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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-mediated autophagy (CMA)-related gene expressions were evaluated herein in obese and GDM placentas. A total of 47 women with singleton pregnancies delivered by elective cesarean section were enrolled: 16 normal weight (NW), 18 obese with no comorbidities (OB GDM(-)), 13 obese with GDM (OB GDM(+)). Placental gene expression was assessed by real-time PCR. Antioxidant gene expression ( CAT , GPX1 , GSS ) decreased, the pro-autophagic ULK1 gene increased and the chaperone-mediated autophagy regulator PHLPP1 decreased in OB GDM(-) vs. NW. On the other hand, PHLPP1 expression increased in OB GDM(+) vs. OB GDM(-). When analyzing results in relation to fetal sex, we found sexual dimorphism for both antioxidant and CMA-related gene expressions. These preliminary results can pave the way for further analyses aimed at elucidating the placental autophagy role in metabolic pregnancy disorders and its potential targetability for the treatment of diabetes outcomes. more...

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 on placental size and to evaluate the role of obesity and gestational diabetes mellitus (GDM) on fetal oxygenation in overweight and obese pregnant women., Methods: 208 normal weight (NW), 57 overweight (OW) and 69 obese (OB) women were studied at elective cesarean section (CS) at term. 10 OW and 24 OB women were affected by GDM. Maternal, fetal and placental data were collected. Respiratory gases and acid-base balance were measured in umbilical venous and arterial blood., Results: Placental weight and thickness were higher in OB pregnancies. Lower fetal-placental ratios (F/P) were found in GDM pregnancies, both OW and OB. Fetuses from OB mothers were more hypoxic and acidemic compared to NW, particularly when complicated by GDM., Discussion: In agreement with previous studies, our data show that placentas from OB and GDM pregnancies are heavier and thicker, suggesting that an unbalanced pregestational nutritional status can decrease the placental efficiency in maternal-fetal exchanges. Fetuses from obese women are also hypoxic and acidemic, while fetuses from gestational diabetic mothers are hypoxic, reflecting that an altered pre-pregnancy BMI can affect fetal oxygenation, and GDM can play an additional detrimental role, thus worsening placental function and fetal oxygenation., (Copyright © 2020 Elsevier Ltd. All rights reserved.) more...

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 understood., Research Design and Methods: A proteomic approach was used to analyze placental samples obtained from healthy pregnant women (n=5), patients with GDM (n=12) and with GDM and LGA (n=5). Effects of altered proteins on fetal development were tested in vitro in human embryonic stem cells (hESCs)., Results: Here, we demonstrate that the placental proteome is altered in pregnant women affected by GDM with LGA, with at least 37 proteins differentially expressed to a higher degree (p<0.05) as compared with those with GDM but without LGA. Among these proteins, 10 are involved in regulating tissue differentiation and/or fetal growth and development, with bone marrow proteoglycan (PRG2) and dipeptidyl peptidase-4 (DPP-4) being highly expressed. Both PRG2 and DPP-4 altered the transcriptome profile of stem cells differentiation markers when tested in vitro in hESCs, suggesting a potential role in the onset of fetal abnormalities., Conclusions: Our findings suggest that placental dysfunction may be directly responsible for abnormal fetal growth/development during GDM. Once established on a larger population, inhibitors of the pathways involving those altered factors may be tested in conditions such as GDM and LGA, in which therapeutic approaches are still lacking., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.) more...

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., Objective: The aim of this study was to examine the relationship between local salivary and systemic parameters of oxidative stress and inflammation in relation to obesity and periodontal diseases., Study Design: Sixty-two women with singleton pregnancies were enrolled. Twenty-seven women were normal weight (NW; 18.5< body mass index [BMI] <25 kg/m 2 ) and 35 obese (BMI ≥30 kg/m 2 ). Seventeen of the obese had gestational diabetes mellitus (GDM). During third trimester, periodontal status was evaluated, saliva (s) was collected to assess total antioxidant capacity (s-TAC) and C-reactive protein (s-CRP) levels, and venous plasma (p) was used to measure CRP levels (p-CRP). Maternal, fetal, and placental data were registered at delivery., Results: Levels of s-TAC, s-CRP, and p-CRP were significantly higher in obese, particularly in the presence of GDM, compared to NW and related to each other ( P = .000; r > 0.59), to maternal BMI ( P = .000; r > 0.52), and fasting glycemia ( P < .002; r > 0.47). Periodontal disease was more frequent in obese groups (80%) versus NW (52%; P = .04), particularly when GDM was diagnosed ( P = .009). A significant interaction effect between maternal BMI and oral condition was found for s-TAC levels. Obese with periodontitis showed significant increase in local and systemic parameters versus NW., Conclusion: Obesity and periodontal disease could synergistically amplify the inflammatory and oxidative status, resulting in increased local and systemic biomarkers particularly when GDM is diagnosed. more...