title: Maternal distress associates with placental genes regulating fetal glucocorticoid exposure and IGF2: Role of obesity and sex.
abstract: Maternal emotional distress symptoms, including life satisfaction, anxiety and depressed mood, are worse in Severely Obese (SO) than lean pregnancy and may alter placental genes regulating fetal glucocorticoid exposure and placental growth. We hypothesised that the associations between increased maternal distress symptoms and changes in placental gene expression including IGF2 and genes regulating fetal glucocorticoid exposure are more pronounced in SO pregnancy. We also considered whether there were sex-specific effects. Placental mRNA levels of 11β-HSDs, NR3C1-α, NR3C2, ABC transporters, mTOR and the IGF2 family were measured in term placental samples from 43 lean (BMI≤25kg/m(2)) and 50 SO (BMI≥40kg/m(2)) women, in whom distress symptoms were prospectively evaluated during pregnancy. The mRNA levels of genes with a similar role in regulating fetal glucocorticoid exposure were strongly inter-correlated. Increased maternal distress symptoms associated with increased NR3C2 and IGF2 isoform 1(IGF2-1) in both lean and SO group (p≤0.05). Increased distress was associated with higher ABCB1 and ABCG2 mRNA levels in SO but lower ABCB1 and higher 11β-HSD1 mRNA levels in lean (p≤0.05) suggesting a protective adaptive response in SO placentas. Increased maternal distress associated with reduced mRNA levels of ABCB1, ABCG2, 11β-HSD2, NR3C1-α and IGF2-1 in placentas of female but not male offspring. The observed sex differences in placental responses suggest greater vulnerability of female fetuses to maternal distress with potentially greater fetal glucocorticoid exposure and excess IGF2. Further studies are needed to replicate these findings and to test whether this translates to potentially greater negative outcomes of maternal distress in female offspring in early childhood.
authors.affiliation: University BHF Centre for Cardiovascular Sciences, Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland, UK; Tommy's Centre for Maternal and Fetal Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, Scotland, UK.
authors.forename: Theresia H
authors.initials: TH
authors.lastname: Mina
authors.affiliation: Institute of Behavioral Sciences, University of Helsinki, 00014 Helsinki, Finland.
authors.forename: Katri
authors.initials: K
authors.lastname: Räikkönen
authors.affiliation: MRC Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, Scotland, UK; Tommy's Centre for Maternal and Fetal Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, Scotland, UK.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Riley
authors.affiliation: MRC Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, Scotland, UK; Tommy's Centre for Maternal and Fetal Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, Scotland, UK.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Norman
authors.affiliation: University BHF Centre for Cardiovascular Sciences, Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland, UK; Tommy's Centre for Maternal and Fetal Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, Scotland, UK. Electronic address: r.reynolds@ed.ac.uk.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Reynolds
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D047109:Fetal Development / Q000502:physiology; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000378:metabolism; D008137:Longitudinal Studies; D008431:Maternal-Fetal Exchange / Q000502:physiology; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D010920:Placenta / Q000378:metabolism / Q000502:physiology*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012737:Sex Factors; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; C035170:IGF2 protein, human; D012333:RNA, Messenger; D007335:Insulin-Like Growth Factor II; D006854:Hydrocortisone
keywords: 11β-Dehydrogenase; ABC transporters; Anxiety; Depression; Glucocorticoids; IGF2; Life satisfaction; Obesity; Placenta; Pregnancy