Maternal distress associates with placental genes regulating fetal glucocorticoid exposure and IGF2: Role of obesity and sex
Open accessAbstract
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.
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Lower levels of mRNAs encoding key enzymes regulating glucocorticoid transfer, including 11β-HSD2, were found in female placentas from women suffering anxiety or depression compared to male counterparts.
“Similarly, lower levels of mRNAs encoding key enzymes regulating glucocorticoid transfer, including 11ß-HSD2, were found in female placentas from women suffering anxiety or depression compared to male counterparts (381).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [381]
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- Authors
- Mina, T. H., Räikkönen, K., Riley, S. C., Norman, J. E., & Reynolds, R. M.
- Affiliations
- The Queen's Medical Research Institute (GB)
- University of Helsinki (FI)
- MRC Centre for Reproductive Health (GB)
- Corresponding author
- Reynolds, Rebecca M.
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 59
- Pages
- 112-122
- ISSN
- 0306-4530 (ISSN-L)
- OpenAlex
- W1942198132
- Cited by
- 76
- References
- 55
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 3 · 2023: 8 · 2022: 10 · 2021: 5 · 2020: 8 · 2019: 8 · 2018: 16 · 2017: 9 · 2016: 2
- FWCI
- 9.64
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by-nc-nd)
- Bristol Research (University of Bristol) (submittedVersion)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Keywords
- maternal distress, maternal obesity, placental gene expression, fetal glucocorticoid exposure, 11β-hydroxysteroid dehydrogenase type 1, 11β-hydroxysteroid dehydrogenase type 2, P-glycoprotein, ABCG2, mineralocorticoid receptor, mTOR, sex differences, pregnancy, life satisfaction, anxiety, depressive mood
- MeSH terms
- Adult, Female, Gene Expression Regulation, Glucocorticoids, Humans, Hydrocortisone, Insulin-Like Growth Factor II, Longitudinal Studies, Maternal-Fetal Exchange, Obesity, Placenta, Pregnancy, Pregnancy Complications, RNA, Messenger, Sex Factors, Stress, Psychological, Case-Control Studies, Fetal Development
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