Chiara Mandò

• PhD
• Professor (Associate) at University of Milan

The iron need in pregnancy is significantly higher in comparison to that in the nonpregnant state. The iron absorbed during pregnancy is used for expansion of the maternal erythrocyte mass, to fulfill the fetus's iron needs, to create placenta, and to cope with blood loss at delivery. Term neonates have a total body store of about 1 g of iron, all...

Periodontal disease (PD) during pregnancy may trigger systemic inflammation, increasing the risk of developing cardiometabolic disease (CMD). As a consequence, PD may result in the activation of cellular and molecular pathways, affecting the disease course and pregnancy outcome. Although microRNAs (miRNAs) are considered ideal biomarkers for many d...

Maternal obesity has been associated with short- and long-term risks of pregnancy-perinatal adverse events, possibly due to alterations of placental mitochondrial bioenergetics. However, several detrimental mechanisms occurring in the placentas of women with obesity still need to be clarified. Here, we analyzed placental mitochondrial features and...

Inflamm-aging refers to the chronic low-grade inflammation that occurs with aging and cellular senescence, and it is linked to various diseases. Understanding the markers involved in inflammation and aging, as well as their interaction with environmental factors and bodily control mechanisms, can provide crucial tools for assessing the resilience (...

Background: Inflamm-aging refers to the chronic low-grade inflammation that occurs with aging and cellular senescence, and it is linked to various diseases. Understanding the markers involved in inflammation and aging, as well as their interaction with environmental factors and bodily control mechanisms, can provide crucial tools for assessing the...

Background High-resolution respirometry (HRR) of human biopsies can provide useful metabolic, diagnostic, and mechanistic insights for clinical research and comparative medical studies. Fresh tissues analysis offers the potential best condition, the drawback being the need to use them shortly after dissection for mitochondrial respiratory experimen...

Maternal obesity (MO) is expanding worldwide, contributing to the onset of Gestational Diabetes Mellitus (GDM). MO and GDM are associated with adverse maternal and foetal outcomes, with short- and long-term complications. Growing evidence suggests that MO and GDM are characterized by epigenetic alterations contributing to the pathogenesis of metabo...

Introduction: Monochorionic twins (MC) develop under unique intrauterine conditions and show a high risk of compromise during fetal life. Here we describe umbilical vein blood flow (UVBF) and fetal oxygen and glucose utilization in uncomplicated MC twins and investigate possible differences within twin-pairs according to birth-order. Methods: Pr...

Maternal obesity is associated with inflammation and oxidative stress, strongly impacting the intrauterine environment with detrimental consequences for both mother and offspring. The saliva is a non-invasive biofluid reflecting both local and systemic health status. This observational study aimed to profile the epigenetic signature in the saliva o...

Alterations in intrauterine fetal growth increase the risk of adverse perinatal and neonatal outcomes. In this retrospective study, we analyzed data of 906 pregnancies collected in our maternal fetal medicine center, with different patterns of growth: 655 AGA (Appropriate for Gestational Age), 62 SGA (Small for Gestational Age: fetuses born with a...

Background: Nutritional quality during pregnancy is crucial for mother and child health and their short/long-term outcomes. The aim of this study is to evaluate the adherence to nutritional recommendations in Italy during the three pregnancy trimesters in Normal Weight (NW) and Over Weight (OW) women. Methods: Data from a multicenter randomized...

During female lifetime and pregnancy, inflammation and cellular senescence are implicated in physiological processes, from ovulation and menstruation, to placental homeostasis and delivery. Several lifestyles, nutritional, and environmental insults, as well as long-lasting pregestational inflammatory diseases may lead to detrimental effects in prom...

SARS-CoV-2 infection has been related to adverse pregnancy outcomes. A placental role in protecting the fetus from SARS-CoV-2 infection has been documented. Nevertheless, it is still unclear how the placenta is affected in SARS-CoV-2 infection. Here we assessed placental mitochondrial (mt) and oxidative features in COVID-19 and healthy mothers. mtD...

Maternal obesity and gestational diabetes mellitus (GDM) are increasing worldwide, representing risk factors for both mother and child short/long-term outcomes. Oxidative stress, lipotoxicity and altered autophagy have already been reported in obesity, but few studies have focused on obese pregnant women with GDM. Antioxidant and macro/chaperone-me...

Introduction Maternal pregestational obesity is a significant risk factor for adverse pregnancy outcomes, such as gestational diabetes. Both these conditions can have an impact on placental development and affect maternal-fetal exchanges, compromising fetal metabolic status. The aim of the study is to investigate the influence of pre-pregnancy BMI...

Introduction Gestational diabetes mellitus (GDM) is the most frequent metabolic complication during pregnancy and is associated with development of short-term and long-term complications for newborns, with large-for-gestational-age (LGA) being particularly common. Interestingly, the mechanism behind altered fetal growth in GDM is only partially und...

Obesity is becoming pandemic and is associated with impaired reproductive potential. Oxidative stress, low-grade chronic inflammation and mitochondrial dysfunctions, which characterize obesity, strongly affect oocyte environment and function. Supplementation with antioxidant and anti-inflammatory compounds has been suggested to improve fertility. H...

Maternal dietary intake during pregnancy needs to meet increased nutritional demands to maintain metabolism and to support fetal development. Docosahexaenoic acid (DHA) is essential for fetal neuro-/visual development and in immunomodulation, accumulating rapidly within the developing brain and central nervous system. Levels available to the fetus...

In healthy pregnancy, glucose and oxygen availability are essential for fetal growth and well being. However, how substrate delivery and fetal uptake are affected in human pregnancy complicated by fetal growth restriction (FGR) is still unknown. Here, we show that the human FGR fetus has a strikingly reduced umbilical uptake of both oxygen and gluc...

Background: SSRIs (Selective Serotonin Reuptake Inhibitors) are the most useful drugs to treat depression during pregnancy. Intrauterine exposure to SSRIs may increase the risk of growth restriction, preterm birth and neonatal complications. However, advantages in treating depression seem to exceed potential drug side effects in respect un-treated...

Gestational diabetes mellitus (GDM) is the most frequent metabolic complication during pregnancy, affecting 3% to 25% women, and it is associated with abnormal fetal growth. Interestingly, the mechanism behind altered fetal growth in GDM is only partially understood. In order to discover novel factors that may play a role in placental function and...

Introduction: Sex steroids are regulating factors for intrauterine growth. 17-β Estradiol (E2) is particularly critical to a physiological pregnancy, as increased maternal E2 was correlated to lower fetal weight at delivery. The placenta itself is a primary source of estrogens, synthetized from cholesterol precursors. Cytochrome P450 aromatase (enc...

A lipotoxic placental environment is recognized in maternal obesity, with increased inflammation and oxidative stress. These changes might alter mitochondrial function, with excessive production of reactive oxygen species, in a vicious cycle leading to placental dysfunction and impaired pregnancy outcomes. Here, we hypothesize that maternal pregest...

Background: Maternal obesity is related to immunologic and inflammatory systemic modifications that may worsen the pregnancy inflammatory status. Hormonal changes during pregnancy can adversely affect oral biofilms and oral health initiating or worsening periodontal diseases, with enhanced local and systemic oxidative stress and inflammation. Obj...

Fetal growth restriction affects up to 10% of live-born infants representing a major cause of neonatal morbidity and mortality worldwide, being a significant risk factor for future adult health. A reduction of nutrient supply and oxygenation is the final common basis in fetal growth restriction. However, mechanisms involved can be various, and depe...

Introduction: Intrauterine growth restriction (IUGR) and preeclampsia (PE) are pregnancy disorders characterized by placental insufficiency with oxygen/nutrient restriction and oxidative stress, all influencing mitochondria functionality and number. Moreover, IUGR and PE fetuses are predisposed to diseases later in life, and this might occur throug...

OBJECTIVE: Maternal obesity is characterized by systemic low-grade inflammation and oxidative stress (OxS) with the contribution of fetal sex dimorphism. We recently described increased mitochondrial content (mtDNA) in placentas of obese pregnancies. Here we quantify mtDNA and hepcidin as indexes of OxS and systemic inflammation in the obese matern...

Introduction: Estrogen-Related Receptor gamma (ERRy) is an activator of mitochondrial (mt) biogenesis. Moreover, ERRy can affect the estrogen pathway by binding the Estrogen Receptor (ER) or modulating CYP19 expression, an aromatase involved in 17-Beta Estradiol (E2) production. During pregnancy, the fetus-placenta unit is the primary source of est...

Brief Introduction Maternal Obesity (MO) is due to a calories imbalance and incorrect dietary intake. Obesity results in chronic mild inflammation and oxidative stress. Moreover, MO exerts its influence on perinatal and childhood outcomes, related to maternal excessive Body Mass Index (BMI) and/or Gestational Weight Gain (GWG). Few studies investig...

During pregnancy, a well functioning placenta is needed to ensure appropriate growth and development of the fetus [1]. Indeed, a malfunctioning or “insufficient” placenta has been recognized as the “cause” of Intrauterine Growth Restriction (IUGR) [2], leading to decreased oxygen delivery as well as altered placental transport of nutrients, mainly...

Purpose: Iron supplementation is associated with side effects and overload risk. We compared different regimens of iron supplementation on maternal hematological status and pregnancy outcome in a cohort of healthy pregnant women. Materials and methods: Eighty non-anemic women with a normal singleton pregnancy were recruited at 11-13 weeks and ra...

Unlabelled: Human placental mesenchymal stromal cells (pMSCs) have never been investigated in intrauterine growth restriction (IUGR). We characterized cells isolated from placental membranes and the basal disc of six IUGR and five physiological placentas. Cell viability and proliferation were assessed every 7 days during a 6-week culture. Expressi...

Introduction: Placental biometry at birth has been shown to predict chronic disease in later life. We hypothesized that maternal overweight/obesity, a state of low-grade inflammation and risk factor for adverse pregnancy outcome, could negatively influence placental development and that differences would be sex-specific. Methods: 696 women (537...

Trophoblast expression of Human Leukocyte Antigene-G (HLA-G) is essential for feto-maternal immune tolerance and successful placentation. There is contradicting evidence on the relationship between HLA-G polymorphisms and preeclampsia (PE), intrauterine growth restriction (IUGR) and pregnancy-induced hypertension (PIH). Here, we investigate the ass...

Introduction: Obesity is associated with higher gestational risks leading to premature births (PB). Obesity is also an established risk factor for periodontal diseases (PD) and PD has been associated with PB and low birth weight. Here we report oral evaluation data of obese pregnant women (OB), as part of an ongoing observational study investigatin...

Introduction: Estrogen-Related Receptor gamma (ERRγ) is a transcriptional factor acting on mitochondrial (mt) biogenesis. It also can affect the estrogen pathway by binding the Estrogen Receptor or modulating Cytochrome P450-CYP19 expression, that is involved in estradiol production. We recently showed significantly lower ERRγ levels in cytotrophob...

Mitochondrial content in cytotrophoblast cells under hypoxic conditions Chiara Mandò, Gaia Maria Anelli, Chiara Novielli, Veronica Clivio, Irene Cetin University of Milan, Dept. Biomedical and Clinical Sciences L. Sacco, Milan, Italy; University of Milan, Center for Fetal Research Giorgio Pardi, Milan, Italy OBJECTIVES Intrauterine growth restric...

INTRODUCTION Nuclear Respiratory Factor 1 (NRF1), PPARg-coactivator 1α (PGC-1α) and Estrogen-Related Receptor γ (ERRγ) are important regulators of mitochondrial (mt) biogenesis, by controlling mtDNA transcription and activating nuclear genes involved in mt biogenesis. We previously showed higher mtDNA levels in placental tissue of intrauterine grow...

Intrauterine growth restriction (IUGR) and pregnancy hypertensive disorders such as preeclampsia (PE) associated with IUGR share a common placental phenotype called "placental insufficiency" originating in early gestation, when high availability of energy is required. Here, we assess mitochondrial content and the expression and activity of respirat...

Background: Amino acid placental delivery is reduced in human intrauterine growth-restricted (IUGR) fetuses, and the activity of placental amino transporters has been consistently shown to be decreased in in vitro studies. We hypothesized lower placental expression and localization of sodium-coupled neutral amino acid transporter 2 (SNAT2 (also kn...

Purpose of review: Intrauterine growth restriction (IUGR) occurs when fetal growth rate falls below the genetic potential and affects a significant number of pregnancies, but still no therapy has been developed for this pregnancy disease. This article reviews the most recent findings concerning maternal characteristics and behaviours predisposing...

Pregestational obesity is a significant risk factor for adverse pregnancy outcomes. Maternal obesity is associated with a specific proinflammatory, endocrine and metabolic phenotype that may lead to higher supply of nutrients to the feto-placental unit and to excessive fetal fat accumulation. In particular, obesity may influence placental fatty aci...

Early onset placenta Preeclampsia (ePE) with Intrauterine Growth Restriction (IUGR) is associated with insufficient placental function, leading to decreased nutrient and oxygen (O2) availability for the fetus [1]. Mitochondria (mt) are the cell energy producers. Mt dysfunctions could be involved in altered placental metabolism leading to ePE and IU...

IntroductionModels to study placental metabolism and transportStable isotope studies in human pregnanciesNon-steady-state or steady-state kineticsPlanning a study with stable isotopesBlood analysis of stable isotope enrichmentsAcknowledgmentReferences

We investigated mitochondrial DNA (mtDNA) content in the maternal circulation of normal pregnancies of different gestational ages and in pregnancies complicated by intrauterine growth restriction (IUGR). We examined 70 maternal blood samples: 13 nonpregnant women; 45 normal pregnancies, divided into the 3 trimesters; and 12 pregnancies complicated...

Iron (Fe) deficiency in pregnancy is associated to low birth weight and premature delivery while in adults it can result in increased blood pressure and cardiovascular disease. Cellular Fe uptake is mediated by the Transferrin Receptor 1 (TFRC), located in the trophoblast membranes. Here, we measured TFRC mRNA expression (Real Time PCR) and TFRC pr...

Intrauterine growth restriction (IUGR) depends on the placental capacity to transfer oxygen and nutrients from the maternal to the fetal circulation. Placental insufficiency may be caused by impairment of the maternal or fetal circulation by a thrombotic event, possibly associated with thrombophilic disorders. The goals of our study were to define...

Genomic imprinting, resulting in parent-of-origin-dependent gene expression, is mainly achieved by DNA methylation. IGF2 and H19, belonging to the same cluster of imprinted genes and regulated by ICR1, DMR2 and H19 promoter elements, play a major role in fetal/placental growth. Using quantitative approaches, we explored the epigenetic modulation of...

Genomic imprinting, resulting in parent-of-origin-dependent gene expression, is mainly achieved by DNA methylation. IGF2 and H19, belonging to the same cluster of imprinted genes and regulated by ICR1, DMR2 and H19 promoter elements, play a major role in fetal/placental growth. Using quantitative approaches, we explored the epigenetic modulation of...

The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and the Adducin-1 (ADD1) G460W nonsense single nucleotide polymorphism (SNP) have previously been associated to hypertension, whereas their association with preeclampsia (PE) and gestational hypertension (GH) is still controversial. We genotyped ACE I/D, ADD1 G460W, and A...