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Cited by 94Stress Responses and CortisolMaternal Mental Health During Pregnancy and PostpartumBirth, Development, and Health

Maternal stress, placental 11β-hydroxysteroid dehydrogenase type 2, and infant HPA axis development in humans: Psychosocial and physiological pathways

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Jahnke, Johanna R., Terán, Enrique, Murgueitio, Francisca, Cabrera, Holger, Thompson, Amanda L.·2021·Placenta
DOI 10.1016/j.placenta.2020.12.008PMC PMC7906936
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Abstract

Introduction Prenatal stress is known to influence fetal hypothalamic-pituitary-adrenal axis (HPA axis) development. Placental 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) is a central gene in this pathway, but little is known about what influences its functioning. We assess how maternal distress influences HSD11B2 functioning, and how HSD11B2 in turn, is associated with infant HPA axis development. Methods Data come from 24 mother-infant dyads on the Galápagos Islands. Using adjusted linear regression models, we assess the effects of maternal psychosocial (stress and depressive symptoms, measured by the Perceived Stress Scale and the Patient Health Questionnaire-8, respectively) and physiological (HPA axis dysregulation) distress during pregnancy on HSD11B2 methylation and expression and then test how these HSD11B2 measures influence infant HPA axis development. Results Maternal HPA axis dysregulation during pregnancy is associated with lower placental HSD11B2 expression, which is associated with an exaggerated cortisol reactivity in infants. Sex-specific analyses revealed that maternal depressive symptoms may influence the functioning of placental HSD11B2 differently in girls (n = 11, 46%) than in boys (n = 13, 54%), though the sample size was small. Discussion These results support a disrupted adaptive framework, in which the ability to upregulate HSD11B2 expression in response to acute stress diminishes as maternal stress becomes chronic. In this model, chronic stress may exhaust the protective mechanism of HSD11B2, leaving the infant vulnerable to high levels of maternal cortisol, which could injure the fetal HPA axis and disrupt long-term neurobehavioral and metabolic development. While larger studies will be needed to confirm these findings, this study offers exploratory results on the effects of maternal distress on both HSD11B2 methylation and expression and the effect of HSD11B2 on offspring HPA axis development.

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  • Variability in placental enzyme activity (e.g., 11β-HSD2 activity fluctuations causing 230% differences in GC exposure) further complicates dosing.

    “Variability in placental enzyme activity (e.g., 11β-HSD2 activity fluctuations causing 230% differences in GC exposure) further complicates dosing (13).”

    From Placenta-pulmonary coupling-guided multimodal AI for fetal lung maturity staging and individualized glucocorticoid therapy (2026) · cites this paper as [13]

    The Introduction says placental HSD11B2 buffers fetal glucocorticoid exposure, and the Results (Placental HSD11B2 characteristics) document variation in methylation and gene expression. The paper does not report 230% differences in exposure or assess whether enzyme variability complicates dosing; its measurements of expression should not be treated as measurements of enzyme activity. (LLM, conf=0.86)

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References 56 · Cited by 94

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Authors
Jahnke, J. R., Terán, E., Murgueitio, F., Cabrera, H., & Thompson, A. L.
Affiliations
  • Galapagos Science Center (EC)
  • Ministerio de Salud Pública (EC)
  • University of North Carolina at Chapel Hill (US)
ORCID
Venue
Placenta
Publisher
Elsevier BV
Published
2021-01
Volume
104
Pages
179-187
ISSN
0143-4004 (ISSN-L)
DOI
10.1016/j.placenta.2020.12.008
PMC
PMC7906936
OpenAlex
W3116512115
Cited by
94
References
56
Citations by year
2026: 28 · 2025: 20 · 2024: 13 · 2023: 13 · 2022: 13 · 2021: 7
FWCI
4.68
Type
journal article
Language
en
Open access
Licence
Locations
  • Placenta (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Science Foundation (BCS-1730297)
  • Graduate School, University of North Carolina at Chapel Hill
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32-HD007168)
  • University of North Carolina at Chapel Hill
  • Carolina Population Center, University of North Carolina at Chapel Hill
  • Fulbright Association
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • 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
Keywords
maternal stress, prenatal stress, 11β-hydroxysteroid dehydrogenase type 2, maternal depressive symptoms, cortisol response, DNA methylation, gene expression, sex differences, chronic stress, fetal programming, Galápagos Islands
MeSH terms
Adolescent, Adult, Female, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Infant, Pituitary-Adrenal System, Placenta, Pregnancy, Prenatal Exposure Delayed Effects, Saliva, Stress, Psychological, DNA Methylation, 11-beta-Hydroxysteroid Dehydrogenase Type 2, Young Adult

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