In Vivo and In Vitro Evidence for Placental DNA Damage in Preeclampsia
نویسندگان
چکیده
Preeclampsia (PE) is an idiopathic multisystem disease affecting 5-7% of pregnant women. Placental oxidative stress is a characteristic feature of PE and occurs when the production of reactive oxygen species (ROS) within the placenta overwhelms the intrinsic anti-oxidant defenses. We hypothesize that excessive oxidative DNA damage at the fetal-maternal interface coupled with a defective DNA damage/repair response is causally related to PE. Here we demonstrate that γH2AX (a sensitive marker of DNA damage) is expressed in the maternal decidua but not trophoblast of normal placentas, and that expression is significantly higher in PE placental tissues in vivo. Using primary in vitro cultures of maternal decidual stromal cells (DSCs) and fetal cytotrophoblast cells (CTs), we show an increase in γH2AX foci in DSCs cultured with vs without H2O2 (70.6% vs 11.6%; P<0.0001) or under hypoxia-reperfusion vs normoxia (20- vs 3-fold; P = 0.01); no foci were seen in CTs. We further demonstrate that Base Excision Repair (BER) intermediates are significantly increased in DSCs (not CTs) under these same conditions. Our data show that DNA damage is significantly more common in PE placentas, and that this DNA damage is localized to the maternal and not fetal side of the placenta. CTs may be selectively resistant to DNA damage in an effort to protect the fetus.
منابع مشابه
Thein vitro and in vivo Effect of Clinoptiloliteon Decreasing of Copper Ion and DNA Damage of Anodonta Cygnea
The ability of natural zeolite (Clinoptilolite) to remove copper from aqueous ecosystem was studied in real and laboratory conditions. Fresh water mussels (Anodonta Cygnea) of different sizes were Exposed to copper (150, 350, 450 µgl-1) for 10 days. Copper exposure induced DNA damage in the haemolymph cells of Anodonta of all sizes. In connection with real samples, the amount of damage and even...
متن کاملVaricocele Time-dependently Affects DNA Integrity of Sperm Cells: Evidence for Lower In vitro Fertilization Rate in Varicocele-positive Rats
متن کامل
Antioxidant capacity and radioprotective properties of the flavonoids galangin and kaempferide isolated from Alpinia galanga L. (Zingiberaceae) against radiation induced cellular DNA damage
Background: Alpinia galanga L. belonging to the family Zingiberaceae is widely grown in the state of Kerala, India. They are effective antioxidant and free radical scavenger under both in vitro and in vivo condition. The efficacy of the isolated flavonoids in conferring protection from radiation induced damages to genomic DNA was studied. Materials and Methods: The bioflavonoids, galangin and k...
متن کاملO-37: Pseudomalignant Nature of Placenta during Normal and Pathological Gestation Is Regulated by Epigenetic Mechanisms which Can be Exploited To Design Non-Invasive Fetal Dna Markers
Background Placentation shares many analogues with the development of tumors such as rapid proliferation, invasiveness, gene expression profiles especially the expression of tumor suppressor genes, oncogenes and matrixmetallo proteinases (MMPs). Thus, a placenta has been described as a pseudomalignant tissue. However, placentation is tightly regulated and any deregulation of this pseudomalignan...
متن کاملSperm DNA damage in mice irradiated with various doses of X-rays alone or in combination with actinomycin D or bleomycin sulfate: an in vivo study
Background: DNA damage in male germ cells due to exposure to environmental and manmade physico-chemical genotoxic agents is considered as the main cause of male infertility. The aim of this study was to evaluate the effects of combined modalities (radiotherapy and chemotherapy) routinely used for cancer treatment on mouse sperm chromatin in vivo. Materials and Methods: Forty-eight mice were div...
متن کامل