Adding robustness to rigor and reproducibility for the three Rs of improving translational medical research

McGill, Michael P.; Threadgill, David W.

doi:10.1172/jci173750

Cited by 4 publications

(2 citation statements)

References 26 publications

(17 reference statements)

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“…tpsDig2w64 ( Rohlf, 2005 ) then adds additional landmarks, including the midpoints between features and other aspects of the outline, producing a total of 47 landmarks. As we did not anticipate that the Low-exposure treatment would impact craniofacial development, we collected additional Control and Low samples in a separate experimental cohort to ensure the reproducibility and robustness of our data ( von Kortzfleisch et al, 2020 ; McGill and Threadgill, 2023 ).…”

Section: Methodsmentioning

confidence: 99%

Chronic paternal alcohol exposures induce dose-dependent changes in offspring craniofacial shape and symmetry

Higgins,

Bhadsavle,

Gaytan

et al. 2024

Front. Cell Dev. Biol.

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Although dose-response analyses are a fundamental tool in developmental toxicology, few studies have examined the impacts of toxicant dose on the non-genetic paternal inheritance of offspring disease and dysgenesis. In this study, we used geometric morphometric analyses to examine the impacts of different levels of preconception paternal alcohol exposure on offspring craniofacial shape and symmetry in a mouse model. Procrustes ANOVA followed by canonical variant analysis of geometric facial relationships revealed that Low-, Medium-, and High-dose treatments each induced distinct changes in craniofacial shape and symmetry. Our analyses identified a dose threshold between 1.543 and 2.321 g/kg/day. Below this threshold, preconception paternal alcohol exposure induced changes in facial shape, including a right shift in facial features. In contrast, above this threshold, paternal exposures caused shifts in both shape and center, disrupting facial symmetry. Consistent with previous clinical studies, changes in craniofacial shape predominantly mapped to regions in the lower portion of the face, including the mandible (lower jaw) and maxilla (upper jaw). Notably, high-dose exposures also impacted the positioning of the right eye. Our studies reveal that paternal alcohol use may be an unrecognized factor contributing to the incidence and severity of alcohol-related craniofacial defects, complicating diagnostics of fetal alcohol spectrum disorders.

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Section: Methodsmentioning

confidence: 99%

Chronic paternal alcohol exposures induce dose-dependent changes in offspring craniofacial shape and symmetry

Higgins,

Bhadsavle,

Gaytan

et al. 2024

Front. Cell Dev. Biol.

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“…Like humans, foals exhibit wide genetic variation, enabling clinical researchers to examine a diverse range of patient immunological responses and disease severity in an outbred population ( 35 ). Consequently, the foal model represents a powerful tool for studying the role of innate immunity in immune responses to vaccines in neonates.…”

Section: Introductionmentioning

confidence: 99%

Enteral immunization with live bacteria reprograms innate immune cells and protects neonatal foals from pneumonia

da Silveira,

Kahn,

Legere

et al. 2024

Preprint

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Neonatal immunization faces several challenges due to the immune system's immaturity and naivety, and several vaccines that induce adequate immune response in adults fail to protect neonates. Using a horse foal model, we show that enteral administration of Rhodococcus equi to newborn foals overcomes neonatal vaccination challenges by reprogramming innate immune responses, inducing R. equi-specific adaptive humoral and cell-mediated immune responses and protecting foals against experimental pneumonia challenge. Immunized foals exhibit changes in the epigenetic profile of blood monocytes, >1,000 differentially-expressed genes in neutrophils, and higher levels of R. equi-specific IgG1, IgG4/7, and T helper type 1 response. Together, our data indicate that early life exposure to R. equi in the gastrointestinal tract can induce enhanced innate immune responses, which may facilitate the development of adaptive immune responses and protect neonates against pneumonia through a previously unappreciated gut-lung axis.

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Maternal 129S1/SvImJ background attenuates the placental phenotypes induced by chronic paternal alcohol exposure

Bhadsavle,

Scaturro,

Golding

2024

Reproductive Toxicology

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Adding robustness to rigor and reproducibility for the three Rs of improving translational medical research

Cited by 4 publications

References 26 publications

Chronic paternal alcohol exposures induce dose-dependent changes in offspring craniofacial shape and symmetry

Chronic paternal alcohol exposures induce dose-dependent changes in offspring craniofacial shape and symmetry

Enteral immunization with live bacteria reprograms innate immune cells and protects neonatal foals from pneumonia

Maternal 129S1/SvImJ background attenuates the placental phenotypes induced by chronic paternal alcohol exposure

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