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Review
. 2019 Feb 15:7:337-360.
doi: 10.1146/annurev-animal-020518-115154. Epub 2018 Sep 7.

Prenatal Steroids and Metabolic Dysfunction: Lessons from Sheep

Affiliations
Review

Prenatal Steroids and Metabolic Dysfunction: Lessons from Sheep

Rodolfo C Cardoso et al. Annu Rev Anim Biosci. .

Abstract

Prenatal exposure to excess steroids or steroid mimics can disrupt the normal developmental trajectory of organ systems, culminating in adult disease. The metabolic system is particularly susceptible to the deleterious effects of prenatal steroid excess. Studies in sheep demonstrate that prenatal exposure to excess native steroids or endocrine-disrupting chemicals with steroidogenic activity, such as bisphenol A, results in postnatal development of numerous cardiometabolic perturbations, including insulin resistance, increased adiposity, altered adipocyte size and distribution, and hypertension. The similarities in the phenotypic outcomes programmed by these different prenatal insults suggest that common mechanisms may be involved, and these may include hormonal imbalances (e.g., hyperandrogenism and hyperinsulinemia), oxidative stress, inflammation, lipotoxicity, and epigenetic alterations. Animal models, including the sheep, provide mechanistic insight into the metabolic repercussions associated with prenatal steroid exposure and represent valuable research tools in understanding human health and disease. Focusing on the sheep model, this review summarizes the cardiometabolic perturbations programmed by prenatal exposure to different native steroids and steroid mimics and discusses the potential mechanisms underlying the development of adverse outcomes.

Keywords: cardiometabolic disease; developmental programming; sheep; steroid hormones.

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Figures

Figure 1
Figure 1
Schematic illustrating the effects of prenatal insults in programming adverse health outcomes in the offspring. Prenatal exposure to different insults during critical periods of fetal development results in physiological adaptations that often prove to be detrimental and result in failure to overcome programmed pathology. Abbreviation: EDC, endocrine-disrupting chemical.
Figure 2
Figure 2
Schematic model for developmental changes in insulin sensitivity in female sheep prenatally exposed to testosterone (T) excess. This working model is supported by findings of insulin resistance during early life in prenatal T-treated sheep, followed by elevated insulin sensitivity at postpubertal age, normal insulin sensitivity during early adulthood, and reestablishment of insulin resistance later in adult life. Collectively, observations in the ovine model are suggestive of the existence of a period of compensatory adaptation of the metabolic tissues to prenatal exposure to excess T.
Figure 3
Figure 3
Schematic illustrating the effects of prenatal exposure to steroid excess on cardiometabolic organ systems. Prenatal exposure to native steroids (e.g., androgens and glucocorticoids) or endocrine-disrupting chemicals (EDCs) with steroidogenic potential (e.g., bisphenol A) act via common mechanistic pathways to reprogram several organ systems in the offspring resulting in the development of adult cardiometabolic disease. Abbreviation: HPA, hypothalamic-pituitary-adrenal; HPG, hypothalamic-pituitary-gonadal; IGF1, insulin-like growth factor 1; IUGR, intrauterine growth restriction. Source of images used in this figure: https://pixabay.com..

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References

    1. Barker D 2004. The developmental origins of adult disease. J. Am. Coll. Nutr. 23:588S–95S - PubMed
    1. Fowden AL, Forhead AJ. 2004. Endocrine mechanisms of intrauterine programming. Reproduction 127:515–26 - PubMed
    1. Padmanabhan V, Cardoso RC, Puttabyatappa M. 2016. Developmental programming, a pathway to disease. Endocrinology 157:1328–40 - PMC - PubMed
    1. Hanson MA, Gluckman P. 2014. Early developmental conditioning of later health and disease: Physiology or pathophysiology? Physiol. Rev. 94:1027–76 - PMC - PubMed
    1. Barker DJ. 2007. The origins of the developmental origins theory. J. Intern. Med. 261:412–17 - PubMed

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