Evidence map›Paper›PMID 41933214›Full record

ArticlePediatric research2026

HIF1A, ADRB3, and VEGFA gene expression in human cord blood across gestation: insights toward a pharmacological artificial placenta.

Rosa Teresa Scaramuzzo, Lucrezia Filippini, Maura Calvani, Bianca Tirinnanzi, Stefania Crucitta, Marzia Del Re, Riccardo Morganti, Lorenza Di Marsico, Maurizio Cammalleri, Paola Bagnoli and 3 more

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Article in Pediatric research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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1 · What the graph read from it

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.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

13 authors.

Rosa Teresa ScaramuzzoNeonatology Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
Lucrezia FilippiniNeonatology Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
Maura CalvaniDepartment of Pediatric Hematology-Oncology, A. Meyer Children's Hospital IRCCS, Florence, Italy.
Bianca TirinnanziDepartment of Pediatric Hematology-Oncology, A. Meyer Children's Hospital IRCCS, Florence, Italy.
Stefania CrucittaDepartment of Pediatric Hematology-Oncology, A. Meyer Children's Hospital IRCCS, Florence, Italy.
Marzia Del ReDepartment of Faculty Medicine, Saint Camillus International University of Health and Medical Sciences, Rome, Italy.
Riccardo MorgantiSection of Statistics, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
Lorenza Di MarsicoDepartment of Biology, Unit of General Physiology, University of Pisa, Pisa, Italy.
Maurizio CammalleriDepartment of Biology, Unit of General Physiology, University of Pisa, Pisa, Italy.
Paola BagnoliDepartment of Biology, Unit of General Physiology, University of Pisa, Pisa, Italy.
Massimo Dal MonteDepartment of Biology, Unit of General Physiology, University of Pisa, Pisa, Italy.
Alessandro Pini *Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
Luca Filippi *Neonatology Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. luca.filippi@unipi.it.ORCID http://orcid.org/0000-0001-5310-9147

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRecent studies have shown that from the 23rd week of gestation onward, the fetus becomes progressively more hypoxic, with oxygenation levels rising again after 33-34 weeks. The biological significance of this biphasic oxygenation pattern has remained unclear.

methodsUmbilical cord blood samples from 100 preterm and 100 full-term neonates were analyzed for blood gas parameters and for HIF1A, ADRB3 (β3-adrenoceptor), and VEGFA gene expression.

resultsA progressive increase in mRNA expression of all three genes was observed with advancing gestational age, followed by a decline during the final weeks of pregnancy. This gene expression trend was inversely correlated with fetal oxygenation status.

conclusionThis study demonstrates that β3-adrenoceptor expression progressively increases with gestational age, supporting the concept that this receptor plays a key role in fetal development and well-being. These findings strengthen the evidence from animal models showing that pharmacological activation of β3-adrenoceptors can reproduce, even after birth, some of the beneficial effects normally provided by the intrauterine environment. Collectively, this work supports the conceptual framework for developing a "pharmacological artificial placenta" aimed at mimicking intrauterine conditions to promote physiological neonatal adaptation. IMPACT: Recent studies have shown that from the 23rd week of gestation onward, the fetus becomes progressively more hypoxic, with oxygenation levels rising again after 33-34 weeks. However, the biological significance of this biphasic oxygenation pattern had remained unclear. This study demonstrates for the first time that fetal oxygen fluctuations are accompanied by a synchronous and coordinated increase in the mRNA expression of HIF1A, ADRB3 (β3-adrenoceptor), and VEGFA genes. These findings support a mechanistic link between intrauterine hypoxia, β3-adrenergic signaling, and fetal maturation. This work contributes to ongoing research suggesting that pharmacological β3-adrenoceptor activation may help recreate intrauterine-like conditions, potentially promoting physiological fetal development in adverse environments.

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PMID41933214

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