Pediatr Res. 2026 Apr 3. doi: 10.1038/s41390-026-04879-8. Online ahead of print.
ABSTRACT
BACKGROUND: 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. The biological significance of this biphasic oxygenation pattern has remained unclear.
METHODS: Umbilical 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.
RESULTS: A 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.
CONCLUSION: This 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.
PMID:41933214 | DOI:10.1038/s41390-026-04879-8
