Academic Journal
Early Peri-conceptional Alcohol Exposure before Implantation Disrupts Placental Development across Gestation.
| Τίτλος: | Early Peri-conceptional Alcohol Exposure before Implantation Disrupts Placental Development across Gestation. |
|---|---|
| Συγγραφείς: | Cortes DRE; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA.; Animal Imaging Core, Rangos Research Center at UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA., West D; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Coulson NW; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Hartwick S; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Animal Imaging Core, Rangos Research Center at UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA., Becker-Szurszewski T; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Animal Imaging Core, Rangos Research Center at UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA., Stapleton MC; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Saladino GM; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Simmons JL 3rd; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Sferruzzi-Perri AN; Department of Physiology, Development & Neuroscience, University of Cambridge, UK., Kohanbash G; Department of Neurosurgery, University of Pittsburgh, Pittsburgh, PA, USA. Pittsburgh, PA, USA., Sneiderman C; Department of Neurosurgery, University of Pittsburgh, Pittsburgh, PA, USA. Pittsburgh, PA, USA., Chandran U; Department of Bioinformatics, University of Pittsburgh, Pittsburgh, PA, USA., Wang J; Department of Bioinformatics, University of Pittsburgh, Pittsburgh, PA, USA., Cristancho AG; Department of Neurology, Perelman School of Medicine, University of Pennsylvania, PA, USA.; Division of Child Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., McKennan CG; Department of Statistics, University of Pittsburgh, Pittsburgh, PA, USA., Cerqueira DM; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Ho J; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Bharathi S; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Goetzman ES; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Chaillet JR; Department of Obstetrics, Gynecology & Reproductive Sciences, University of Pittsburgh., Christodoulou AG; Department of Radiological Sciences, David Geffen School of Medicine, at UCLA, Los Angeles, CA, USA.; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA., Wu YL; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA.; Animal Imaging Core, Rangos Research Center at UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA. |
| Πηγή: | Research square [Res Sq] 2026 Aug 14. Date of Electronic Publication: 2026 Aug 14. |
| Τύπος έκδοσης: | Journal Article; Preprint |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Country of Publication: United States NLM ID: 101768035 Publication Model: Electronic Cited Medium: Internet ISSN: 2693-5015 (Electronic) Linking ISSN: 26935015 NLM ISO Abbreviation: Res Sq Subsets: PubMed not MEDLINE |
| Περίληψη: | Fetal Alcohol Spectrum Disorder, caused by prenatal alcohol exposure, remains a major public health concern, affecting up to 1 in 20 U.S. schoolchildren. As pregnancy is typically not recognized until five to six weeks of gestation, alcohol exposure often occurs unknowingly during the peri-conceptional period, a highly vulnerable developmental window of oocyte maturation, preimplantation and peri-implantaion. During this period, rapid cellular divisions precede lineage specification and organogenesis, rendering the conceptus sensitive to environmental insults such as alcohol. The placenta is increasingly recognized as an active mediator of alcohol-induced neurodevelopmental risk through the placenta-brain axis. We characterize peri-conceptional alcohol (PCA) exposure on placental development in a mouse PCA model mimicking human drinking patterns. Single-cell transcriptomic analyses on late gestation (embryonic day E17.5) placentas revealed disruption of extracellular matrix and collagen remodeling pathways within the labyrinth, processes essential for placental vascular development and mitochondrial dysfunction. Mitochondria isolated from E17.5 placentas showed compromised respiration and oxygen consumption. We assess placental vascular and hemodynamic functions with non-invasive dynamic contrast-enhanced MRI (DCE-MRI), enabling analysis across placental compartments for longitudinal evaluation of perfusion, substrate delivery, and contractile function. We demonstrate that PCA exposure arrests placental vascularization, perfusion, and morphological maturation, with PCA-exposed placentas at E17.5 resembling naïve placentas at E14.5. PCA exposure before implantation altered long-term placental programming, resulting in impaired placental perfusion and mitochondrial functions across gestation. These findings implicate placental dysfunction as a critical mechanism in Fetal Alcohol Spectrum Disorder pathogenesis and identify extracellular matrix remodeling and mitochondria as potential therapeutic targets following PCA exposure. |
| Competing Interests: | Competing Interests Statement The authors have no conflicts of interests to declare. |
| Contributed Indexing: | Keywords: FASD; MRI; fetal alcohol spectrum disorder; perfusion; placenta |
| Entry Date(s): | Date Created: 20261008 Date Completed: 20261018 Latest Revision: 20261018 |
| Update Code: | 20261018 |
| PubMed Central ID: | PMC13640925 |
| DOI: | 10.21203/rs.3.rs-10319561/v1 |
| PMID: | 42845570 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2693-5015 |
|---|---|
| DOI: | 10.21203/rs.3.rs-10319561/v1 |