Prenatal cytokine exposure results in obesity and gender-specific programming
Abstract
Prenatal events appear to program hormonal homeostasis, contributing to the development of somatic disorders at an adult age. The aim of this study was to examine whether maternal exposure to cytokines or to dexamethasone (Dxm) would be followed by hormonal consequences in the offspring at adult age. Pregnant rats were injected on days 8, 10, and 12 of gestation with either human interleukin-6 (IL-6) or tumor necrosis factor-α (TNF-α) or with Dxm. Control dams were injected with vehicle. All exposed offspring developed increased body weight ( P < 0.05–0.001), apparently due to an increase of 30–40% in adipose tissue weight ( P < 0.05–0.01). Corticosterone response to stress was increased in the IL-6 group ( P < 0.05–0.01). Dxm-treated male rats exhibited blunted Dexamethasone suppression test results. In male rats, insulin sensitivity was decreased after IL-6 exposure ( P < 0.01), whereas basal insulin was elevated in the TNF-α group ( P < 0.01). In female rats, plasma testosterone levels were higher in all exposed groups compared with controls ( P < 0.01–0.001), with the exception of Dxm-exposed offspring. Males in the TNF-α group showed decreased locomotor activity ( P < 0.05), and females in the IL-6 group showed increased locomotor activity ( P < 0.05). These results indicate that prenatal exposure to cytokines or Dxm leads to increased fat depots in both genders. In females, cytokine exposure was followed by a state of hyperandrogenicity. The results suggest that prenatal exposure to cytokines or Dxm can induce gender-specific programming of neuroendocrine regulation with consequences in adult life.
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In animal studies, excess glucocorticoid exposure in utero consistently programmes the offspring for increased adiposity.
“In animal studies, excess glucocorticoid exposure in utero was consistently shown to programme the offspring for increased adiposity (Table 6 and [119–123]).”
From Developmental programming of offspring adipose tissue biology and obesity risk (2021) · cites this paper as [122]
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Developmental programming of offspring adipose tissue biology and obesity risk
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- Authors
- Dahlgren, J., Nilsson, C., Jennische, E., Ho, H.-P., Eriksson, E., Niklasson, A., Björntorp, P., Wikland, K. A., & Holmäng, A.
- Affiliations
- Göteborg Pediatric Growth Research Center, Institute for the Health of Women and Children and Departments of
- University of Gothenburg (SE)
- Histology, and
- Pharmacology, and the
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2001-08-01
- Volume
- 281
- Issue
- 2
- Pages
- E326-E334
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2286769663
- Cited by
- 172
- References
- 7
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2022: 4 · 2021: 3 · 2020: 8 · 2019: 5 · 2018: 5 · 2017: 10 · 2016: 6 · 2015: 8 · 2014: 13 · 2013: 12 · 2012: 12
- FWCI
- 5.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 28997)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- interleukin-6, TNF-α, dexamethasone, developmental programming, obesity, adipose tissue, insulin sensitivity, hyperandrogenism, testosterone, locomotor activity, sex differences, neuroendocrine regulation, maternal immune activation
- MeSH terms
- Adipose Tissue, Animals, Body Weight, Corticosterone, Dexamethasone, Drug Administration Schedule, Exercise Test, Female, Glucocorticoids, Insulin, Male, Motor Activity, Neurosecretory Systems, Obesity, Pregnancy, Prenatal Exposure Delayed Effects, Sex Factors, Testosterone, Tumor Necrosis Factor-alpha, Interleukin-6, Cytokines, Rats
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