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Despite the widespread use of oxytocin for induction of labor, mechanistic insights into fetal/neonatal wellbeing are lacking because of the absence of an animal model that recapitulates modern obstetric practice. Here, we create and validate a hi-fidelity pregnant rat model that mirrors labor induction with oxytocin in laboring women. The model consists of an implantable preprogrammed microprocessor-controlled infusion pump that delivers a gradually escalating dose of intravenous oxytocin to induce birth at term gestation. We validated the model with molecular biological experiments on the uterine myometrium and telemetry-supported assessment of changes in intrauterine pressure. Finally, we applied this model to test the hypothesis that labor induction with oxytocin would be associated with oxidative stress in the newborn brain. Analysis of biomarkers of oxidative stress and changes in the expression of associated genes were no different between oxytocin-exposed and saline-treated pups, suggesting that oxytocin-induced labor was not associated with oxidative stress in the developing brain. Collectively, we provide a viable and realistic animal model for labor induction and augmentation with oxytocin that would enable new lines of investigation related to the impact of perinatal oxytocin exposure on the mother-infant dyad., (© 2022. The Author(s).)

The mammalian eye lens expresses a high concentration of crystallins (α, β and γ-crystallins) to maintain the refractive index essential for lens transparency. Crystallins are long-lived proteins that do not turnover throughout life. The structural destabilization of crystallins by UV exposure, glycation, oxidative stress and mutations in crystallin genes leads to protein aggregation and development of cataracts. Several destabilizing mutations in crystallin genes are linked with human autosomal dominant hereditary cataracts. To investigate the mechanism by which the α-crystallin mutations Cryaa-R49C and Cryab-R120G lead to cataract formation, we determined whether these mutations cause an altered expression of specific transcripts in the lens at an early postnatal age by RNA-seq analysis. Using knock-in mouse models previously generated in our laboratory, in the present work, we identified genes that exhibited altered abundance in the mutant lenses, including decreased transcripts for Clic5, an intracellular water channel in Cryaa-R49C heterozygous mutant lenses, and increased transcripts for Eno1b in Cryab-R120G heterozygous mutant lenses. In addition, RNA-seq analysis revealed increased histones H2B, H2A, and H4 gene expression in Cryaa-R49C mutant lenses, suggesting that the αA-crystallin mutation regulates histone expression via a transcriptional mechanism. Additionally, these studies confirmed the increased expression of histones H2B, H2A, and H4 by proteomic analysis of Cryaa-R49C knock-in and Cryaa;Cryab gene knockout lenses reported previously. Taken together, these findings offer additional insight into the early transcriptional changes caused by Cryaa and Cryab mutations associated with autosomal dominant human cataracts, and indicate that the transcript levels of certain genes are affected by the expression of mutant α-crystallin in vivo. [ABSTRACT FROM AUTHOR]

Correction to: I Scientific Reports i https://doi.org/10.1038/s41598-022-07236-x, published online 24 February 2022 The HTML version of the original version of this Article contained an error in the legend of Figure 4, where a portion of the text was incorrectly split and captured as an image credit. The original article can be found online at https://doi.org/10.1038/s41598-022-07236-x. [Extracted from the article]