The Role of Annexin A1 in DNA Damage Response in Placental Cells: Impact on Gestational Diabetes Mellitus

Abstract

The functions of annexin A1 (ANXA1), which is expressed on membranes and in cytoplasmic granules, have been fully described. Nonetheless, the role of this protein in protecting against DNA damage in the nucleus is still emerging and requires further investigation. Here, we investigated the involvement of ANXA1 in the DNA damage response in placental cells. Placenta was collected from ANXA1 knockout mice (AnxA1−/−) and pregnant women with gestational diabetes mellitus (GDM). The placental morphology and ANXA1 expression, which are related to the modulation of cellular response markers in the presence of DNA damage, were analyzed. The total area of AnxA1−/− placenta was smaller due to a reduced labyrinth zone, enhanced DNA damage, and impaired base excision repair (BER) enzymes, which resulted in the induction of apoptosis in the labyrinthine and junctional layers. The placentas of pregnant women with GDM showed reduced expression of AnxA1 in the villous compartment, increased DNA damage, apoptosis, and a reduction of enzymes involved in the BER pathway. Our translational data provide valuable insights into the possible involvement of ANXA1 in the response of placental cells to oxidative DNA damage and represent an advancement in investigations into the mechanisms involved in placental biology.

Urinary Metabolites of Polycyclic Aromatic Hydrocarbons of Rural Population in Northwestern China: Oxidative Stress and Health Risk Assessment

“…The urinary 8-OHdG levels of rural residents in the current study (median/GM: 3.79/4.07 ng mL –1 ) are similar to those of healthy individuals (median: 3.65 ng mL –1 ) but slightly higher than those of healthy incinerator workers (median: 2.28 ng mL –1 ) and lower than those of pregnant women undergoing metabolic changes (median/GM: 9.96/8.87 ng mL –1 ) . A higher level of oxidative DNA damage in pregnant women might be associated with the breakdown of syncytiotrophoblast during gestation in pregnancy. , The level of oxidative DNA damage in the Jingyuan population is at a normal level in comparison to other studies of healthy individuals. , The urinary concentration of diY (39.6 ng mL –1 ), an indicator of protein oxidative damage, of rural residents in Jingyuan is higher than that of residents living in nonindustrial contaminated areas, as reported in another study (median: 35.1 ng mL –1 ) . The urinary concentration of MDA in this study (2.28 nmol mL –1 ) is lower than that of some patients (e.g., early diabetic nephropathy subjects). , The comparison of OSBs indicates that DNA, RNA, and lipid expression in Jingyuan rural people are at a normal metabolic level, but there may be increased oxidative damage to proteins.…”

“…63 A higher level of oxidative DNA damage in pregnant women might be associated with the breakdown of syncytiotrophoblast during gestation in pregnancy. 64,65 The level of oxidative DNA damage in the Jingyuan population is at a normal level in comparison to other studies of healthy individuals. 11,66 The urinary concentration of diY (39.6 ng mL −1 ), an indicator of protein oxidative damage, of rural residents in Jingyuan is higher than that of residents living in nonindustrial contaminated areas, as reported in another study (median: 35.1 ng mL −1 ).…”