ArticleCommunications biology2022
Placental sex-dependent spermine synthesis regulates trophoblast gene expression through acetyl-coA metabolism and histone acetylation.
Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- Understanding physiological adaptations of pregnancy to the chronic hypoxia of high altitude to inform obstetrical and neonatal care.Physiological reviews · 2026Review
- Polyamine metabolism in ischemia reperfusion injury: common mitochondrial mechanisms and organ-specific differences.Journal of translational medicine · 2026Review
- The Effects of L-Citrulline on the Apparent Digestion and Metabolism of Nutrients, Blood Hormone Levels, Amino Acid Metabolism and the Diversity of Faecal Microbiota in Mares in the Later Stage of Pregnancy.Life (Basel, Switzerland) · 2026Article
- Dynamics of the Mammalian Placental Metabolome in Placentogenesis and Embryonic Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Metabolic control of feto-placental development and pregnancy outcomes.Nature reviews. Endocrinology · 2026Review
- Understanding Sex Differences in Autoimmune Diseases: Immunologic Mechanisms.International journal of molecular sciences · 2025Review
- A noncanonical role of SAT1 enables anchorage independence and peritoneal metastasis in ovarian cancer.Nature communications · 2025Article
- The role of 1-Deoxysphingolipids and Polyamines in the pathogenesis of placental syndrome.BMC pregnancy and childbirth · 2025Article
- The central role of creatine and polyamines in fetal growth restriction.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Ovarian aging: energy metabolism of oocytes.Journal of ovarian research · 2024Review
- Increased Placental sFLT1 (Soluble fms-Like Tyrosine Kinase Receptor-1) Drives the Antiangiogenic Profile of Maternal Serum Preceding Preeclampsia but Not Fetal Growth Restriction.Hypertension (Dallas, Tex. : 1979) · 2023Article
- The role of gonadal hormones and sex chromosomes in sex-dependent effects of early nutrition on metabolic health.Frontiers in endocrinology · 2023Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Placental function and dysfunction differ by sex but the mechanisms are unknown. Here we show that sex differences in polyamine metabolism are associated with escape from X chromosome inactivation of the gene encoding spermine synthase (SMS). Female placental trophoblasts demonstrate biallelic SMS expression, associated with increased SMS mRNA and enzyme activity. Polyamine depletion in primary trophoblasts reduced glycolysis and oxidative phosphorylation resulting in decreased acetyl-coA availability and global histone hypoacetylation in a sex-dependent manner. Chromatin-immunoprecipitation sequencing and RNA-sequencing identifies progesterone biosynthesis as a target of polyamine regulated gene expression, and polyamine depletion reduced progesterone release in male trophoblasts. The effects of polyamine depletion can be attributed to spermine as SMS-silencing recapitulated the effects on energy metabolism, histone acetylation, and progesterone release. In summary, spermine metabolism alters trophoblast gene expression through acetyl-coA biosynthesis and histone acetylation, and SMS escape from X inactivation explains some features of human placental sex differences.
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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.