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1.
Placenta ; 113: 57-66, 2021 09 15.
Article in English | MEDLINE | ID: mdl-34053733

ABSTRACT

Preeclampsia is a pregnancy-specific syndrome characterized by a sudden increase in blood pressure accompanied by proteinuria and/or maternal multi-system damage associated to poor fetal outcome. In early-onset preeclampsia, utero-placental perfusion is altered, causing constant and progressive damage to the syncytiotrophoblast, generating syncytiotrophoblast stress. The latter leads to the detachment and release of syncytiotrophoblast fragments, anti-angiogenic factors and pro-inflammatory molecules into maternal circulation, resulting in the emergence and persistence of the characteristic symptoms of this syndrome during pregnancy. Therefore, understanding the origin and consequences of syncytiotrophoblast stress in preeclampsia is vital to develop new therapeutic alternatives, focused on reducing the burden of this syndrome. In this review, we describe five central characteristics of syncytial stress that should be targeted or prevented in order to reduce preeclampsia symptoms: histological alterations, syncytiotrophoblast damage, antiangiogenic protein export, placental deportation, and altered syncytiotrophoblast turnover. Therapeutic management of these characteristics may improve maternal and fetal outcomes.


Subject(s)
Pre-Eclampsia/physiopathology , Stress, Physiological , Trophoblasts/physiology , Animals , Female , Humans , Pre-Eclampsia/etiology , Pregnancy
2.
Expert Rev Clin Pharmacol ; 13(3): 247-263, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32129110

ABSTRACT

Introduction: The placenta is a temporary and unique organ that allows for the physical connection between a mother and fetus; this organ regulates the transport of gases and nutrients mediating the elimination of waste products contained in the fetal circulation. The placenta performs metabolic and excretion functions, on the basis of multiple enzymatic systems responsible for the oxidation, reduction, hydrolysis, and conjugation of xenobiotics. These mechanisms give the placenta a protective role that limits the fetal exposure to harmful compounds. During pregnancy, some diseases require uninterrupted treatment even if it is detrimental to the fetus. Drugs and other xenobiotics alter gene expression in the placenta with repercussions for the fetus and mother's well-being.Areas covered: This review provides a brief description of the human placental structure and function, the main drug and xenobiotic transporters and metabolizing enzymes, placenta-metabolized substrates, and alterations in gene expression that the exposure to xenobiotics may cause.Expert opinion: Research should be focused on the identification and validation of biological markers for the assessment of the harmful effects of some drugs in pregnancy, including the evaluation of polymorphisms and methylation patterns in chorionic villous samples and/or amniotic fluid.


Subject(s)
Maternal-Fetal Exchange/physiology , Placenta/metabolism , Xenobiotics/pharmacokinetics , Animals , Female , Fetus/physiology , Gene Expression Regulation/drug effects , Humans , Placenta/enzymology , Pregnancy , Xenobiotics/adverse effects
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