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Brief hyperglycaemia in the early pregnant rat increases fetal weight at term by stimulating placental growth and affecting placental nutrient transport.

Abstract

In pregnant women with type 1 diabetes, suboptimal glucose control in the first trimester is a strong predictor for giving birth to a large fetus. However, the mechanisms underlying this association are unknown. We hypothesized that transient hyperglycaemia in early pregnancy results in (1) increased placental growth and (2) an up-regulation of placental nutrient transport capacity, which leads to fetal overgrowth at term. In order to test this hypothesis, pregnant rats were given intraperitoneal injections of glucose (2 g kg(-1), resulting in a 50-100% increase in blood glucose level during 90 min) or saline (control) in either early or late gestation using four different protocols: one single injection on gestational day (GD) 10 (n=5), three injections on GD 10 (n=8-9), six injections on GD 10 and 11 (n=9-11) or three injections on GD 19 (n=7-8). Multiple injections were given approximately 4 h apart. Subsequently, animals were studied on GD 21. Three glucose injections in early pregnancy significantly increased placental weight by 10%, whereas fetal weight was found to be increased at term in response to both three (9% increase in fetal weight, P<0.05) and six glucose injections (7%, P=0.05) in early gestation. A single glucose injection on GD 10 or three injections of glucose on GD 19 had no effect on placental or fetal growth. In groups where a change in feto-placental growth was observed, we measured placental system A and glucose transport activity in the awake animals on GD 21 and placental expression of the glucose and amino acid transporters GLUT1, GLUT3, SNAT2 (system A), LAT1 and LAT 2 (system L). Placental system A transport at term was down-regulated by six glucose injections in early pregnancy (by -33%, P<0.05), whereas placental mRNA and protein levels were unchanged. No long-term alterations in maternal metabolic status were detected. In conclusion, we demonstrate that transient hyperglycaemia in early pregnancy is sufficient to increase fetal weight close to term. In contrast, brief hyperglycaemia in late pregnancy did not stimulate fetal growth. Increased fetal growth may be explained by a larger placenta, which would allow for more nutrients to be transferred to the fetus. These data suggest that maternal metabolic control in early pregnancy is an important determinant for feto-placental growth and placental function throughout the remainder of gestation. We speculate that maternal metabolism in early pregnancy represents a key environmental cue to which the placenta responds in order to match fetal growth rate with the available resources of the mother.

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  • Authors+Show Affiliations

    ,

    Perinatal Center, Institute of Neuroscience and Physiology, Gothenburg University, Box 432, s-405 30 Gothenburg, Sweden. anette.ericsson@fysiologi.gu.se

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    Source

    The Journal of physiology 581:Pt 3 2007 Jun 15 pg 1323-32

    MeSH

    Amino Acid Transport System y+
    Amino Acid Transport Systems
    Amino Acid Transport Systems, Neutral
    Animals
    Blood Glucose
    Diabetes, Gestational
    Disease Models, Animal
    Female
    Fetal Nutrition Disorders
    Fetal Weight
    Fusion Regulatory Protein 1, Light Chains
    Gestational Age
    Glucose
    Glucose Transport Proteins, Facilitative
    Glucose Transporter Type 1
    Glucose Transporter Type 3
    Hyperglycemia
    Insulin
    Large Neutral Amino Acid-Transporter 1
    Maternal-Fetal Exchange
    Organ Size
    Placenta
    Pregnancy
    RNA, Messenger
    Rats
    Rats, Sprague-Dawley

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    17430988

    Citation

    Ericsson, Anette, et al. "Brief Hyperglycaemia in the Early Pregnant Rat Increases Fetal Weight at Term By Stimulating Placental Growth and Affecting Placental Nutrient Transport." The Journal of Physiology, vol. 581, no. Pt 3, 2007, pp. 1323-32.
    Ericsson A, Säljö K, Sjöstrand E, et al. Brief hyperglycaemia in the early pregnant rat increases fetal weight at term by stimulating placental growth and affecting placental nutrient transport. J Physiol (Lond). 2007;581(Pt 3):1323-32.
    Ericsson, A., Säljö, K., Sjöstrand, E., Jansson, N., Prasad, P. D., Powell, T. L., & Jansson, T. (2007). Brief hyperglycaemia in the early pregnant rat increases fetal weight at term by stimulating placental growth and affecting placental nutrient transport. The Journal of Physiology, 581(Pt 3), pp. 1323-32.
    Ericsson A, et al. Brief Hyperglycaemia in the Early Pregnant Rat Increases Fetal Weight at Term By Stimulating Placental Growth and Affecting Placental Nutrient Transport. J Physiol (Lond). 2007 Jun 15;581(Pt 3):1323-32. PubMed PMID: 17430988.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Brief hyperglycaemia in the early pregnant rat increases fetal weight at term by stimulating placental growth and affecting placental nutrient transport. AU - Ericsson,Anette, AU - Säljö,Karin, AU - Sjöstrand,Eleonor, AU - Jansson,Nina, AU - Prasad,Puttur D, AU - Powell,Theresa L, AU - Jansson,Thomas, Y1 - 2007/04/12/ PY - 2007/4/14/pubmed PY - 2007/8/10/medline PY - 2007/4/14/entrez SP - 1323 EP - 32 JF - The Journal of physiology JO - J. Physiol. (Lond.) VL - 581 IS - Pt 3 N2 - In pregnant women with type 1 diabetes, suboptimal glucose control in the first trimester is a strong predictor for giving birth to a large fetus. However, the mechanisms underlying this association are unknown. We hypothesized that transient hyperglycaemia in early pregnancy results in (1) increased placental growth and (2) an up-regulation of placental nutrient transport capacity, which leads to fetal overgrowth at term. In order to test this hypothesis, pregnant rats were given intraperitoneal injections of glucose (2 g kg(-1), resulting in a 50-100% increase in blood glucose level during 90 min) or saline (control) in either early or late gestation using four different protocols: one single injection on gestational day (GD) 10 (n=5), three injections on GD 10 (n=8-9), six injections on GD 10 and 11 (n=9-11) or three injections on GD 19 (n=7-8). Multiple injections were given approximately 4 h apart. Subsequently, animals were studied on GD 21. Three glucose injections in early pregnancy significantly increased placental weight by 10%, whereas fetal weight was found to be increased at term in response to both three (9% increase in fetal weight, P<0.05) and six glucose injections (7%, P=0.05) in early gestation. A single glucose injection on GD 10 or three injections of glucose on GD 19 had no effect on placental or fetal growth. In groups where a change in feto-placental growth was observed, we measured placental system A and glucose transport activity in the awake animals on GD 21 and placental expression of the glucose and amino acid transporters GLUT1, GLUT3, SNAT2 (system A), LAT1 and LAT 2 (system L). Placental system A transport at term was down-regulated by six glucose injections in early pregnancy (by -33%, P<0.05), whereas placental mRNA and protein levels were unchanged. No long-term alterations in maternal metabolic status were detected. In conclusion, we demonstrate that transient hyperglycaemia in early pregnancy is sufficient to increase fetal weight close to term. In contrast, brief hyperglycaemia in late pregnancy did not stimulate fetal growth. Increased fetal growth may be explained by a larger placenta, which would allow for more nutrients to be transferred to the fetus. These data suggest that maternal metabolic control in early pregnancy is an important determinant for feto-placental growth and placental function throughout the remainder of gestation. We speculate that maternal metabolism in early pregnancy represents a key environmental cue to which the placenta responds in order to match fetal growth rate with the available resources of the mother. SN - 0022-3751 UR - https://www.unboundmedicine.com/medline/citation/17430988/Brief_hyperglycaemia_in_the_early_pregnant_rat_increases_fetal_weight_at_term_by_stimulating_placental_growth_and_affecting_placental_nutrient_transport_ L2 - https://doi.org/10.1113/jphysiol.2007.131185 DB - PRIME DP - Unbound Medicine ER -