Programmed Adult Kidney Disease: Importance of Fetal Environment

Argeri, Rogério; Thomazini, Fernanda; Lichtenecker, Débora Conte Kimura; Thieme, Karina; Franco, Maria do Carmo; Gomes, Guiomar Nascimento

doi:10.3389/fphys.2020.586290

Cited by 6 publications

(4 citation statements)

References 101 publications

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“…Our team previously reported that IUH could result in long-lasting damage in the brain of offspring ( 1 ). Increasing evidence validated the theory of fetal origins of adult disease and that development of cardiovascular disease in adulthood might be associated with intrauterine insults ( 2 – 4 ). A study in rats revealed that antenatal hypoxia could also increase the severity of heart damage after ischemia-reperfusion injury in offspring ( 5 ).…”

Section: Introductionmentioning

confidence: 87%

Effects of Excessive Activation of N-methyl-D-aspartic Acid Receptors in Neonatal Cardiac Mitochondrial Dysfunction Induced by Intrauterine Hypoxia

Liu

Luo

Liao

et al. 2022

Front. Cardiovasc. Med.

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Intrauterine hypoxia is a common complication during pregnancy and could increase the risk of cardiovascular disease in offspring. However, the underlying mechanism is controversial. Memantine, an NMDA receptor antagonist, is reported to be a potential cardio-protective agent. We hypothesized that antenatal memantine treatment could prevent heart injury in neonatal offspring exposed to intrauterine hypoxia. Pregnant rats were exposed to gestational hypoxia or antenatal memantine treatment during late pregnancy. Newborns were then sacrificed to assess multiple parameters. The results revealed that Intrauterine hypoxia resulted in declining birth weight, heart weight, and an abnormally high heart weight/birth weight ratio. Furthermore, intrauterine hypoxia caused mitochondrial structural, functional abnormalities and decreased expression of DRP1, and upregulation of NMDAR1 in vivo. Antenatal memantine treatment,an NMDARs antagonist, improved these changes. In vitro, hypoxia increased the glutamate concentration and expression of NMDAR1. NMDAR activation may lead to similar changes in mitochondrial function, structure, and downregulation of DRP1 in vitro. Pharmacological blockade of NMDARs by the non-competitive NMDA antagonist MK-801 or knockdown of the glutamate receptor NR1 significantly attenuated the increased mitochondrial reactive oxygen species and calcium overload-induced by hypoxia exposure. These facts suggest that memantine could provide a novel and promising treatment for clinical use in intrauterine hypoxia during pregnancy to protect the cardiac mitochondrial function in the offspring. To our best knowledge, our research is the first study that shows intrauterine hypoxia can excessively activate cardiac NMDARs and thus cause mitochondrial dysfunction.

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Section: Introductionmentioning

confidence: 87%

Effects of Excessive Activation of N-methyl-D-aspartic Acid Receptors in Neonatal Cardiac Mitochondrial Dysfunction Induced by Intrauterine Hypoxia

Liu

Luo

Liao

et al. 2022

Front. Cardiovasc. Med.

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“…It is hypothesized that these adaptations are made in an attempt to confer the offspring with a selective advantage in the anticipated postnatal environment [ 4 ]. Studies have shown that a range of fetal and neonatal adaptations are made in response to such factors, resulting in physiological manifestations such as reduced muscle fiber and cardiomyocyte proliferation [ 5 ], reduced pancreatic β-cell proliferation [ 6 ] and reduced kidney nephron deposition [ 7 ]. Whereas these in utero adaptations may confer on the offspring the opportunity of reaching sexual maturity and passing on their own genes to the next generation, their long-term consequences increase an individual’s predisposition toward adult ill health.…”

Section: Introductionmentioning

confidence: 99%

Parental Programming of Offspring Health: The Intricate Interplay between Diet, Environment, Reproduction and Development

et al. 2022

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As adults, our health can be influenced by a range of lifestyle and environmental factors, increasing the risk for developing a series of non-communicable diseases such as type 2 diabetes, heart disease and obesity. Over the past few decades, our understanding of how our adult health can be shaped by events occurring before birth has developed into a well-supported concept, the Developmental Origins of Health and Disease (DOHaD). Supported by epidemiological data and experimental studies, specific mechanisms have been defined linking environmental perturbations, disrupted fetal and neonatal development and adult ill-health. Originally, such studies focused on the significance of poor maternal health during pregnancy. However, the role of the father in directing the development and well-being of his offspring has come into recent focus. Whereas these studies identify the individual role of each parent in shaping the long-term health of their offspring, few studies have explored the combined influences of both parents on offspring well-being. Such understanding is necessary as parental influences on offspring development extend beyond the direct genetic contributions from the sperm and oocyte. This article reviews our current understanding of the parental contribution to offspring health, exploring some of the mechanisms linking parental well-being with gamete quality, embryo development and offspring health.

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“…54 More recent studies have confirmed previous data regarding the role of an adverse fetal environment on kidney maldevelopment, leading to changes in renal phenotypes, with consequences on renal structure and metabolism, including modifications in the renal-angiotensin system and its components. 55…”

Section: Fetal Programming Of Kidney Diseasesmentioning

confidence: 99%

The fascinating theory of fetal programming of adult diseases: A review of the fundamentals of the Barker hypothesis

Faa,

Fanos,

Manchia

et al. 2024

Journal of Public Health Research

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The theory of fetal programming of adult diseases was first proposed by David J.P. Barker in the eighties of the previous century, to explain the higher susceptibility of some people toward the development of ischemic heart disease. According to his hypothesis, poor maternal living conditions during gestation represent an important risk factor for the onset of atherosclerotic heart disease later in life. The analysis of the early phases of fetal development is a fundamental tool for the risk stratification of children and adults, allowing the identification of susceptible or resistant subjects to multiple diseases later in life. Here, we provide a narrative summary of the most relevant evidence supporting the Barker hypothesis in multiple fields of medicine, including neuropsychiatric disorders, such as Parkinson disease and Alzheimer disease, kidney failure, atherosclerosis, coronary heart disease, stroke, diabetes, cancer onset and progression, metabolic syndrome, and infectious diseases including COVID-19. Given the consensus on the role of body weight at birth as a practical indicator of the fetal nutritional status during gestation, every subject with a low birth weight should be considered an “at risk” subject for the development of multiple diseases later in life. The hypothesis of the “physiological regenerative medicine,” able to improve fetal organs’ development in the perinatal period is discussed, in the light of recent experimental data indicating Thymosin Beta-4 as a powerful growth promoter when administered to pregnant mothers before birth.

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Programmed Adult Kidney Disease: Importance of Fetal Environment

Cited by 6 publications

References 101 publications

Effects of Excessive Activation of N-methyl-D-aspartic Acid Receptors in Neonatal Cardiac Mitochondrial Dysfunction Induced by Intrauterine Hypoxia

Effects of Excessive Activation of N-methyl-D-aspartic Acid Receptors in Neonatal Cardiac Mitochondrial Dysfunction Induced by Intrauterine Hypoxia

Parental Programming of Offspring Health: The Intricate Interplay between Diet, Environment, Reproduction and Development

The fascinating theory of fetal programming of adult diseases: A review of the fundamentals of the Barker hypothesis

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