Transgenerational developmental programming

Aiken, Catherine; Ozanne, Susan E.

doi:10.1093/humupd/dmt043

Cited by 244 publications

(202 citation statements)

References 136 publications

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“…Epigenetic inheritance is frequently touted as the mechanism by which traits acquired in one generation are passed onto the next (for a review, see Grossniklaus et al 2013;Aiken and Ozanne 2014). Jirtle and Skinner (2007) explained that for epigenetic modifications to chromatin to be considered a plausible mechanism for inheritance of phenotypic change, then effects need to persist to at least the F 3 generation.…”

Section: Inter(trans)generational Inheritancementioning

confidence: 99%

Epigenetics and developmental programming of welfare and production traits in farm animals

Sinclair

Rutherford

Wallace

et al. 2016

Reprod. Fertil. Dev.

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Abstract. The concept that postnatal health and development can be influenced by events that occur in utero originated from epidemiological studies in humans supported by numerous mechanistic (including epigenetic) studies in a variety of model species. Referred to as the 'developmental origins of health and disease' or 'DOHaD' hypothesis, the primary focus of large-animal studies until quite recently had been biomedical. Attention has since turned towards traits of commercial importance in farm animals. Herein we review the evidence that prenatal risk factors, including suboptimal parental nutrition, gestational stress, exposure to environmental chemicals and advanced breeding technologies, can determine traits such as postnatal growth, feed efficiency, milk yield, carcass composition, animal welfare and reproductive potential. We consider the role of epigenetic and cytoplasmic mechanisms of inheritance, and discuss implications for livestock production and future research endeavours. We conclude that although the concept is proven for several traits, issues relating to effect size, and hence commercial importance, remain. Studies have also invariably been conducted under controlled experimental conditions, frequently assessing single risk factors, thereby limiting their translational value for livestock production. We propose concerted international research efforts that consider multiple, concurrent stressors to better represent effects of contemporary animal production systems.

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Section: Inter(trans)generational Inheritancementioning

confidence: 99%

Epigenetics and developmental programming of welfare and production traits in farm animals

Sinclair

Rutherford

Wallace

et al. 2016

Reprod. Fertil. Dev.

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“…adult Leydig stem/progenitor cells | compensated Leydig cell failure | GATA4 | ethane dimethane sulfonate E vidence that altered fetal growth/development can fundamentally alter the risk of health disorders in adulthood and perhaps, future generations continues to grow (1). Such fetal programming applies to common disorders encapsulated in the metabolic syndrome (2), which are interlinked in adult men with low testosterone levels (3).…”

mentioning

confidence: 99%

Fetal programming of adult Leydig cell function by androgenic effects on stem/progenitor cells

Kilcoyne

Smith

Atanassova

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

160

135

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Fetal growth plays a role in programming of adult cardiometabolic disorders, which in men, are associated with lowered testosterone levels. Fetal growth and fetal androgen exposure can also predetermine testosterone levels in men, although how is unknown, because the adult Leydig cells (ALCs) that produce testosterone do not differentiate until puberty. To explain this conundrum, we hypothesized that stem cells for ALCs must be present in the fetal testis and might be susceptible to programming by fetal androgen exposure during masculinization. To address this hypothesis, we used ALC ablation/regeneration to identify that, in rats, ALCs derive from stem/progenitor cells that express chicken ovalbumin upstream promoter transcription factor II. These stem cells are abundant in the fetal testis of humans and rodents, and lineage tracing in mice shows that they develop into ALCs. The stem cells also express androgen receptors (ARs). Reduction in fetal androgen action through AR KO in mice or dibutyl phthalate (DBP) -induced reduction in intratesticular testosterone in rats reduced ALC stem cell number by ∼40% at birth to adulthood and induced compensated ALC failure (low/normal testosterone and elevated luteinizing hormone). In DBP-exposed males, this failure was probably explained by reduced testicular steroidogenic acute regulatory protein expression, which is associated with increased histone methylation (H3K27me3) in the proximal promoter. Accordingly, ALCs and ALC stem cells immunoexpressed increased H3K27me3, a change that was also evident in ALC stem cells in fetal testes. These studies highlight how a key component of male reproductive development can fundamentally reprogram adult hormone production (through an epigenetic change), which might affect lifetime disease risk.adult Leydig stem/progenitor cells | compensated Leydig cell failure | GATA4 | ethane dimethane sulfonate

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“…Indeed, macrosomia itself is associated with an increased risk of developing obesity and metabolic syndrome (39) which appears to persist for multiple generations (40). Finally, all cause mortality has been shown to be increased in offspring of obese mothers (BMI > 30) compared with mothers with normal BMI (after adjustment for confounding variables; hazard ratio 1.35, 95% CI 1.17-1.55) (41).…”

Section: Impacts Of Maternal Obesity: Overview Of Epidemiologic Studiesmentioning

confidence: 99%

Of the bugs that shape us: maternal obesity, the gut microbiome, and long-term disease risk

2014

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Chronic disease risk is inextricably linked to our early-life environment, where maternal, fetal, and childhood factors predict disease risk later in life. Currently, maternal obesity is a key predictor of childhood obesity and metabolic complications in adulthood. Although the mechanisms are unclear, new and emerging evidence points to our microbiome, where the bacterial composition of the gut modulates the weight gain and altered metabolism that drives obesity. Over the course of pregnancy, maternal bacterial load increases, and gut bacterial diversity changes and is influenced by pre-pregnancy-and pregnancy-related obesity. Alterations in the bacterial composition of the mother have been shown to affect the development and function of the gastrointestinal tract of her offspring. How these microbial shifts influence the maternal-fetal-infant relationship is a topic of hot debate. This paper will review the evidence linking nutrition, maternal obesity, the maternal gut microbiome, and fetal gut development, bringing together clinical observations in humans and experimental data from targeted animal models.

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Transgenerational developmental programming

Cited by 244 publications

References 136 publications

Epigenetics and developmental programming of welfare and production traits in farm animals

Epigenetics and developmental programming of welfare and production traits in farm animals

Fetal programming of adult Leydig cell function by androgenic effects on stem/progenitor cells

Of the bugs that shape us: maternal obesity, the gut microbiome, and long-term disease risk

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