Gestation under chronic constant light leads to extensive gene expression changes in the fetal rat liver
Open accessAbstract
Recent reports account for altered metabolism in adult offspring from pregnancy subjected to abnormal photoperiod, suggesting fetal programming of liver physiology. To generate a pipeline of subsequent mechanistic experiments addressing strong candidate genes, here we investigated the effects of constant gestational light on the fetal liver transcriptome. At 10 days of gestation, dams were randomized in two groups ( n = 7 each): constant light (LL) and normal photoperiod (12 h light/12 h dark; LD). At 18 days of gestation, RNA was isolated from the fetal liver and subjected to DNA microarray (Affymetrix platform for 28,000 genes). Selected differential mRNAs were validated by quantitative PCR (qPCR), while integrated transcriptional changes were analyzed with Ingenuity Pathway Analysis and other bioinformatics tools. Comparison of LL relative to LD fetal liver led to the following findings. Significant differential expression was found for 3,431 transcripts (1,960 upregulated and 1,471 downregulated), with 393 of them displaying ≥ 1.5-fold change. We validated 27 selected transcripts by qPCR, which displayed fold-change values highly correlated with microarray ( r 2= 0.91). Different markers of nonalcoholic fatty liver disease were either upregulated (e.g., Ndn and Pnpla3) or downregulated (e.g., Gnmt, Bhmt1/2, Sult1a1, Mpo, and Mat1a). Diverse pathways were altered, including hematopoiesis, coagulation cascade, complement system, and carbohydrate and lipid metabolism. The microRNAs 7a-1, 431, 146a, and 153 were upregulated, while the abundant hepatic miRNA 122 was downregulated. Constant gestational light induced extensive modification of the fetal liver transcriptome. A number of differentially expressed transcripts belong to fundamental functional pathways, potentially contributing to long-term liver disease.
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Maternal circadian disruption alters offspring metabolic functioning in adulthood, including regulation of glucocorticoids and insulin.
“Likewise, maternal circadian disruption alters offspring metabolic functioning in adulthood13, 17–19, including the regulation of glucocorticoids17 and insulin18.”
From Maternal and Early-Life Circadian Disruption Have Long-Lasting Negative Consequences on Offspring Development and Adult Behavior in Mice (2017) · cites this paper as [13]
Exposing pregnant mice and rats to constant light produces lasting increases in anxiety-like behavior.
“In previous studies, exposing pregnant mice and rats to constant light produced lasting increases in anxiety-like behavior13–15, with mixed results in learning tasks14–16 and associated hippocampal functions15, 16.”
From Maternal and Early-Life Circadian Disruption Have Long-Lasting Negative Consequences on Offspring Development and Adult Behavior in Mice (2017) · cites this paper as [13]
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From the ruler to the smartphone tasks applied to identify sleep deprivation
Bellone, G. J., Fedele, M. M., Abulafia, C., Plano, S. A., Golombek, D. A., & Vigo, D. E. (2020) · Sleep Science · doi:10.5935/1984-0063.20200007
Trujillo, C., Miranda, F., & Sarmiento, J. (2026) · Clocks & Sleep · doi:10.3390/clockssleep8020035
- Authors
- Spichiger, C., Torres-Farfan, C., Galdames, H. A., Mendez, N., Alonso-Vazquez, P., & Richter, H. G.
- Affiliations
- Austral University of Chile (CL)
- Laboratory of Developmental Chronobiology, Institute of Anatomy, Histology and Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile
- Corresponding author
- Richter, Hans G.
- Venue
- Physiological Genomics
- Publisher
- American Physiological Society
- Published
- 2015-12
- Volume
- 47
- Issue
- 12
- Pages
- 621-633
- ISSN
- 1094-8341 (ISSN-L)
- 1531-2267
- OpenAlex
- W2469020469
- Cited by
- 34
- References
- 56
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 17 · 2019: 3 · 2018: 3 · 2017: 1 · 2016: 1
- FWCI
- 1.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Physiological Genomics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- continuous light exposure, fetal programming, photoperiod, non-alcoholic fatty liver disease, microRNA, hepatic gene expression, lipid metabolism, carbohydrate metabolism, hematopoiesis, coagulation, complement system, rats
- MeSH terms
- Animals, Female, Fetus, Gene Expression Regulation, Light, Liver, Liver Diseases, Pregnancy, Oligonucleotide Array Sequence Analysis, MicroRNAs, Lipid Metabolism, Rats
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