Uteroplacental carbon substrate metabolism and O2 consumption after long-term hypoglycemia in pregnant sheep
Abstract
Chronic maternal hypoglycemia leads to fetal growth restriction, but the effects on placental metabolism and its contribution to reduced fetal growth have not been determined. To study these factors, experiments were conducted in seven normal control (C) and six chronically insulin-infused hypoglycemic (H) pregnant sheep over the second half of gestation to measure effects of maternal and fetal hypoglycemia [maternal: 2.0 +/- 0.2 (H) vs. 3.6 +/- 0.1 mM (C); fetal: 0.7 +/- 0.1 (H) vs. 1.1 +/- 0.1 mM (C)] on placental metabolism of glucose, other carbon substrates, and O2. Placental and fetal weight were proportionately reduced in the H group [placental wt: 258 +/- 18 (H) vs. 376 +/- 18 g (C), -31%; fetal wt: 2,540 +/- 190 (H) vs. 3,558 +/- 230 g (C), -29%]. Glucose uptake by the uterus was reduced in the H group [0.10 +/- 0.01 (H) vs. 0.19 +/- 0.02 mmol/min (C)]; it was partitioned more to uteroplacental consumption (UPGC) and less to transfer to the fetus (PGT) [UPGC-to-PGT ratio: 20.0 +/- 2.1 (H) and 13.5 +/- 1.2 (C), P < 0.05 for both]. Metabolism of glucose by nonoxidative and oxidative pathways (as estimated by uteroplacental lactate production-to-UPGC ratio and normal rates of placental O2 consumption) was not significantly changed in the H group. Acetoacetate and beta-hydroxybutyrate net uptake and fructose production rates were significantly reduced in the H group, and there was no change in free fatty acid or amino acid uptake rates. With acute return of maternal and fetal glucose concentrations to normal, UPGC and PGT exceeded normal rates by approximately 25%. Thus chronic reduced glucose supply to the uteroplacenta produces a smaller placenta that uses glucose normally and in preference to transfer to the fetus, demonstrating placental metabolic autonomy at the expense of the fetus.
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With prolonged maternal hypoglycaemia, distribution of uterine glucose uptake between the ovine uteroplacental and fetal tissues shifts to favour the utero-placental tissues, although absolute rates of glucose consumption remain lower than normal.
“With prolonged maternal hypoglycaemia, distribution of uterine glucose uptake between the ovine uteroplacental and fetal tissues shifts to favour the utero-placental tissues, although absolute rates of glucose consumption remain lower than normal (99).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [99]
There is no measureable net uptake of fatty acids by ovine utero-placental tissues in late gestation after prolonged hypoglycaemia.
“Certainly, there is no measureable net uptake of fatty acids by ovine utero-placental tissues in late gestation after prolonged hypoglycaemia (99).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [99]
Even when hyperglycaemia or hypoglycaemia is prolonged in the ewe, placental glucose consumption still varies directly with the maternal glucose concentration.
“Even when hyperglycaemia or hypoglycaemia is prolonged in the ewe, placental glucose consumption still varies directly with the maternal glucose concentration (99, 147).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [99]
Variations in maternal nutritional state have little effect on oxygen consumption by the ovine utero-placental tissues.
“Variations in maternal nutritional state have little effect on oxygen consumption by the ovine utero-placental tissues (99,148,190,554).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [99]
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Placental Origins of Chronic Disease
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- Authors
- Carver, T. D., & Hay, W. W.
- Affiliations
- University of Colorado Anschutz (US)
- ORCID
- Hay, W. W.
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 1995-08-01
- Volume
- 269
- Issue
- 2
- Pages
- E299-E308
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2209248032
- Cited by
- 43
- References
- 18
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2016: 5 · 2015: 2 · 2014: 2 · 2012: 2
- FWCI
- 1.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD028794, HD-28794, HD20761)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
- Keywords
- maternal hypoglycemia, fetal hypoglycemia, placental metabolism, fetal growth restriction, insulin infusion, fructose production, pregnant sheep, placental weight, fetal weight, free fatty acid uptake, amino acid uptake
- MeSH terms
- Animals, Carbon, Chronic Disease, Female, Embryonic and Fetal Development, Fetus, Hypoglycemia, Oxygen Consumption, Placenta, Pregnancy, Pregnancy Complications, Sheep, Substrate Specificity, Uterus
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