ArticleHistochemistry and cell biology2026
Gestational stage-related changes in hepatic Nrf1 and Nrf2 immunoreactivity in mid to late rat pregnancy.
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Abstract
Pregnancy induces marked metabolic and physiological adaptations in the maternal liver to maintain systemic homeostasis and support fetal development. Nuclear factor erythroid 2-related factors 1 and 2 (Nrf1 and Nrf2) are Cap'n'Collar (CNC) transcription factors that regulate antioxidant response element (ARE)-dependent gene expression and play essential roles in redox homeostasis and cellular stress responses; however, their gestational stage-dependent intracellular distribution in the maternal liver remains insufficiently characterized. This study investigated the immunohistochemical expression and subcellular localization of Nrf1 and Nrf2 in the maternal rat liver during mid and late gestation. Liver samples were obtained from non-pregnant control rats and pregnant Wistar albino rats on gestational days (GD) 13, 18, and 20 (n = 6 per group). Immunohistochemistry was performed using anti-Nrf1 and anti-Nrf2 antibodies, and staining intensities in nuclear and cytoplasmic compartments were quantified using Fiji (ImageJ). Nuclear-to-cytoplasmic (N/C) ratios were also calculated. Nrf1 immunoreactivity showed gestational stage-dependent changes, with stronger nuclear and cytoplasmic staining at GD13 and reduced staining at GD18 and GD20, accompanied by lower N/C ratios during mid gestation. In contrast, Nrf2 nuclear immunoreactivity remained relatively stable throughout most of gestation, with a significant decrease observed only between GD18 and GD20, whereas cytoplasmic immunoreactivity increased at GD13 and GD18 and declined at GD20. Statistical analysis demonstrated significant gestational stage-related differences in nuclear immunoreactivity, cytoplasmic immunoreactivity, and the N/C ratio for Nrf1. For Nrf2, significant differences were also observed in nuclear immunoreactivity, cytoplasmic immunoreactivity, and the N/C ratio, although pairwise differences in nuclear immunoreactivity were limited to GD18 and GD20. These findings demonstrate distinct gestational stage-dependent patterns of Nrf1 and Nrf2 immunoreactivity in the maternal liver, suggesting differential involvement of these transcription factors in maternal hepatic adaptation during pregnancy.
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