الفهرس 
Introduction and Aim of the work
Intra uterine growth retardation (IUGR)Only 14 pages are availabe for public view
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Abstract
Forty eight adult female rats were randomly and equally divided into four groups: the first group (control group) received distilled water at a comparable dose, route and for the same duration, the second group (lead group) was exposed to 500 mg/kg lead in drinking water daily form GD0 till delivery. The animals of third group (vitamin E group) were exposed to lead at the same dose, route and duration as the second group associated with simultaneous administration of 250 mg/kg Vit E orally by gastric tube daily at 1 p.m. The rats of fourth group (melatonin group) were exposed to lead at the same dose, route and duration as the second group simultaneously with 10 mg/kg melatonin subcutaneously daily at 5 p.m. (2 h before lights-off).
Half number of dams were allowed to deliver spontaneously, the day of delivery was defined as postnatal day 0 (PND0) then dams and their pups were weighed and pups were counted at PND0. Thereafter these pups were preserved for following up their body weights (BW) and pups survival rate after 21 days (PND21) to clarify if the effect of exposure to lead during pregnancy was continuous postnatal or not. Another half of dams were preserved until the day 18 (GD18) of pregnancy then laparotomy (Nakajima et al., 2008) was done to gain the placenta for weighing, histopathological studying and measuring placenta lead concentration in each. The feti of laparotomy dams were sacrificed for collecting blood sample pool.
The BW of each female rat just after delivery (PND0), BW of each pup individually in each group immediately at PND0 as well at PND21, the number of living pups /dam at day 0 (PND0) and (PND21) and placental weight were recorded.
The following biochemical parameters were measured in maternal and fetus sera: PDGF, NO, TLP, TAC, OSI. In addition, placental lead concentrations and a histopathological examination of placental were done individually. Also, correlations of placental lead concentrations with F.Wt. at PND0, F.Wt. at PND21, placental weight, maternal and fetal serum levels of PDGF, NO, TLP, TAC and OSI in lead group were detected.
In this study, no significant change of M.Wt. at PND0 in all groups was recorded. While, P.Wt. significantly decreased in lead group at PND0 and PND21 as well as pups survival rate at PND21 and placental weight also decreased that verify the suppression effect of lead on fetal growth during pregnancy as well as during follow up period at (PND21). Treatment with Vit E and melatonin improved significantly these injurious effects.
Moreover, exposure to lead during pregnancy reduced serum level of maternal & fetal PDGF and TAC while, it increased NO, TLP and OSI. Treatment with Vit E and melatonin ameliorated the changes in these parameters.
The possible pathophysiological mechanisms involved in lead induced IUGR may be mediated by decreasing PDGF that responsible for placental development through promoting the growth of trophoblasts. Also, PDGF plays a role in embryonic development, cell proliferation, cell migration and angiogenesis. While the increase NO production in case of IUGR can be considered a compensatory response to maintain haemostasis thus improving blood flow in the feto-placental unit.
In addition, the recorded high TLP and OSI could be considered contributors to IUGR as they induce cell-membrane dysfunction, DNA damage, and apoptosis. Also, they inhibit free radical scavenging enzymes leading to accumulation of ROS. Also, it causes direct or indirect damage to mitochondria by depleting the endogenous thiol-containing antioxidant glutathione.
Therefore supplementation with antioxidants as Vit E and melatonin can protect against the adverse effects of oxidative stress by scavenging, breaking down these free radicals and stimulating antioxidant enzyme systems as well as improve blastocyst development and fetal growth.
Besides, increase placental lead concentration, focal necrosis, vacuolation and degeneration found in all layers of lead exposed placentas prove the damaging effects of lead and added another pathophysiological explanation of lead induced IUGR. Prophylactic application of Vit E and melatonin can ameliorate lead-induced structural alterations in placenta. Also, they can reduce accumulation of lead in the tissue by enhancing lead metabolism and increase its mobilization into urine.
A positive correlations were recorded between placental lead concentrations in lead exposed group with maternal and fetal levels of NO, TLP and OSI. Significant negative correlations found between placental lead concentrations in lead treated group with maternal and fetal levels of PDGF and TAC. While there were non-significant negative relations between lead concentrations in placenta and P.Wt. at PND0 and PND21 and with placental weight.
Melatonin was more efficient than Vit E in improving the detrimental effects of lead on P.Wt. at PND0 and PND21, pups survival rate % at PND21, PDGF, maternal NO, TLP, TAC, OSI and placental histopathological study.
Maternal serum levels of NO and TLP were higher than that of fetus. These results could be explained by the sufficient levels of antioxidant capacity in the fetal blood and the presence of placental barrier that adequate to shield the fetus from oxidative injury. However, PDGF is higher in fetus than maternal serum in all studied groups supporting its role in establishing normal physiological growth of fetus. However, there are no significant changes in TAC and OSI between maternal and fetal serum.