Age-related oxidative modifications to uterine albumin impair extravillous trophoblast cells function.

Abstract Advanced maternal age is associated not only with a significant reduction in fertility but also with an additional risk of developing pregnancy-related disorders. Most of these disorders are now believed to be the clinical manifestation of an incorrect placentation, namely deficient transformation of maternal spiral arteries and ineffective trophoblast invasion through uterine stroma. In the present study it was hypothesized that an age-related loss in uterine redox homeostasis interferes with the function of extravillous trophoblasts (EVTs) and placentation. To test this hypothesis, relative levels of oxidatively modified proteins were evaluated in human samples from placenta and placental bed, and the role of specific oxidative modifications to proteins in placentation was studied using a cell culture model of EVTs. In the placental bed, the carbonylation level of a 66 kDa protein (identified as albumin) presented a strong, positive and significant correlation with maternal age. Albumin was immunodetected preferentially in endothelial cells and connective tissue between muscle fascicles. In vitro results showed that carbonylated albumin overload did not alter cell viability, but reduced EVTs motility and triggered cell stress response pathways. Moreover, EVTs presented decreased ability to adhere to and invade a collagen extracellular matrix pre-treated with carbonylated albumin. In conclusion, reproductive ageing is accompanied by an increase in maternal uterine carbonylated albumin, that may have a deleterious role in the modulation of EVTs function.