Leptin is differentially expressed and epigenetically regulated across monochorionic twin placenta with discordant fetal growth
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Notice bibliographique
Résumé
Severely growth-discordant monochorionic (MC) twins offer a unique opportunity to study fetal and placental growth based on a similar genetic background and maternal host environment where the healthy twin serves as an ideal control. Differences in development of MC twins may therefore be due to differential epigenetic regulation of genes involved in placental development and function. Growth-discordant twins are known for abnormal angio-architecture in the placenta of the smaller twin. Since the reasons for this phenotype are mostly unknown this study was aimed to investigate the expression and regulation of genes known to be involved in angiogenesis. We studied 10 severely growth-discordant MC twin placentas (birthweight difference ≥20%) without twin-twin-transfusion syndrome and 5 growth-concordant MC twin placentas. Growth-discordant twin placentas were phenotyped by histology. Placental mRNA expression of 88 angiogenesis-related genes was measured by PCR array. ELISA assay and immunohistochemistry were used to confirm PCR results. EpiTYPTER for DNA methylation was used to determine if methylation ratios were responsible for differential gene expression. The PCR array analysis showed significant mRNA up-regulation in the placental share of the smaller twin for several genes. These included leptin (24.6-fold, P = 0.017), fms-like tyrosine kinase 1 (Flt1, 2.4-fold, P = 0.016) and Endoglin (Eng, 1.86-fold, P = 0.078). None of the other 84 angiogenesis-related genes showed significant differences. ELISA confirmed significantly increased leptin protein expression (49.22 versus 11.03 pg/ml, P = 0.049) in the smaller twin of the discordant growth cohort. Leptin expression in smaller twins' placentas was associated with elevated DNA methylation of the leptin promotor region suggesting the inhibition of binding of a transcriptional activator/inhibitor in that region. We attempted to overcome the limitation of sample size by careful patient selection. We minimized any bias in placental sampling by random sampling from two different sites and by avoiding sampling from areas with grossly visible abnormalities using a standardized sampling protocol. In conclusion, the smaller twin's placenta is characterized by differentially increased gene expressions for Flt1 and Eng mRNA that may be causally associated with the villous pathology driven by abnormal feto-placental angiogenesis. The substantial up-regulation of leptin mRNA may be epigenetically conferred and relevant to the post-natal risk of metabolic syndrome in intrauterine growth restriction offspring with placental pathology. Growth-discordant MC twins offer unique insights into the epigenetic basis of perinatal programming.
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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découle