Metal ions affecting reproduction and development.
ABSTRACT 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.
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ABSTRACT: Nickel is associated with reproductive toxicity. However, the reproductive toxicity of nickel nanoparticles (Ni NPs) is unclear. Our goal was to determine the association between nickel nanoparticle exposure and reproductive toxicity. According to the one-generation reproductive toxicity standard, rats were exposed to nickel nanoparticles by gavage and we selected indicators including sex hormone levels, sperm motility, histopathology, and reproductive outcome etc. Experimental results showed nickel nanoparticles increased follicle stimulating hormone (FSH) and luteinizing hormone (LH), and lowered etradiol (E2) serum levels at a dose of 15 and 45 mg/kg in female rats. Ovarian lymphocytosis, vascular dilatation and congestion, inflammatory cell infiltration, and increase in apoptotic cells were found in ovary tissues in exposure groups. For male rats, the weights decreased gradually, the ratio of epididymis weight over body weight increased, the motility of rat sperm changed, and the levels of FSH and testosterone (T) diminished. Pathological results showed the shedding of epithelial cells of raw seminiferous tubule, disordered arrangement of cells in the tube, and the appearance of cell apoptosis and death in the exposure group. At the same time, Ni NPs resulted in a change of the reproductive index and the offspring development of rats. Further research is needed to elucidate exposure to human populations and mechanism of actions.International Journal of Molecular Sciences 11/2014; 15(11):21253-69. DOI:10.3390/ijms151121253 · 2.46 Impact Factor
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ABSTRACT: To our knowledge, this study may be the first to examine the antagonistic role of selenium (Se) on oxidative stress induced by cadmium (Cd) and its impact on birth measures. Cd and Se levels were measured in umbilical-cord blood and the placentas of a subsample of 250 healthy mothers who participated between 2005 and 2006 in the project “Prenatal Exposure to Pollutants”. The median Cd levels in cord and maternal blood and placental tissue were 0.78 μg/l, 0.976 μg/l and 0.037 μg/g dry wt., respectively. The median levels of Se in cord serum and placental tissue were 65.68 μg/l and 1.052 μg/g dry wt., respectively. Se was more than 100-fold in molar excess over Cd in both cord serum and placental tissue. The median molar Cd/Se ratios in cord serum and placental tissue were 0.008 and 0.024, respectively, which were much lower than unity. This study suggests that both Cd and Se play a role in the mechanism of oxidative stress, but, the process underlying this mechanism remains unclear. Nevertheless, three biomarkers of oxidative stress had inconsistent relationships with Cd and/or Se in various matrices, perhaps due to potential untested confounders. Our results generally support an association between low in utero exposure to Cd and the anthropometric development of the fetus. Adjusted regression models indicated a negative association of cord blood Cd levels ≥0.78 μg/l with Apgar 5-min scores and birth height. Maternal Cd levels ≥0.976 μg/l were associated with a 5.94-fold increased risk of small-for-gestational-age births, which increased to 7.48-fold after excluding preterm births. Placenta weight decreased with increasing placental Cd levels ≥0.037 μg/g dry wt. (p = 0.045), an association that became stronger after excluding preterm births or adjusting for birth weight. Cord Se levels ≥65.68 μg/l were positively associated with placenta weight (p = 0.041) and thickness (p = 0.031), an association that remained unchanged after excluding preterm births. Cord Se levels, however, were negatively associated with cephalization index, but only after excluding preterm births (p = 0.017). Each birth measure was again modeled as a function of the Cd/Se ratios in cord blood and placenta tissue. Interestingly cord ratios ≥0.008 were negatively associated with Apgar-5 min score (p = 0.047), birth weight (p = 0.034) and placenta thickness (p = 0.022). After excluding preterm births, only the association with placenta thickness remained significant (p = 0.021), while birth weight (p = 0.053) was marginally significant. In contrast, cephalization index increased with Cd/Se ratios ≥0.008 (p = 0.033), an association that became marginally significant after excluding preterm births (p = 0.058). For placental Cd/Se ratios ≥0.024, only placenta weight was reduced with (p = 0.037) and without (p = 0.009) the inclusion of preterm births. These findings do not support an antagonistic mechanism between Cd and Se. The role of oxidative mechanisms either induced by Cd exposure or alleviated by Se on these birth anthropometric measures was examined by principal component analysis. Se did not have a clear protective role against Cd-induced adverse effects despite its substantial excess over Cd, and its role in alleviating oxidative stress by reducing malondialdehyde levels. The results may suggest that the extent of the Se beneficial effects is not governed only by its concentration but also by the chemical forms of Se that interact with various proteins. Consequently, the speciation of Se in such studies is essential for understanding and predicting Se availability for absorption.International Journal of Hygiene and Environmental Health 09/2014; 218(1). DOI:10.1016/j.ijheh.2014.08.001 · 3.28 Impact Factor
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ABSTRACT: The aim of the present study was to investigate the toxic effect of prolonged lead exposure on the chromosomal and testicular tissue of male rabbits. Twenty mature male New Zealand rabbits were used in four groups, the first group kept as a control. The second, third and fourth groups received low (15mg/kg b.wt), medium (20mg/kg b.wt) and high (30mg/kg b.wt) doses of lead acetate, respectively. Lead acetate was given by oral route for 12 weeks (five days a week). By the end of the experiment, animals were injected with colchicine 3 h before slaughtering.The epididymis were excised and sperm was collected for morphological abnormalities of the sperm shape. Bone marrow metaphases were prepared and scored for chromosomal aberrations. Also pathological examination of the testes and epidedemis were examined. Result revealed a statistically significant (p < 0.01) increase in the number of abnormal sperm in treated animals at the three tested doses. Lead acetate at the three doses increased the percentage of chromosomal abnormalities.Pathological examination of testicular tissues showed degenerative changes of spermatogonia and spermatocytes to advanced degeneration and vacuolation with pyknosis and necrosis of spermatogonia and setoli cells. The hyaline degeneration and edema in the center of semniferous tubules were detected and in high dose, the lumen of semineferous tubules showed atrophied and free from spermatocytes. In conclusion, lead acetate has genotoxic and cytotoxic effect in male rabbit and may contribute in reduction of fertility.