الفهرس 
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Abstract
A) Oceanographic study:
The potential ecological effects of rising levels of heavy metals concentrations in the environment are of great concern due to their highly bio-accumulative nature, persistent behavior and higher toxicity. These chemicals biomagnify in the food chain and impose various toxic effects in aquatic organisms. Molluscs reflect the higher degree of environmental contamination by heavy metals and are the most useful bio-indicator tools. Several studies and research work have been cited to establish and evaluate the relationship between metal contents of water column, sediment fractions, suspended matter and mollusc tissue concentrations. The metals body burden in molluscs may reflect the concentrations of metals in surrounding water and sediment, and may thus be an indication of quality of the surrounding environment. The first objective of this work is to gather more information on the use of molluscs as cosmopolitan bio-indicators for heavy metal pollution in aquatic ecosystems through the estimation of metallothionein concentration in mussel tissues as well as cadmium and lead.
The present results indicated that the studied area was contaminated with some heavy metals such as cadmium and lead which were in agreement with many previous studies, which proved that Alexandria coast contaminated with many heavy metals like cadmium, nickel, cobalt, and aluminum. Meanwhile, the present study proved the presence of measurable amounts of metallothionein in mussels collected from the studied area.
Metallothioneins are inducible proteins. Heavy metal cations accumulated within the cells stimulate metalloprotein biosynthesis by enhancing metallothionein gene transcription. The MT-mRNA is translated by cytosolic free ribosome, leading to an increase in apo- metallothionein that will rapidly react with free metal cations present in the cytosol. Due to their biochemical and functional characteristics, metallothioneins are able to protect cell structures from non-specific interactions with heavy metal cations and to detoxify metal excess penetrating into the cell. Due to their inducibility to heavy metals, metallothioneins are usually considered an important specific biomarker to detect organism response to inorganic pollutants such as Cd, Hg, Cu, and Zn present in the aquatic environment.
B) Biochemical study:
In about 50-60% of recurrent pregnancy losses, a causative factor cannot be identified and are therefore classified as idiopathic. Since, the exposure to environmental genotoxic pollutants may participate in the induction of idiopathic spontaneous abortion. Consequently, the present study was endeavored to (a) detect, if the spontaneous aborted women were exposed to any of the genotoxic pollutants as the heavy metals cadmium and lead or not and to (b) elucidate the mechanism of action by which cadmium and lead induce spontaneous abortion through the determination of: 1- blood cadmium and lead levels, 2- serum malondialdhyde, as a biomarker for determining oxidative stress, 3- reduced glutathione and catalase enzyme activity as biomarkers of antioxidant defense mechanisms, 4- endocrine disruptor effect of cadmium and lead through the determination of serum progesterone hormone, 5- metallothionein concentration which has antioxidant and antiapoptotic properties and 6- the hemostatic effect of cadmium and lead through the determination of blood haemoglobin, mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH).
The current study was conducted on 76 women divided into 4 groups. Group I comprised 18 normal control women with no history of miscarriage. Group II, III, IV involved 24, 18 and 16 women with a history of 2, 3 and more spontaneous abortions, respectively.
The results of the present study revealed, that there was a highly significant increase in the level of blood cadmium and lead in the three studied groups of spontaneous aborters than that of the corresponding control. This finding proved that the patients recruited in the present study were exposed to the environmental heavy metals cadmium and lead. There are two aspects of cadmium and lead toxicity, both of which are well documented clinically. (1) is the interference with iron absorption by cadmium and lead, (2) is the effect of cadmium and lead toxicity on the iron status. The former is illustrated by the development of microcytic hypochromic anemia as a result of cadmium and lead exposure. The latter is best portrayed by the illness, ITAI-ITAI (bone lesions and anemia), described in Japan in individuals drinking water of high cadmium content. Interactions between iron and these metals appear to be implicated in both effects. It appears that cadmium in some way blocks the transferrin cycle, which leads to impaired iron absorption.
The aforementioned findings confirmed and represented a very good interpretation to the results of the current study, which elucidated, that the three studied groups of aborted women were exposed to the environmental cadmium and lead pollution, which induced impairment of iron storage, as well as microcytic hypochromic anemia manifested by significant decrease in the level of MCV as well as MCH. A large body of work exists outlining the effects of cadmium on gametogenesis in both males and females, and implicating its compounds in early embryo lethality and implantation failure.
The results of the present study depicted, that the three studied groups of patients had highly significant elevated levels of serum malondialdehyde, associated with highly significant decrease in the levels of antioxidant parameters, glutathione and catalase enzyme activity. Therefore, the aborted women in this study suffered from oxidative stress, and it may be suggested, that exposure to cadmium and lead enhanced lipid peroxidation, which may end in spontaneous abortion. Hence, it may be indicated, that lipid peroxidation is an early and sensitive consequence of cadmium and lead exposure. It is postulated, that lipid peroxidation may occur as a direct effect of cadmium and lead, through inducing displacement of redox metal ion or decrease in glutathione content. The glutathione redox system is also deeply involved in embryogenesis. Preimplanted embryos are very sensitive to conditions that cause oxidative stress.
Metallothionein (MT) perhaps plays the most important role in intracellular metal binding. There is evidence that lead and cadmium are able to induce MT synthesis in placenta. The results of the present study showed highly significant increase in the level of metallothionein in the blood of all aborted women groups than that of control group.
Cadmium and lead are known to get accumulated in the placenta, which therefore act as an important, but not complete barrier to protect the fetus from toxic effects of those metals. The decrease in the serum progesterone levels of the aborted women in the current study may be attributable to the perturbations of cadmium and lead in placental and ovarian steriodogenesis. Mechanisms, by which cadmium and lead may exert their effects, are altered intracellular trafficking of cholesterol into mitochondria, altered activities of P450scc or 3-hydroxysteroid dehydrogenase, and/or interference with zinc finger motif on DNA transcription.
Earlier, it has been demonstrated, that combined exposure to lead and cadmium affects steriodogenesis by the decrease in receptor binding by the gonadotropins, which is attributed to membrane alteration caused by oxidative stress in non-pregnant stages. Moreover, cadmium and lead has been postulated to decrease the placental syncitiotrophoblastic secretion of progesterone, a hormone vital to early pregnancy maintenance. Given that progesterone plays a key role in maintaining myometrial quiescence, the down regulation of placental progesterone synthesis may provide a mechanistic basis for the association between cadmium and lead and miscarriage.