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Co‐expression of placental RAGE and g‐H2AX during intrauterine growth restriction and preeclampsia in rodents
Author(s) -
Tsai K.Y.F.,
Hirschi-Budge K. M.,
Davis T.,
Llavina S.,
Fowers R.,
Reynolds Paul R.,
Arroyo J.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.04261
Subject(s) - placenta , dna damage , preeclampsia , fetus , intrauterine growth restriction , medicine , histone , andrology , endocrinology , proteinuria , receptor , biology , dna , pregnancy , genetics , kidney
Intrauterine growth restriction (IUGR) and preeclampsia (PE) are obstetrics complications associated with poor outcomes for the both the mother and fetus. Although both characteristically differ, both diseases are associated with placental malfunction that stems in part from increased placental apoptosis. DNA double strand breaks (DNA‐DSBs) represent some of the most destructive forms of genomic damage in which both strands of DNA are ruptured. H2AX is a component of the histone octomer and is phosphorylated to form g‐H2AX in response to the sensing of DNA‐DSBs. The receptor for advanced glycation end‐products (RAGE) is a multi‐ligand receptor primarily expressed on cell membranes, where it functions as a progression factor in inflammatory signaling; however, the nuclear isoform of RAGE (nRAGE) has been described as having a crucial role in DNA‐DSBs repair. The purpose of this study was to identify placental DNA damage, placental nRAGE and g‐H2AX expression in a secondhand smoke exposed rodent model of IUGR and a Gas6 induced PE model. Placental and fetal weights were determined at the time of necropsy in the IUGR model. Blood pressure and proteinuria was assessed in the PE model. Characterizing DNA degradation was used to confirm placental DNA damage during these pregnancy complications. Immunohistochemistry was used to determine localization of both molecules in the placenta. Relative to controls we observed: 1) decreased placental and fetal weights (1.4‐fold and 2.3‐fold; p<0.003) during IUGR; 2) significantly increased systolic and diastolic blood pressure and proteinuria (80%; p<0.05) during PE; 3) increased DNA degradation in the IUGR and PE placentas and 4) Increased staining for RAGE and g‐H2AX in the IUGR and PE placentas. These results may provide insight into the physiological relevance of these molecules, and if so, their modification during gestation may help alleviate placental disease. Support or Funding Information This work was supported by a grant from the Flight Attendant’s Medical Research Institute (FAMRI, PRR and JAA) and a BYU Mentoring Environment Grant (JAA and PRR).