Maternal obesity and sex-specific differences in placental pathology

Leon-Garcia, Sandra; Roeder, Hilary; Nelson, Katelyn N.; Liao, Xiaoyan; Pizzo, Donald; Laurent, Louise C.; Parast, Mana M.; LaCoursiere, D. Yvette

doi:10.1016/j.placenta.2015.12.006

Cited by 95 publications

(71 citation statements)

References 29 publications

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“…; Leon‐Garcia et al . ). In addition, maternal diet or stress has been shown to induce male‐specific placental inflammation in rodent models (Bronson & Bale ; Reynolds et al .…”

Section: Discussionmentioning

confidence: 97%

“…Consistent with previous reports from human placentas, the most interesting finding in our study is that multiple genes related to inflammation and immune response are expressed higher in males and are more induced by Dex in a male-specific manner. Importantly, substantial evidence has been accumulated to demonstrate the effect of fetal sex on placental inflammation and sex-specific differences in placental pathology, with a variety conditions such as maternal obesity, preterm delivery, PE and IUGR (Ghidini & Salafia 2005;Walker et al 2012;Leon-Garcia et al 2016). In addition, maternal diet or stress has been shown to induce male-specific placental inflammation in rodent models (Bronson & Bale 2014;Reynolds et al 2015).…”

Section: Discussionmentioning

confidence: 99%

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Prenatal exposure to dexamethasone in the mouse induces sex‐specific differences in placental gene expression

et al. 2017

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Prenatal stress during pregnancy leads to sex-specific effects on fetal development and disease susceptibility over the life span; however, the origin of sex differences has not been identified. The placenta not only plays a key role in fetal growth and development throughout pregnancy, but also affects the fetal programming underlying subsequent adult health and accounts. Therefore, sex-specific adaptation of the placenta may be central to the sex differences in fetal growth and survival. Here, we analyzed the effects of prenatal dexamethasone (Dex) on sex-specific changes in placental gene expression using RNA-Seq. Placental tissues from males and females were separated into two developmentally distinct fetal and maternal parts at E11.5 stage. The majority of genes in female placentas were downregulated by prenatal Dex, whereas those were mostly maintained or rather upregulated in male placentas. RNA-Seq results were validated using independent biological replicates from the same stage and placental tissue samples from E18.5 by realtime PCR assays. Activation of various inflammatory response-related genes, chemokines and their receptors, particularly in male placentas, strongly implies that prenatal Dex exposure causes sex-specific physiological responses that can lead to inflammatory diseases involving vascular pathology.

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“…; Leon‐Garcia et al . ). In addition, maternal diet or stress has been shown to induce male‐specific placental inflammation in rodent models (Bronson & Bale ; Reynolds et al .…”

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Prenatal exposure to dexamethasone in the mouse induces sex‐specific differences in placental gene expression

et al. 2017

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“…Hypoxia has been shown to directly increase lipid accumulation in human trophoblasts23, therefore it may also contribute to the increased placental lipid accumulation. Other factors that may contribute to a hypoxic state include inflammation2425 and mitochondrial dysfunction26 which are observed preferentially in female placentae, while other factors such as oxidative stress27 and ER stress28 appear to be sex-independent.…”

Section: Discussionmentioning

confidence: 99%

Exercise rescues obese mothers’ insulin sensitivity, placental hypoxia and male offspring insulin sensitivity

Fernandez‐Twinn

Gascoin

Musiał

et al. 2017

Sci Rep

109

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The prevalence of obesity during pregnancy continues to increase at alarming rates. This is concerning as in addition to immediate impacts on maternal wellbeing, obesity during pregnancy has detrimental effects on the long-term health of the offspring through non-genetic mechanisms. A major knowledge gap limiting our capacity to develop intervention strategies is the lack of understanding of the factors in the obese mother that mediate these epigenetic effects on the offspring. We used a mouse model of maternal-diet induced obesity to define predictive correlations between maternal factors and offspring insulin resistance. Maternal hyperinsulinemia (independent of maternal body weight and composition) strongly associated with offspring insulin resistance. To test causality, we implemented an exercise intervention that improved maternal insulin sensitivity without changing maternal body weight or composition. This maternal intervention prevented excess placental lipid deposition and hypoxia (independent of sex) and insulin resistance in male offspring. We conclude that hyperinsulinemia is a key programming factor and therefore an important interventional target during obese pregnancy, and propose moderate exercise as a promising strategy to improve metabolic outcome in both the obese mother and her offspring.

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“…In the current study, blood levels of galectin‐9, but not sPD‐L1, were significantly higher in pregnancies with male fetuses compared to females. Studies of the placenta indicated that inflammation was more common in obese mothers with female fetuses compared to male fetuses . Systemically, male fetuses induce a more inflammatory state in the maternal blood during pregnancy than females .…”

Section: Discussionmentioning

confidence: 99%

Immune checkpoint molecules soluble program death ligand 1 and galectin‐9 are increased in pregnancy

Enninga

Harrington

Creedon

et al. 2017

American J Rep Immunol

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ProblemPregnancy requires balance between tolerance to the haploidentical fetus and the mother's ability to mount immune responses. There are parallels to this phenomenon that occur in metastatic cancer. We assessed soluble program death ligand‐1 soluble PD‐L1 (sPD‐L1) and galectin‐9 in the blood of pregnant women during gestation as these molecules are highly involved in immune suppression during cancer.Method of studyMaternal blood was collected from 30 primigravida women at monthly intervals during pregnancy, delivery and 6‐week post‐partum. Blood was analyzed for sPD‐L1 and galectin‐9 concentrations by ELISA. Term placentas were collected in formalin and IHC was completed for PD‐L1 and galectin‐9 expression.ResultsMaternal blood levels of sPD‐L1 (0.438 ng/mL) and galectin‐9 (1976 pg/mL) were elevated early in normal pregnancies compared to non‐pregnant controls (0.242 ng/mL and 773 pg/mL, respectively). sPD‐L1 increased throughout gestation, whereas galectin‐9 remained elevated until parturition; both proteins returned to control levels post‐partum. Women carrying male fetuses had significantly higher galectin‐9 levels, but not sPD‐L1, than those carrying females (2263 pg/mL vs 1874 pg/mL; P = .0005). Trophoblast cells of the term placenta coexpress galectin‐9 and PD‐L1.ConclusionImmune‐regulatory molecules galectin‐9 and sPD‐L1 increased during pregnancy and may play a role in immune tolerance that is critical for the fetus.

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Maternal obesity and sex-specific differences in placental pathology

Cited by 95 publications

References 29 publications

Prenatal exposure to dexamethasone in the mouse induces sex‐specific differences in placental gene expression

Prenatal exposure to dexamethasone in the mouse induces sex‐specific differences in placental gene expression

Exercise rescues obese mothers’ insulin sensitivity, placental hypoxia and male offspring insulin sensitivity

Immune checkpoint molecules soluble program death ligand 1 and galectin‐9 are increased in pregnancy

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