scholarly journals Endocrine mechanisms of intrauterine programming

Reproduction ◽  
2004 ◽  
Vol 127 (5) ◽  
pp. 515-526 ◽  
Author(s):  
A L Fowden ◽  
A J Forhead
Keyword(s):  
Growth Factors ◽  
Fetal Growth ◽  
Fetal Development ◽  
Experimental Studies ◽  
In Utero ◽  
Tissue Growth ◽  
Postnatal Life ◽  
Organ Systems ◽  
Intrauterine Programming

Epidemiological findings and experimental studies in animals have shown that individual tissues and whole organ systems can be programmedin uteroduring critical periods of development with adverse consequences for their function in later life. Detailed morphometric analyses of the data have shown that certain patterns of intrauterine growth, particularly growth retardation, can be related to specific postnatal outcomes. Since hormones regulate fetal growth and the development of individual fetal tissues, they have a central role in intrauterine programming. Hormones such as insulin, insulin-like growth factors, thyroxine and the glucocorticoids act as nutritional and maturational signals and adapt fetal development to prevailing intrauterine conditions, thereby maximizing the chances of survival bothin uteroand at birth. However, these adaptations may have long-term sequelae. Of the hormones known to control fetal development, it is the glucocorticoids that are most likely to cause tissue programmingin utero. They are growth inhibitory and affect the development of all the tissues and organ systems most at risk of postnatal pathophysiology when fetal growth is impaired. Their concentrationsin uteroare also elevated by all the nutritional and other challenges known to have programming effects. Glucocorticoids act at cellular and molecular levels to alter cell function by changing the expression of receptors, enzymes, ion channels and transporters. They also alter various growth factors, cytoarchitectural proteins, binding proteins and components of the intracellular signalling pathways. Glucocorticoids act, directly, on genes and, indirectly, through changes in the bioavailability of other hormones. These glucocorticoid-induced endocrine changes may be transient or persist into postnatal life with consequences for tissue growth and development both before and after birth. In the long term, prenatal glucocorticoid exposure can permanently reset endocrine systems, such as the somatotrophic and hypothalamic–pituitary–adrenal axes, which, in turn, may contribute to the pathogenesis of adult disease. Endocrine changes may, therefore, be both the cause and the consequence of intrauterine programming.

scholarly journals Influence of infection during pregnancy on fetal development

Reproduction ◽  
2013 ◽  
Vol 146 (5) ◽  
pp. R151-R162 ◽  
Author(s):  
Kristina M Adams Waldorf ◽  
Ryan M McAdams
Keyword(s):  
Oxidative Stress ◽  
Fetal Growth ◽  
Fetal Development ◽  
Parvovirus B19 ◽  
Treponema Pallidum ◽  
In Utero ◽  
Organ Injury ◽  
Placental Development ◽  
Varicella Zoster

Infection by bacteria, viruses, and parasites may lead to fetal death, organ injury, or limited sequelae depending on the pathogen. Here, we consider the role of infection during pregnancy in fetal development including placental development and function, which can lead to fetal growth restriction. The classical group of teratogenic pathogens is referred to as ‘TORCH’ (Toxoplasma gondii, others likeTreponema pallidum, rubella virus, cytomegalovirus, and herpes simplex virus) but should include a much broader group of pathogens including Parvovirus B19,Varicella zostervirus, andPlasmodium falciparumto name a few. In this review, we describe the influence of different infectionsin uteroon fetal development and the short- and long-term outcomes for the neonate. In some cases, the mechanisms used by these pathogens to disrupt fetal development are well known. Bacterial infection of the developing fetal lungs and brain begins with an inflammatory cascade resulting in cytokine injury and oxidative stress. For some pathogens likeP.falciparum, the mechanisms involve oxidative stress and apoptosis to disrupt placental and fetal growth. Anin uteroinfection may also affect the long-term health of the infant; in many cases, a viral infectionin uteroincreases the risk of developing type 1 diabetes in childhood. Understanding the varied mechanisms employed by these pathogens may enable therapies to attenuate changes in fetal development, decrease preterm birth, and improve survival.

scholarly journals Relative Biological Effectiveness of High LET Particles on the Reproductive System and Fetal Development

Life ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 298
Author(s):  
Bing Wang ◽  
Hiroshi Yasuda
Keyword(s):  
Reproductive System ◽  
Fetal Development ◽  
Relative Biological Effectiveness ◽  
Experimental Studies ◽  
Space Mission ◽  
High Let ◽  
Biological Effectiveness ◽  
Available Information ◽  
Biological Endpoint

During a space mission, astronauts are inevitably exposed to space radiation, mainly composed of the particles having high values of linear energy transfer (LET), such as protons, helium nuclei, and other heavier ions. Those high-LET particles could induce severer health damages than low-LET particles such as photons and electrons. While it is known that the biological effectiveness of a specified type of radiation depends on the distribution of dose in time, type of the cell, and the biological endpoint in respect, there are still large uncertainties regarding the effects of high-LET particles on the reproductive system, gamete, embryo, and fetal development because of the limitation of relevant data from epidemiological and experimental studies. To safely achieve the planned deep space missions to the moon and Mars that would involve young astronauts having reproductive functions, it is crucial to know exactly the relevant radiological effects, such as infertility of the parent and various diseases of the child, and then to conduct proper countermeasures. Thus, in this review, the authors present currently available information regarding the relative biological effectiveness (RBE) of high-LET particles on the deterministic effects related to the reproductive system and embryonic/fetal development for further discussions about the safety of being pregnant after or during a long-term interplanetary mission.

Glucocorticoid-induced changes in glucocorticoid receptor mRNA and protein expression in the human placenta as a potential factor for altering fetal growth and development

2017 ◽  
Vol 29 (5) ◽  
pp. 845 ◽  
Author(s):  
Svetlana Bivol ◽  
Suzzanne J. Owen ◽  
Roselyn B. Rose'Meyer
Keyword(s):  
Fetal Growth ◽  
Growth And Development ◽  
Glucocorticoid Receptors ◽  
Low Birthweight ◽  
Experimental Studies ◽  
Vital Role ◽  
The Body ◽  
Protein Levels ◽  
Organ Systems ◽  
Induced Changes

Glucocorticoids (GCs) control essential metabolic processes in virtually every cell in the body and play a vital role in the development of fetal tissues and organ systems. The biological actions of GCs are mediated via glucocorticoid receptors (GRs), the cytoplasmic transcription factors that regulate the transcription of genes involved in placental and fetal growth and development. Several experimental studies have demonstrated that fetal exposure to high maternal GC levels early in gestation is associated with adverse fetal outcomes, including low birthweight, intrauterine growth restriction and anatomical and structural abnormalities that may increase the risk of cardiovascular, metabolic and neuroendocrine disorders in adulthood. The response of the fetus to GCs is dependent on gender, with female fetuses becoming hypersensitive to changes in GC levels whereas male fetuses develop GC resistance in the environment of high maternal GCs. In this paper we review GR function and the physiological and pathological effects of GCs on fetal development. We propose that GC-induced changes in the placental structure and function, including alterations in the expression of GR mRNA and protein levels, may play role in inhibiting in utero fetal growth.

Endocrine regulation of fetal growth

1995 ◽  
Vol 7 (3) ◽  
pp. 351 ◽  
Author(s):  
AL Fowden
Keyword(s):  
Gene Expression ◽  
Growth Factors ◽  
Fetal Growth ◽  
Growth Regulation ◽  
Fetal Liver ◽  
In Utero ◽  
Tissue Differentiation ◽  
Late Gestation ◽  
Endocrine Regulation ◽  
Tissue Accretion

Hormones have an important role in the control of fetal growth. They act on both tissue accretion and differentiation and enable a precise and orderly pattern of growth to occur during late gestation. In part, their actions on growth may be mediated by other growth factors such as the insulin-like growth factors (IGFs). Insulin stimulates fetal growth by increasing the mitotic drive and nutrient availability for tissue accretion. It has little effect on tissue differentiation. In contrast, the main effects of cortisol in utero are on tissue differentiation and maturation. Cortisol appears to act directly on the cells to alter gene transcription or post-translational processing of the gene products. Cortisol may also initiate the transition from the fetal to the adult modes of growth regulation by inducing the switch from IGF-II to IGF-I gene expression in the fetal liver. Thyroxine affects both tissue accretion and differentiation in the fetus by a combination of metabolic and non-metabolic mechanisms. Pituitary growth hormone, on the other hand, appears to have little part in the control of fetal growth, unlike its role postnatally. Fetal hormones, therefore, promote growth and development in utero by altering both the metabolism and gene expression of the fetal tissues. These hormonal actions ensure that fetal growth rate is commensurate with the nutrient supply and that prepartum maturation occurs in preparation for extrauterine life.

scholarly journals 234 In utero heat stress alters the postnatal immune and metabolic response of growing pigs subjected to a lipopolysaccharide challenge

2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 116-116
Author(s):  
Jay S Johnson ◽  
Jacob M Maskal ◽  
Alan W Duttlinger ◽  
Kouassi R Kpodo ◽  
Betty R McConn ◽  
...  
Keyword(s):  
Heat Stress ◽  
Body Temperature ◽  
Metabolic Response ◽  
In Utero ◽  
Growing Pigs ◽  
Postnatal Life ◽  
Study Objective ◽  
Lps Challenge ◽  
Long Term Impact

Abstract In utero heat stress (IUHS) reduces swine productivity and welfare but little is known about the long-term impact on immune function. The study objective was to determine the effects of IUHS on the immune and metabolic response of pigs subjected to an 8 h lipopolysaccharide (LPS) challenge during postnatal life. Twenty-four pregnant gilts were exposed to thermoneutral (TN; n = 12; 17.5 ± 2.1⁰C) or heat stress (HS; n = 12; cyclical 27°C-37°C) conditions from d 1 to 58 of gestation, and TN conditions from d 59 of gestation to farrowing. After farrowing, all piglets were housed under the same conditions. At 12 weeks post-farrowing, 16 IUHS and 16 in utero thermoneutral (IUTN) pigs were selected, balanced by sex and given an intravenous injection of LPS (2 µg/kg BW) or saline (SAL). Treatment combinations were: IUTN-SAL, IUTN-LPS, IUHS-SAL, IUHS-LPS. Body temperature was monitored in 30-min intervals and blood samples were obtained at 0, 1, 2, 3, 4, 6, and 8 h. Blood was analyzed for glucose, insulin, non-esterified fatty acids (NEFA), and cytokine concentrations. Body temperature increased (P < 0.01; 1.05°C) in LPS versus SAL pigs, regardless of in utero treatment. Glucose concentrations were reduced overall (P = 0.05; 5.9%) in IUHS versus IUTN pigs. Non-esterified fatty acid concentrations tended to be greater (P = 0.07; 143.4%) in IUHS-LPS pigs compared to all other treatments, and IUTN-LPS pigs tended to have greater circulating NEFA concentrations (127.4%) compared to IUTN-SAL and IUHS-SAL pigs. At 1 h, TNFα was increased (P = 0.01; 115.1%) in IUHS-LPS compared to IUTN-LPS pigs. Overall, IL-1β and IL-6 were greater (P < 0.04; 56.0 and 46.8%, respectively) in IUHS-LPS compared IUTN-LPS pigs. In summary, IUHS altered the postnatal immune and metabolic response of pigs during postnatal life, which has negative implications towards future disease susceptibility.

scholarly journals The application of in utero magnetic resonance imaging in the study of the metabolic and cardiovascular consequences of the developmental origins of health and disease

2020 ◽  
pp. 1-10
Author(s):  
Stephanie A. Giza ◽  
Simran Sethi ◽  
Lauren M. Smith ◽  
Mary-Ellen E. T. Empey ◽  
Lindsay E. Morris ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Adipose Tissue ◽  
Magnetic Resonance ◽  
Fetal Growth ◽  
Fetal Development ◽  
In Utero ◽  
Developmental Origins ◽  
Organ Development ◽  
Resonance Imaging ◽  
Health And Disease

Abstract Observing fetal development in utero is vital to further the understanding of later-life diseases. Magnetic resonance imaging (MRI) offers a tool for obtaining a wealth of information about fetal growth, development, and programming not previously available using other methods. This review provides an overview of MRI techniques used to investigate the metabolic and cardiovascular consequences of the developmental origins of health and disease (DOHaD) hypothesis. These methods add to the understanding of the developing fetus by examining fetal growth and organ development, adipose tissue and body composition, fetal oximetry, placental microstructure, diffusion, perfusion, flow, and metabolism. MRI assessment of fetal growth, organ development, metabolism, and the amount of fetal adipose tissue could give early indicators of abnormal fetal development. Noninvasive fetal oximetry can accurately measure placental and fetal oxygenation, which improves current knowledge on placental function. Additionally, measuring deficiencies in the placenta’s transport of nutrients and oxygen is critical for optimizing treatment. Overall, the detailed structural and functional information provided by MRI is valuable in guiding future investigations of DOHaD.

scholarly journals Thyroid hormones in fetal growth and prepartum maturation

2014 ◽  
Vol 221 (3) ◽  
pp. R87-R103 ◽  
Author(s):  
A J Forhead ◽  
A L Fowden
Keyword(s):  
Growth Factors ◽  
Thyroid Hormones ◽  
Fetal Growth ◽  
Growth And Development ◽  
Fetal Brain ◽  
Normal Growth ◽  
In Utero ◽  
Somatic Tissues ◽  
Near Term ◽  
Maternal Thyroid

The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are essential for normal growth and development of the fetus. Their bioavailabilityin uterodepends on development of the fetal hypothalamic–pituitary–thyroid gland axis and the abundance of thyroid hormone transporters and deiodinases that influence tissue levels of bioactive hormone. Fetal T4and T3concentrations are also affected by gestational age, nutritional and endocrine conditionsin utero, and placental permeability to maternal thyroid hormones, which varies among species with placental morphology. Thyroid hormones are required for the general accretion of fetal mass and to trigger discrete developmental events in the fetal brain and somatic tissues from early in gestation. They also promote terminal differentiation of fetal tissues closer to term and are important in mediating theprepartummaturational effects of the glucocorticoids that ensure neonatal viability. Thyroid hormones act directly through anabolic effects on fetal metabolism and the stimulation of fetal oxygen consumption. They also act indirectly by controlling the bioavailability and effectiveness of other hormones and growth factors that influence fetal development such as the catecholamines and insulin-like growth factors (IGFs). By regulating tissue accretion and differentiation near term, fetal thyroid hormones ensure activation of physiological processes essential for survival at birth such as pulmonary gas exchange, thermogenesis, hepatic glucogenesis, and cardiac adaptations. This review examines the developmental control of fetal T4and T3bioavailability and discusses the role of these hormones in fetal growth and development with particular emphasis on maturation of somatic tissues critical for survival immediately at birth.

scholarly journals Fetal growth restriction: adaptations and consequences

Reproduction ◽  
2001 ◽  
pp. 195-204 ◽  
Author(s):  
IC McMillen ◽  
MB Adams ◽  
JT Ross ◽  
CL Coulter ◽  
G Simonetta ◽  
...  
Keyword(s):  
Health Outcomes ◽  
Fetal Growth ◽  
Experimental Studies ◽  
Adult Health ◽  
Critical Importance ◽  
Intrauterine Environment ◽  
Placental Function ◽  
Metabolic Adaptations ◽  
Physiological Adaptations

A range of pathophysiological factors can result in a perturbation or restriction of fetal growth, and the cardiovascular, neuroendocrine and metabolic adaptations of the fetus to these stimuli will depend on their nature, timing and intensity. The critical importance of these physiological adaptations for both immediate survival and long-term health outcomes has provided an impetus for experimental studies of the nature and consequences of specific fetal adaptations to a poor intrauterine environment. This review summarizes data from recent studies that have focused on the responses of the fetal cardiovascular, sympathoadrenal, hypothalamo-pituitary-adrenal and renin-angiotensin systems to experimental restriction of placental function in the sheep and discusses the consequences of these adaptations for fetal, neonatal and adult health.

scholarly journals In-utero stress and mode of conception: impact on regulation of imprinted genes, fetal development and future health

2019 ◽  
Vol 25 (6) ◽  
pp. 777-801 ◽  
Author(s):  
Maria Argyraki ◽  
Pauliina Damdimopoulou ◽  
Katerina Chatzimeletiou ◽  
Grigoris F Grimbizis ◽  
Basil C Tarlatzis ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Psychological Stress ◽  
Genomic Imprinting ◽  
Fetal Growth ◽  
Fetal Development ◽  
Environmental Chemicals ◽  
Imprinted Genes ◽  
Epigenetic Patterns

AbstractBACKGROUNDGenomic imprinting is an epigenetic gene regulatory mechanism; disruption of this process during early embryonic development can have major consequences on both fetal and placental development. The periconceptional period and intrauterine life are crucial for determining long-term susceptibility to diseases. Treatments and procedures in assisted reproductive technologies (ART) and adverse in-utero environments may modify the methylation levels of genomic imprinting regions, including insulin-like growth factor 2 (IGF2)/H19, mesoderm-specific transcript (MEST), and paternally expressed gene 10 (PEG10), affecting the development of the fetus. ART, maternal psychological stress, and gestational exposures to chemicals are common stressors suspected to alter global epigenetic patterns including imprinted genes.OBJECTIVE AND RATIONALEOur objective is to highlight the effect of conception mode and maternal psychological stress on fetal development. Specifically, we monitor fetal programming, regulation of imprinted genes, fetal growth, and long-term disease risk, using the imprinted genes IGF2/H19, MEST, and PEG10 as examples. The possible role of environmental chemicals in genomic imprinting is also discussed.SEARCH METHODSA PubMed search of articles published mostly from 2005 to 2019 was conducted using search terms IGF2/H19, MEST, PEG10, imprinted genes, DNA methylation, gene expression, and imprinting disorders (IDs). Studies focusing on maternal prenatal stress, psychological well-being, environmental chemicals, ART, and placental/fetal development were evaluated and included in this review.OUTCOMESIGF2/H19, MEST, and PEG10 imprinted genes have a broad developmental effect on fetal growth and birth weight variation. Their disruption is linked to pregnancy complications, metabolic disorders, cognitive impairment, and cancer. Adverse early environment has a major impact on the developing fetus, affecting mostly growth, the structure, and subsequent function of the hypothalamic–pituitary–adrenal axis and neurodevelopment. Extensive evidence suggests that the gestational environment has an impact on epigenetic patterns including imprinting, which can lead to adverse long-term outcomes in the offspring. Environmental stressors such as maternal prenatal psychological stress have been found to associate with altered DNA methylation patterns in placenta and to affect fetal development. Studies conducted during the past decades have suggested that ART pregnancies are at a higher risk for a number of complications such as birth defects and IDs. ART procedures involve multiple steps that are conducted during critical windows for imprinting establishment and maintenance, necessitating long-term evaluation of children conceived through ART. Exposure to environmental chemicals can affect placental imprinting and fetal growth both in humans and in experimental animals. Therefore, their role in imprinting should be better elucidated, considering the ubiquitous exposure to these chemicals.WIDER IMPLICATIONSDysregulation of imprinted genes is a plausible mechanism linking stressors such as maternal psychological stress, conception using ART, and chemical exposures with fetal growth. It is expected that a greater understanding of the role of imprinted genes and their regulation in fetal development will provide insights for clinical prevention and management of growth and IDs. In a broader context, evidence connecting impaired imprinted gene function to common diseases such as cancer is increasing. This implies early regulation of imprinting may enable control of long-term human health, reducing the burden of disease in the population in years to come.

Nutrition and fetal growth

1995 ◽  
Vol 7 (3) ◽  
pp. 539 ◽  
Author(s):  
JE Harding ◽  
BM Johnston
Keyword(s):  
Fetal Growth ◽  
Minor Component ◽  
Building Blocks ◽  
Tissue Growth ◽  
Maternal Undernutrition ◽  
Substrate Supply ◽  
Key Factor ◽  
A Minor ◽  
Substrate Deprivation

Nutrient supply to the fetus is a key factor in the regulation of fetal growth. However, the direct supply of nutrients to provide building blocks for tissue growth is likely to be only a minor component of this regulation. The indirect effects of nutrition on fetal endocrine and metabolic status, and on the interaction between the fetus, placenta and mother all of which must be coordinated to allow fetal growth are also important. Maternal undernutrition may alter the growth of the fetus and its different component tissues in a way which cannot be explained solely on the basis of reduced substrate supply during the rapid growth phase of the tissues involved. Adaptation to altered substrate supply, during both undernutrition and refeeding, involves sequential changes in the metabolic and endocrine interactions between the fetus and the placenta. In addition, undernutrition has long-term consequences for the fetus. There is evidence for nutritional programming of fetal endocrine and cardiovascular systems before birth. Nutritional effects may also persist over more than one generation. The effects of nutrition on fetal growth are far more complex than simply those of substrate deprivation.

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