Gestational lead exposure induces developmental abnormalities and up-regulates apoptosis of fetal cerebellar cells in rats.
Lead (Pb), a known environmental toxicant, adversely affects almost all organ systems. In this study, we investigated the effects of maternal lead exposure on fetal rat cerebellum. Female Sprague-Dawley rats were given lead nitrate in drinking water (0, 0.5, and 1%) for two weeks before conception, and during pregnancy. Fetuses were collected by caesarian section on gestational day 21 and observed for developmental abnormalities. The fetal cerebellar sections from control and 1% lead group were stained with cresyl violet. Immunohistochemical expressions of p53, Bax, Bcl-2, and caspase 3 were quantified by AnalySIS image analyzer (Life Science, Germany). Lead exposure induced developmental abnormalities of eyes, ear, limbs, neck and ventral abdominal wall; however, these abnormalities were commonly seen in the 1% lead-treated group. In addition, lead also caused fetal mortality and reduced body growth in both dose groups and reduced brain weight in the 1% lead-treated group. The fetal cerebella from the 1% lead-treated group showed unorganized cerebellar cortical layers, and degenerative changes in granule and Purkinje cells such as the formation of clumps of Nissl granules. An increase in Bax and caspase 3, and a decrease in Bcl-2 (p < 0.05), but not in p53, showed apoptosis of the neurons. In conclusion, gestational lead exposure in rats induces fetal toxicity and developmental abnormalities. The lead exposure also impairs development of cerebellar layers, induces structural changes, and apoptosis in the fetal cerebellar cortex. These results suggest that lead exposure during gestation is extremely toxic to developing cerebellum in rats.
Department of Anatomy, Faculty of Medicine, Kuwait University , Kuwait.
Alyaa M
AM
Mousa
Ameera S
AS
Al-Fadhli
Muddanna S
MS
Rao
Narayana
N
Kilarkaje
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002525:Cerebellar Cortex / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D000013:Congenital Abnormalities / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D007150:Immunohistochemistry; D007854:Lead / Q000633:toxicity*; D018811:Maternal Exposure / Q000009:adverse effects*; D009566:Nitrates / Q000633:toxicity*; D038081:Organogenesis / Q000187:drug effects*; D011247:Pregnancy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
C494828:Bax protein, rat; D004785:Environmental Pollutants; D009566:Nitrates; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D007854:Lead; C017461:lead nitrate
Caspase 3; developmental neuropathology; embryotoxicity; heavy metals; p53; pro-apototic proteins; teratogenesis