Restriction of placental function alters heart development in the sheep fetus

2007 ◽  
Vol 293 (1) ◽  
pp. R306-R313 ◽  
Author(s):  
J. L. Morrison ◽  
K. J. Botting ◽  
J. L. Dyer ◽  
S. J. Williams ◽  
K. L. Thornburg ◽  
...  

Placental insufficiency, resulting in restriction of fetal substrate supply, is a major cause of intrauterine growth restriction (IUGR) and increased neonatal morbidity. Fetal adaptations to placental restriction maintain the growth of key organs, including the heart, but the impact of these adaptations on individual cardiomyocytes is unknown. Placental and hence fetal growth restriction was induced in fetal sheep by removing the majority of caruncles in the ewe before mating (placental restriction, PR). Vascular surgery was performed on 13 control and 11 PR fetuses at 110–125 days of gestation (term: 150 ± 3 days). PR fetuses with a mean gestational Po2 < 17 mmHg were defined as hypoxic. At postmortem (<135 or >135 days), fetal hearts were collected, and cardiomyocytes were isolated and fixed. Proliferating cardiomyocytes were counted by immunohistochemistry of Ki67 protein. Cardiomyocytes were stained with methylene blue to visualize the nuclei, and the proportion of mononucleated cells and length and width of cardiomyocytes were measured. PR resulted in chronic fetal hypoxia, IUGR, and elevated plasma cortisol concentrations. Although there was no difference in relative heart weights between control and PR fetuses, there was an increase in the proportion of mononucleated cardiomyocytes in PR fetuses. Whereas mononucleated and binucleated cardiomyocytes were smaller, the relative size of cardiomyocytes when expressed relative to heart weight was larger in PR compared with control fetuses. The increase in the relative proportion of mononucleated cardiomyocytes and the relative sparing of the growth of individual cardiomyocytes in the growth-restricted fetus are adaptations that may have long-term consequences for heart development in postnatal life.

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3399
Author(s):  
Yasaman Shahkhalili ◽  
Florence Blancher-Budin ◽  
Cathriona Monnard ◽  
Julie Moulin ◽  
José Sanchez-Garcia ◽  
...  

The impact of early life protein source (whey vs. casein) on short- and long-term glucose homeostasis and adiposity is unknown and was investigated in this study. At the end of the suckling period, non-IUGR (intrauterine growth restriction) and IUGR pups were separated from dams and were randomized into four groups. From age 21–49 days, non-IUGR and IUGR pups were fed ad-libitum chow or a semi-synthetic diet (20% from protein; casein or whey) and from age 50–199 days, all groups were fed ad-libitum chow. Food intake, body composition, glucose, and insulin homeostasis were assessed. Among the chow groups, IUGR had slower growth and higher fasting glucose at age 42 days, as well as higher fasting and AUC glucose at age 192 days relative to non-IUGR. The whey IUGR group had a slower growth rate and higher fasting glycemia in early life (age 21–49 days) and higher HOMA-IR later in life (age 120–122 and 190–192 days) relative to casein IUGR. This study shows the potential advantage of casein relative to whey during weaning on short term energy intake, growth, and glucose homeostasis in an IUGR model and reveals, for the first time, its long term impact on insulin sensitivity, which may have implications for later metabolic health, particularly in small-for-gestational-age populations at risk of type 2 diabetes.


2016 ◽  
Vol 4 (3) ◽  
pp. 675-684 ◽  
Author(s):  
Maarten Lupker ◽  
Christian France-Lanord ◽  
Bruno Lartiges

Abstract. Continental-scale chemical weathering budgets are commonly assessed based on the flux of dissolved elements carried by large rivers to the oceans. However, the interaction between sediments and seawater in estuaries can lead to additional cation exchange fluxes that have been very poorly constrained so far. We constrained the magnitude of cation exchange fluxes from the Ganga–Brahmaputra river system based on cation exchange capacity (CEC) measurements of riverine sediments. CEC values of sediments are variable throughout the river water column as a result of hydrological sorting of minerals with depth that control grain sizes and surface area. The average CEC of the integrated sediment load of the Ganga–Brahmaputra is estimated ca. 6.5 meq 100 g−1. The cationic charge of sediments in the river is dominated by bivalent ions Ca2+ (76 %) and Mg2+ (16 %) followed by monovalent K+ (6 %) and Na+ (2 %), and the relative proportion of these ions is constant among all samples and both rivers. Assuming a total exchange of exchangeable Ca2+ for marine Na+ yields a maximal additional Ca2+ flux of 28  ×  109 mol yr−1 of calcium to the ocean, which represents an increase of ca. 6 % of the actual river dissolved Ca2+ flux. In the more likely event that only a fraction of the adsorbed riverine Ca2+ is exchanged, not only for marine Na+ but also Mg2+ and K+, estuarine cation exchange for the Ganga–Brahmaputra is responsible for an additional Ca2+ flux of 23  ×  109 mol yr−1, while ca. 27  ×  109 mol yr−1 of Na+, 8  ×  109 mol yr−1 of Mg2+ and 4  ×  109 mol yr−1 of K+ are re-absorbed in the estuaries. This represents an additional riverine Ca2+ flux to the ocean of 5 % compared to the measured dissolved flux. About 15 % of the dissolved Na+ flux, 8 % of the dissolved K+ flux and 4 % of the Mg2+ are reabsorbed by the sediments in the estuaries. The impact of estuarine sediment–seawater cation exchange appears to be limited when evaluated in the context of the long-term carbon cycle and its main effect is the sequestration of a significant fraction of the riverine Na flux to the oceans. The limited exchange fluxes of the Ganga–Brahmaputra relate to the lower than average CEC of its sediment load that do not counterbalance the high sediment flux to the oceans. This can be attributed to the nature of Himalayan river sediment such as low proportion of clays and organic matter.


2019 ◽  
Vol 97 (6) ◽  
pp. 457-462 ◽  
Author(s):  
Paramjit S. Tappia ◽  
Bram Ramjiawan

Poor quality and quantity maternal nutrition during pregnancy exerts permanent and damaging effects on the heart of the developing fetus. The developmental origin of adult heart disease is considered an important and critical factor in the pathogenesis of myocardial abnormalities in later life. Low birth mass, a marker of intrauterine stress, has been linked to a predisposition to heart disease. In this article, our work on the impact of exposure to a low-protein diet, in utero, on the developing heart and its long-term consequences are discussed. Other studies providing some supportive evidence are also described. It is proposed that normal fetal nutrition, growth, and development through efficient maternal nutrition (as well as other predisposing factors) before and during pregnancy may serve as a strategy for the primary prevention of heart disease.


Author(s):  
Alexandra Paul ◽  
Rebecca Deans ◽  
Russell Viner ◽  
Sarah M. Creighton

Abstract Introduction: Premature infants, especially very low birth weight infants, and fetal growth restriction are a challenge for healthcare professionals alike owing to the consequences of these conditions. Objective: To provide information for gynecologists, pediatricians and neonatologists to identify correct outcome expectations to help them plan their preventive and therapeutic actions. Searches were made on the MEDLINE database. Results: According to several follow-up studies, there is an increasing evidence for a link between early life exposures (prenatal and postnatal) and long-term outcomes. An adverse in utero environment will induce fetal reprogramming of neuroendocrine axes with permanent alterations of the physiology and metabolism of various body structures and functioning of neuroendocrine axes in later life, leading to a variety of different conditions, such as persistence of neurodevelopmental disability, changes in growth pattern, in body metabolism, in pubertal development, lower educational achievement and even psychological disturbances with possible alterations of sexual behavior in female adolescents and young adults. In addition, short-term transitory consequences can be also present, such as anomalies in genital appearance. Conclusions: Outcome studies on the impact that prematurity, low birth weight and intrauterine growth restriction have on pubertal development, sexuality and fertility are still scarce. Long-term outcomes of small for gestational age or preterm adolescents are complex and multifactorial, with interactions between genetic and environmental influences involving different pathways of adaptive responses during crucial phases of prenatal growth.


2017 ◽  
Vol 30 (9) ◽  
pp. 589
Author(s):  
Gabriela Mimoso ◽  
Guiomar Oliveira

Introduction: Gestational diabetes is one of the diseases associated with pregnancy with higher rate of complications. Despite being a transitory condition, short and long term complications related to gestational diabetes have been described. There is scientific evidence to say that good metabolic control decreases perinatal complications. In 2011, new criteria was proposed for its diagnosis, which made possible its diagnosis during the 1st trimester of pregnancy. The aim of this study is to compare neonatal morbidity in two groups of women with gestational diabetes diagnosis before and after the latest Portuguese guidelines for diabetes and pregnancy were published (February 2011).Material and Methods: We included all newborns born in Maternidade Bissaya Barreto whose mother, followed at our maternity between 2008 and 2013, had unifetal pregnancy complicated by diabetes. We used a perinatal database and analysed the impact of the new guidelines in perinatal morbidity over two periods of three years.Results: There were 774 women who met the inclusion criteria. We found that gestational diabetes was diagnosed earlier, insulin therapy was more frequent. Neonatal morbidity was increased, and there were more cases of neonatal hypoglycemia and congenital anomalies, and newborns became smaller for gestational age.Discussion: The increase in neonatal morbidity was associated with early diagnosis and rigorous metabolic control.Conclusion: To analyse national data will be fundamental to understand this unexpected increase in morbidity.


1997 ◽  
Vol 272 (1) ◽  
pp. R201-R207 ◽  
Author(s):  
J. Murotsuki ◽  
J. R. Challis ◽  
V. K. Han ◽  
L. J. Fraher ◽  
R. Gagnon

To examine the cardiovascular effects on the fetus of an elevated umbilical vascular resistance resulting in fetal hypoxemia, we embolized the fetal side of the placenta in pregnant sheep and measured cardiovascular and hormonal changes and cellular growth in fetal heart. Chronically catheterized fetal sheep were embolized (n = 6) for 21 days between 0.74 and 0.88 of gestation into the descending aorta until arterial oxygen content was decreased by 40-50% of the preembolization value. Control animals (n = 6) received saline only. During embolization, fetuses became chronically hypoxemic (P < 0.001) and hypertensive (P < 0.001), with a progressive increase in umbilical artery resistance index (P < 0.001). There was also an increase in fetal plasma norepinephrine throughout the study period (P < 0.05). On day 21 of embolization, fetuses showed asymmetrical growth restriction, increased heart weight (P < 0.01), and increase in right and left ventricular wall thickness (P < 0.05) compared with control animals. The protein-to-DNA ratio, an index of cell size, increased in the right ventricular myocardium in the embolized group (P < 0.001), suggesting myocardial cell hypertrophy. We conclude that, during chronic placental damage leading to fetal hypoxemia with an increase in umbilical artery resistance index, fetuses developed arterial hypertension and asymmetrical growth restriction and that increases in afterload to the heart and plasma norepinephrine likely caused fetal myocardial hypertrophy.


2013 ◽  
Vol 45 (3) ◽  
pp. 99-105 ◽  
Author(s):  
Glenn D. Wadley ◽  
Glenn K. McConell ◽  
Craig A. Goodman ◽  
Andrew L. Siebel ◽  
Kerryn T. Westcott ◽  
...  

This study investigated the impact of uteroplacental insufficiency and growth restriction on the expression of genes related to mitochondrial biogenesis, glucose transport, and antioxidant defenses in cardiac tissue at embryonic day 20 (E20) and postnatal days 1, 7, and 35 in male and female Wistar rats (8–10 per group). Bilateral uterine vessel ligation to induce growth restriction (Restricted) or sham surgery was performed at pregnancy day 18. In male and female Controls, expression of most cardiac genes decreased during postnatal life, including genes involved in mitochondrial biogenesis regulation such as PGC-1α, NRF-2, and mtTFA and the glucose transporter GLUT-1 ( P < 0.05). However, the pattern of gene expression during cardiac development differed in male and female Restricted rats compared with their respective Controls. These effects of restriction were observed at postnatal day 1, with female Restricted rats having delayed reductions in PGC-1α and GLUT-1, whereas males had exacerbated reductions in PGC-1α and mtTFA ( P < 0.05). By day 35, cardiac gene expression in Restricted hearts was similar to Controls, except for expression of the antioxidant enzyme MnSOD, which was significantly lower in both sexes. In summary, during postnatal life male and female Control rats have similar patterns of expression for genes involved in mitochondrial biogenesis and glucose transport. However, following uteroplacental insufficiency these gene expression patterns diverge in males and females during early postnatal life, with MnSOD gene expression reduced in later postnatal life.


2016 ◽  
Author(s):  
Maarten Lupker ◽  
Christian France-Lanord ◽  
Bruno Lartiges

Abstract. Continental scale chemical weathering budgets are commonly assessed based on the flux of dissolved elements carried by large rivers to the oceans. However the interaction between sediments and seawater in estuaries can lead to additional cation exchange fluxes that have been very poorly constrained so far. We constrained the magnitude of cation exchange fluxes from the Ganges-Brahmaputra River system based on cation exchange capacity (CEC) measurements of riverine sediments. CEC values of sediments are variable throughout the water column but average at ca. 6.5 meq/100 g for the Ganges-Brahmaputra. The cationic charge of sediments in the river is dominated by bivalent ions Ca2+ (76 %) and Mg2+ (16 %) followed by monovalent K+ (6 %) and Na+ (2 %) and the relative proportion of these ions is constant among all samples and rivers. Assuming a total exchange of exchangeable Ca2+ for marine Na+ yields an maximal additional Ca2+ flux of 28 x 109 mol/yr of calcium to the ocean, which represents an increase of ca. 6 % of the actual dissolved Ca2+ flux. In the more likely event that only a fraction of the adsorbed riverine Ca2+ is exchanged, not only for marine Na+ but also Mg2+ and K+, estuarine cation exchange for the Ganga-Brahmaputra is responsible for an additional Ca2+ flux of 23 x 109 mol/yr, while ca. 27 x 109 mol/yr of Na+, 8 x 109 mol/yr of Mg2+ and 4 x 109 mol/yr of K+ are re-absorbed in the estuaries. This represents an additional riverine Ca2+ flux to the ocean of 5 % compared to the measured dissolved flux. About 15 % of the dissolved Na+ flux, 8 % of the dissolved K+ flux and 4 % of the Mg2+ are reabsorbed by the sediments in the estuaries. The impact of estuarine sediment-seawater cation exchange is therefore limited if evaluated in the context of the long-term carbon cycle and its main effect is the sequestration of a significant fraction of the riverine Na flux to the oceans.


Endocrinology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 26-33 ◽  
Author(s):  
Gurjeev Sohi ◽  
Andrew Revesz ◽  
Julie Ramkumar ◽  
Daniel B. Hardy

Abstract A nutritional mismatch in postnatal life of low birth weight offspring increases the risk of developing the metabolic syndrome. Moreover, this is associated with decreased hepaticIgf1 expression, leading to impaired growth and metabolism. Previously, we have demonstrated that the timing of nutritional restoration in perinatal life can differentially program hepatic gene expression. Although microRNAs also play an important role in silencing gene expression, to date, the impact of a nutritional mismatch in neonatal life on their long-term expression has not been evaluated. Given the complementarity of miR-29 to the 3′ untranslated region of Igf1, we examined how protein restoration in maternal protein restriction rat offspring influences hepatic miR-29 and Igf1 expression in adulthood. Pregnant Wistar rats were designated into 1 of 4 dietary regimes: 20% protein (control), 8% protein during lactation only (LP-Lact), 8% protein during gestation only (LP1) or both (LP2). The steady-state expression of hepatic miR-29 mRNAsignificantly increased in LP2 offspring at postnatal day 21 and 130, and this was inversely related to hepatic Igf1 mRNA and body weight. Interestingly, this reciprocal association was stronger in LP-Lact offspring at postnatal day 21. Functional relevance of this in vivo relationship was evaluated by transfection of miR-29 mimics in neonatal Clone 9 rat hepatoma cells. Transfection with miR-29 suppressed Igf1 expression by 12 hours. Collectively, these findings implicate that nutritional restoration after weaning (post liver differentiation) in maternal protein restriction rat offspring fails to prevent long-term impaired growth, in part, due to miR-29 suppression of hepatic Igf1 expression. (Endocrinology 156: 3069–3076, 2015)


2020 ◽  
Vol 32 (2) ◽  
pp. 82 ◽  
Author(s):  
Luiz G. Siqueira ◽  
Marcos V. G. Silva ◽  
João C. Panetto ◽  
João H. Viana

Abnormal fetuses, neonates and adult offspring derived by assisted reproductive technologies (ART) have been reported in humans, rodents and domestic animals. The use of ART has also been associated with an increased likelihood of certain adult diseases. These abnormalities may arise as a result of an excess of or missing maternally derived molecules during invitro culture, because the invitro environment is artificial and suboptimal for embryo development. Nonetheless, the success of ART in overcoming infertility or improving livestock genetics is undeniable. Limitations of invitro embryo production (IVEP) in cattle include lower rates of the establishment and maintenance of pregnancy and an increased incidence of neonatal morbidity and mortality. Moreover, recent studies demonstrated long-term effects of IVEP in cattle, including increased postnatal mortality, altered growth and a slight reduction in the performance of adult dairy cows. This review addresses the effects of an altered preimplantation environment on embryo and fetal programming and offspring development. We discuss cellular and molecular responses of the embryo to the maternal environment, how ART may disturb programming, the possible role of epigenetic effects as a mechanism for altered phenotypes and long-term effects of ART that manifest in postnatal life.


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