceptibility to teratogens or maternal ability to detoxify and excrete xenobiotics. //Male reproductive effects of high doses of many metals have been observed in animals, whereas there is still insufficient evidence to the human male concerning a quantitative dose-response relationship. This could be partly explained by considerable interspecies differences in susceptibility to reproductive toxicity and in the route, level, and duration of metal exposure. Human studies have provided substantial evidence of effects for only a few metals. These include lead-induced effects on male fertility and certain parameters of semen quality, even at moderate exposure levels, effects by cadmium on prostate impairment and serum testosterone, and less well-documented male reproductive effects of mercury, manganese, chromium, nickel, and arsenic at levels significantly lower than those that cause systemic toxicity. //The effects of metals on female reproduction may arise from their action on several stages beginning in fetal life, during early development or maturity, and include manifestations such as subfertility, infertility, intrauterine growth retardation, spontaneous abortions, malformations, birth defects, postnatal death, learning and behavior deficits, and premature aging ; evidence is usually limited to animal data or studies on fertility and spontaneous abortions. The clinical and epidemiological findings related to metal-induced effects on female reproduction are often difficult to interpret, because many other factors may influence the outcome such as age, ovarian reserve, hormonal imbalance, behavior, genetics, male fertility factors, and sexually transmitted diseases.. //Exposure to metals during organogenesis may cause fetal anomalies, whereas exposure during other periods of development may result in embryo or fetal lethality or other developmental effects. Teratogenesis bioassays in rodents (hamsters, mice, or rats) have yielded positive results for the compounds of many metals (Al, As, Bo, Cd, Co, Cr, Cu, Ga, Hg, Li, Mn, Ni, Pb, Se, U, V, and Zn), producing fetal and early postnatal deaths, as well as malformations such as anencephaly, eye defects, cleft palate, and skeletal anomalies .The relevance of these findings to human exposure is, however, still unclear. //Neonatal and early postnatal periods are lifespan segments during which sensitivity to metals is high, and lead toxicity on the developing organism represents an illustrative example for related problems and questions. In the last decade, children&#8217; s blood lead (PbB) levels have declined significantly in a number of countries, and current prevalent mean levels in developed countries are <50 &micro ; g/L. Despite this reduction, childhood lead poisoning continues to be a public health problem for certain high-risk groups. Recent studies have extended the association of blood lead and intellectual impairment to PbB levels <100 &micro ; g/L and now challenge the safety of this level that for more than a decade has served as a community alert level for preventive action. The recent studies cast doubt whether a toxicological threshold and no-effect value exists for lead related developmental toxicity. This chapter focuses on the reproductive and developmental effects by metals of traditional interest for toxicologists, such as lead, mercury, and cadmium, but also provides information, where available, on chromium, arsenic, manganese, and nickel, and on metals of more recent interest such as aluminum, platinum, vanadium, lithium, and uranium.

toxic metals, male reproductive effects, female reproductive effects, developmental effects of prenatal exposure, developmental effects from neonatal exposure

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