Placental pathology and fetal growth outcomes in pregnancies complicated by maternal obesity

Hietalati, Samantha; Pham, Donna; Arora, Harneet; Mochizuki, Marina; Santiago, Gisselle; Vaught, Jordan; Lin, Erika T.; Mestan, Karen K.; Parast, Mana; Jacobs, Marni B.

doi:10.1038/s41366-024-01546-y

Cited by 3 publications

References 45 publications

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Maternal obesogenic diet disrupts mid-gestation decidual immune and vascular homeostasis without impairing spiral artery remodelling

Bellissimo,

Yeo,

Ribeiro

et al. 2024

Preprint

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Excess maternal adiposity (i.e., overweight and obesity) during pregnancy has been linked to impaired uteroplacental perfusion, compromised placental development, and a higher risk of adverse pregnancy outcomes. Owing to the nature of chronic inflammation and immune dysregulation accompanying excess adiposity, disruption of leukocyte-mediated tissue remodelling and immunoregulation within the decidua have emerged as likely drivers contributing to suboptimal placental function in pregnancies impacted by maternal overweight or obesity. However, the impacts of excess adiposity on major populations of innate lymphoid cells (ILCs) and macrophages which orchestrate these processes and the environment that these cells occupy remain vastly understudied. Here, we used a mouse model of chronic high-fat, high-sucrose (HFHS) diet-feeding to characterize the impacts of an obesogenic milieu on decidual immune dynamics during placental development at mid-gestation (E10.5). HFHS pregnancies exhibited marked increases in total decidual leukocyte abundance, driven by population-level increases in tissue-resident and conventional NK cells, and MHC-II+ macrophages. This was not associated with abnormalities in implantation site morphology or decidual spiral artery remodelling but was coincident with histological patterns of local inflammation. In line with this, expression of canonical proinflammatory cytokines and chemokines were moderately upregulated in bulk decidual tissue of HFHS dams. This was accompanied by more potent elevations in multiple mediators of angiogenesis, endothelial activation, and coagulation in HFHS decidual tissue. Collectively, these findings point towards pathological vascular inflammation and possibly dysregulated decidual angiogenesis in the first half of pregnancy as factors predisposing to reduced placental efficiency, malperfusion, and inflammation seen in pregnancies affected by maternal overweight and obesity.

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Maternal obesogenic diet disrupts mid-gestation decidual immune and vascular homeostasis without impairing spiral artery remodelling

Bellissimo,

Yeo,

Ribeiro

et al. 2024

Preprint

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Maternal diet during pregnancy and adaptive changes in the maternal and fetal pancreas have implications for future metabolic health

Hill,

Hill

2024

Front. Endocrinol.

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Fetal and neonatal development is a critical period for the establishment of the future metabolic health and disease risk of an individual. Both maternal undernutrition and overnutrition can result in abnormal fetal organ development resulting in inappropriate birth size, child and adult obesity, and increased risk of Type 2 diabetes and cardiovascular diseases. Inappropriate adaptive changes to the maternal pancreas, placental function, and the development of the fetal pancreas in response to nutritional stress during pregnancy are major contributors to a risk trajectory in the offspring. This interconnected maternal-placental-fetal metabolic axis is driven by endocrine signals in response to the availability of nutritional metabolites and can result in cellular stress and premature aging in fetal tissues and the inappropriate expression of key genes involved in metabolic control as a result of long-lasting epigenetic changes. Such changes result is insufficient pancreatic beta-cell mass and function, reduced insulin sensitivity in target tissues such as liver and white adipose and altered development of hypothalamic satiety centres and in basal glucocorticoid levels. Whilst interventions in the obese mother such as dieting and increased exercise, or treatment with insulin or metformin in mothers who develop gestational diabetes, can improve metabolic control and reduce the risk of a large-for-gestational age infant, their effectiveness in changing the adverse metabolic trajectory in the child is as yet unclear.

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Placental Bioenergetics and Antioxidant Homeostasis in Maternal Obesity and Gestational Diabetes

Mandò,

Castiglioni,

Novielli

et al. 2024

Antioxidants

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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 oxidative environment of 46 pregnancies in relation to pre-pregnancy BMI. Seventeen Caucasian normal-weight (NW) and twenty-nine women who were obese (OB) were enrolled. The protein expression of mitochondrial CypD and electron transfer chain complexes (C) I–V were measured, as well as ATP production and oxygen consumption rates (OCRs). The protein levels of the pro/anti-oxidant enzymes TXNIP, SOD2, and PON2 were also analyzed. Despite no differences in CypD expression, OCRs were significantly lower in OB vs. NW women. Accordingly, ATP synthase (CV) levels and ATP content were decreased in OB women, positively correlating with placental efficiency, suggesting a link between ATP deficiency and placental dysfunction. SOD2 expression negatively correlated with maternal BMI, indicating a possible impairment of antioxidant defenses with increasing BMI. These changes were worsened in 10 OB women presenting with gestational diabetes mellitus. Overall, these results suggest alterations of placental bioenergetics in pregnancies of women with obesity, possibly leading to placental dysfunction and altered fetal development and programming.

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Placental pathology and fetal growth outcomes in pregnancies complicated by maternal obesity

Cited by 3 publications

References 45 publications

Maternal obesogenic diet disrupts mid-gestation decidual immune and vascular homeostasis without impairing spiral artery remodelling

Maternal obesogenic diet disrupts mid-gestation decidual immune and vascular homeostasis without impairing spiral artery remodelling

Maternal diet during pregnancy and adaptive changes in the maternal and fetal pancreas have implications for future metabolic health

Placental Bioenergetics and Antioxidant Homeostasis in Maternal Obesity and Gestational Diabetes

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