Intrauterine growth restriction: Clinical consequences on health and disease at adulthood.

Intrauterine growth restriction (IUGR) affects 10-15% of all pregnancies worldwide. IUGR may result from maternal, placental or fetal origin. Maternal malnutrition before and during pregnancy represents the most prevalent non-genetic or placental cause. IUGR reflects an abnormal adaptive fetal growth in a deleterious environment. Individuals born after IUGR are more susceptible to develop diseases related to subsequent stressors through a lifetime. Animal models help to decipher the underlying causes of dysregulated pathways and molecular modifications conditioning health and disease in adult offspring born after IUGR. The aim of this review is to summarize current knowledge on long term consequences of IUGR, integrating animal models and human studies for a better care of IUGR-born individuals in a life course perspective.

Effect of early postnatal nutrition on chronic kidney disease and arterial hypertension in adulthood: a narrative review.

Intrauterine growth restriction (IUGR) has been identified as a risk factor for adult chronic kidney disease (CKD), including hypertension (HTN). Accelerated postnatal catch-up growth superimposed to IUGR has been shown to further increase the risk of CKD and HTN. Although the impact of excessive postnatal growth without previous IUGR is less clear, excessive postnatal overfeeding in experimental animals shows a strong impact on the risk of CKD and HTN in adulthood. On the other hand, food restriction in the postnatal period seems to have a protective effect on CKD programming. All these effects are mediated at least partially by the activation of the renin-angiotensin system, leptin and neuropeptide Y (NPY) signaling and profibrotic pathways. Early nutrition, especially in the postnatal period has a significant impact on the risk of CKD and HTN at adulthood and should receive specific attention in the prevention of CKD and HTN.

At the heart of programming: the role of micro-RNAs.

Epidemiological and experimental observations tend to prove that environment, lifestyle or nutritional challenges influence heart functions together with genetic factors. Furthermore, when occurring during sensitive windows of heart development, these environmental challenges can induce an 'altered programming' of heart development and shape the future heart disease risk. In the etiology of heart diseases driven by environmental challenges, epigenetics has been highlighted as an underlying mechanism, constituting a bridge between environment and heart health. In particular, micro-RNAs which are involved in each step of heart development and functions seem to play a crucial role in the unfavorable programming of heart diseases. This review describes the latest advances in micro-RNA research in heart diseases driven by early exposure to challenges and discusses the use of micro-RNAs as potential targets in the reversal of the pathophysiology.

Transient postnatal over nutrition induces long-term alterations in cardiac NLRP3-inflammasome pathway.

BACKGROUND AND AIMS: The prevalence of obesity is increasing worldwide at an alarming rate. Altered early nutrition, in particular postnatal overfeeding (PNOF), is a risk factor for impaired cardiac function in adulthood. In the understanding of the initiation or progression of heart diseases, NLRP3 inflammasome and non-coding RNAs have been proposed as key players. In this context, the aim of this study was to decipher the role of NLRP3 inflammasome and its post transcriptional control by micro-RNAs in the regulation of cardiac metabolic function induced by PNOF in mice. METHODS AND RESULTS: Based on a model of mice exposed to PNOF through litter size reduction, we observed increased cardiac protein expression levels of NLRP3 and ETS-1 associated with alterations in insulin signaling. Additionally, miR-193b levels were down-regulated in the adult hearts of overfed animals. In a cardiomyocyte cell line, transfection with miR-193b induced down-regulation of ETS-1 and NLRP3 and improved insulin signaling. CONCLUSIONS: These findings suggest that the miR-193b could be involved in cardiac phenotypic changes observed in adulthood induced by PNOF likely through the regulation of ETS-1 and NLRP3 expression, and through this of insulin signaling.

Endothelial dysfunction in individuals born after fetal growth restriction: cardiovascular and renal consequences and preventive approaches.

Individuals born after intrauterine growth restriction (IUGR) have an increased risk of perinatal morbidity/mortality, and those who survive face long-term consequences such as cardiovascular-related diseases, including systemic hypertension, atherosclerosis, coronary heart disease and chronic kidney disease. In addition to the demonstrated long-term effects of decreased nephron endowment and hyperactivity of the hypothalamic-pituitary-adrenal axis, individuals born after IUGR also exhibit early alterations in vascular structure and function, which have been identified as key factors of the development of cardiovascular-related diseases. The endothelium plays a major role in maintaining vascular function and homeostasis. Therefore, it is not surprising that impaired endothelial function can lead to the long-term development of vascular-related diseases. Endothelial dysfunction, particularly impaired endothelium-dependent vasodilation and vascular remodeling, involves decreased nitric oxide (NO) bioavailability, impaired endothelial NO synthase functionality, increased oxidative stress, endothelial progenitor cells dysfunction and accelerated vascular senescence. Preventive approaches such as breastfeeding, supplementation with folate, vitamins, antioxidants, L-citrulline, L-arginine and treatment with NO modulators represent promising strategies for improving endothelial function, mitigating long-term outcomes and possibly preventing IUGR of vascular origin. Moreover, the identification of early biomarkers of endothelial dysfunction, especially epigenetic biomarkers, could allow early screening and follow-up of individuals at risk of developing cardiovascular and renal diseases, thus contributing to the development of preventive and therapeutic strategies to avert the long-term effects of endothelial dysfunction in infants born after IUGR.

The offspring of the diabetic mother--short- and long-term implications.

In the 1980s, David Barker and Colleagues proposed that the major causes of cardiovascular and metabolic diseases have their roots in early development. There is now robust evidence that an hyperglycemic intrauterine environment is responsible not only for significant short-term morbidity in the fetus and the neonate but also for an increased risk of developing diabetes as well as other chronic, noncommunicable diseases at adulthood. The risk is higher in pregestational diabetes, but unrecognized and/or poorly managed gestational diabetes (GDM) may have similar consequences. Although a relatively clear picture of the pathogenesis of the fetal and neonatal complications of maternal diabetes and of their interrelationship is available today, the intimate molecular mechanisms involved in the long term are far from being understood. While the rate of GDM is sharply increasing in association with the pandemic of obesity and of type 2 diabetes over the world, we review here the current understanding of short- and long-term outcomes of fetuses exposed to a diabetic environment.

[Long-term effects of environmental endocrine disruptors on male fertility]. / Effets à long terme des perturbateurs endocriniens environnementaux sur la fertilité masculine.

Several epidemiologic studies have demonstrated during the last 50 years an increased incidence in testis cancer, male genital tract malformations (cryptorchidism and hypospadias) and a decrease in sperm quality in men. These three pathologies seem to be linked and to belong to the testicular dysgenesis syndrome (TDS). It was suggested that TDS is a consequence of intra-uterine exposure to environmental compounds that disrupt the metabolism of native hormones. Such substances are so called endocrine disruptors (EDs). EDs are present in our daily environment such as food and water (through the use of pesticides), cosmetics, house-care products etc. Experimental models have been carried out to (i) establish a link between EDs exposure and SDT and (ii) identify the mechanisms that are involved in. After a brief definition of EDs and having underlined the importance of the window of exposure to EDs, several mechanisms will be described such as (i) intergenerational transmission (epigenetic), (ii) programmed cell death of testicular cells, (iii) modification of the androgenic signal and (iv) role of the germ cells-nourishing cells. To conclude, we will try to propose some biomarkers that would be useful to identify the potential link between fetal exposure to anti-androgenic EDs and male testicular pathology.