ArticleBiology of reproduction2019
Maternal L-proline supplementation enhances fetal survival, placental development, and nutrient transport in mice†.
Article in Biology of reproduction, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- Targeted Intracellular Delivery of Amino Acids to Trophoblast Cells Reveals Proteomic Signatures of Cellular Utilisation.Biomolecules · 2026Article
- The Metabolic-Immune Axis: Amino Acids and Immune Cell Dynamics in Mammary Gland Development and Remodeling.International journal of biological sciences · 2026Review
- Dietary Proline Supplementation Promotes Growth and Development in Weaned Foals by Modulating Gut Microbial Amino Acid Metabolism.Microorganisms · 2025Article
- Amino Acid Restriction Impairs Human Endometrial Stromal Cell Decidualization and Is Rescued by Proline Supplementation.Journal of cellular and molecular medicine · 2025Article
- Increased proline intake during gestation alleviates obesity-related impaired fetal development and placental function in gilts.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- Increasing the Understanding of Nutrient Transport Capacity of the Ovine Placentome.Animals : an open access journal from MDPI · 2024Article
- Amino acid profiles: exploring their diagnostic and pathophysiological significance in hypertension.Molecular biology reports · 2024Review
- Non-Targeted Metabolomic Study of Fetal Growth Restriction.Metabolites · 2023Article
- Metabonomic analysis of follicular fluid in patients with diminished ovarian reserve.Frontiers in endocrinology · 2023Article
- Omics profiling identifies the regulatory functions of the MAPK/ERK pathway in nephron progenitor metabolism.Development (Cambridge, England) · 2022Article
- Review
- A review of the amino acid metabolism in placental function response to fetal loss and low birth weight in pigs.Journal of animal science and biotechnology · 2022Review
- Placental Angiogenesis in Mammals: A Review of the Regulatory Effects of Signaling Pathways and Functional Nutrients.Advances in nutrition (Bethesda, Md.) · 2021Review
- SupplementingAnimal nutrition (Zhongguo xu mu shou yi xue hui) · 2021Article
- Impact of Dietary Crude Protein Level on Hepatic Lipid Metabolism in Weaned Female Piglets.Animals : an open access journal from MDPI · 2021Article
- L-Proline Activates Mammalian Target of Rapamycin Complex 1 and Modulates Redox Environment in Porcine Trophectoderm Cells.Biomolecules · 2021Article
- Supplementation with Proline Improves Haemato-Biochemical and Reproductive Indicators in Male Rabbits Affected by Environmental Heat-Stress.Animals : an open access journal from MDPI · 2021Article
- Placental Impact of Dietary Supplements: More Than Micronutrients.Clinical therapeutics · 2021Review
- Amino Acids in Swine Nutrition and Production.Advances in experimental medicine and biology · 2021Article
- The Multifaceted Roles of Proline in Cell Behavior.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
L-Proline (proline) in amniotic fluid was markedly increased during pregnancy in both pigs and sheep. However, in vivo data to support a beneficial effect of proline on fetal survival are not available. In this study, pregnant C57BL/6J mice were fed a purified diet supplemented with or without 0.50% proline from embryonic day 0.5 (E0.5) to E12.5 or term. Results indicated that dietary supplementation with proline to gestating mice enhanced fetal survival, reproductive performance, the concentrations of proline, arginine, aspartic acid, and tryptophan in plasma and amniotic fluid, while decreasing the concentrations of ammonia and urea in plasma and amniotic fluid. Placental mRNA levels for amino acid transporters, including Slc36a4, Slc38a2, Slc38a4, Slc6a14, and Na+/K+ ATPase subunit-1α (Atp1a1), fatty acid transporter Slc27a4, and glucose transporters Slc2a1 and Slc2a3, were augmented in proline-supplemented mice, compared with the control group. Histological analysis showed that proline supplementation enhanced labyrinth zone in the placenta of mice at E12.5, mRNA levels for Vegf, Vegfr, Nos2, and Nos3, compared with the controls. Western blot analysis showed that proline supplementation increased protein abundances of phosphorylated (p)-mTORC1, p-ribosomal protein S6 kinase (p70S6K), and p-eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), as well as the protein level of GCN2 (a negative regulator of mTORC1 signaling). Collectively, our results indicate a novel functional role of proline in improving placental development and fetal survival by enhancing placental nutrient transport, angiogenesis, and protein synthesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.