ArticlePLoS computational biology2021
One-carbon metabolism during the menstrual cycle and pregnancy.
Article in PLoS computational biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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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
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- An integrated multi-tissue approach for endometriosis candidate biomarkers: a systematic review.Reproductive biology and endocrinology : RB&E · 2024Pooled it
- Modeling ovarian hormone effects on glucose-insulin control in type 1 diabetes.Bioengineering & translational medicine · 2026Review
- Ischemic Stroke Increases Protein Expression of the Folate Receptor and One-carbon Enzymes in Brain Tissue From Male and Female Patients.Translational stroke research · 2026Article
- One-carbon metabolism and cardiovascular disease: Molecular mechanisms, genetic influences, and epigenetic regulation.Biochemistry and biophysics reports · 2026Review
- Sex and gender differences in responses to antianemic therapies: biological mechanisms and clinical implications.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- The Role of Estradiol in Oxidative Stress in Health and Cystathionine ß-Synthase Deficiency: A Mechanistic Model.CPT: pharmacometrics & systems pharmacology · 2026Article
- Maternal red blood cell folate metabolites were dynamically associated with neonatal amino acids and acylcarnitines in heel blood: a prospective cohort study.Nutrition & metabolism · 2026Article
- Elevated Homocysteine is Associated With Liver Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease in a Sex- and Menopause-Specific Manner.Gastro hep advances · 2026Article
- Differential effects of synthetic estrogen on serum homocysteine levels before and after menopause.PloS one · 2025Article
- Steroids and One-Carbon Metabolism: Clinical Implications in Endocrine Disorders.Neuroendocrinology · 2025Review
- Independent effects of testosterone, estradiol, and sex chromosomes on gene expression in immune cells of trans- and cisgender individuals.bioRxiv : the preprint server for biology · 2024Article
- Longitudinal Analysis of One-Carbon Metabolism-Related Metabolites in Maternal and Cord Blood of Japanese Pregnant Women.Nutrients · 2024Article
- The Role of One-Carbon Metabolism and Methyl Donors in Medically Assisted Reproduction: A Narrative Review of the Literature.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Many enzymes in one-carbon metabolism (OCM) are up- or down-regulated by the sex hormones which vary diurnally and throughout the menstrual cycle. During pregnancy, estradiol and progesterone levels increase tremendously to modulate physiological changes in the reproductive system. In this work, we extend and improve an existing mathematical model of hepatic OCM to understand the dynamic metabolic changes that happen during the menstrual cycle and pregnancy due to estradiol variation. In particular, we add the polyamine drain on S-adenosyl methionine and the direct effects of estradiol on the enzymes cystathionine β-synthase (CBS), thymidylate synthase (TS), and dihydrofolate reductase (DHFR). We show that the homocysteine concentration varies inversely with estradiol concentration, discuss the fluctuations in 14 other one-carbon metabolites and velocities throughout the menstrual cycle, and draw comparisons with the literature. We then use the model to study the effects of vitamin B12, vitamin B6, and folate deficiencies and explain why homocysteine is not a good biomarker for vitamin deficiencies. Additionally, we compute homocysteine throughout pregnancy, and compare the results with experimental data. Our mathematical model explains how numerous homeostatic mechanisms in OCM function and provides new insights into how homocysteine and its deleterious effects are influenced by estradiol. The mathematical model can be used by others for further in silico experiments on changes in one-carbon metabolism during the menstrual cycle and pregnancy.
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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.