Heme Oxygenase-1 Regulation in Pregnancy Pathophysiology

Heme Oxygenase-1 (HO-1) is a stress-inducible enzyme that catalyses the degradation of haem into biliverdin, free iron and carbon monoxide (CO). Through its metabolic products, HO-1 exerts potent antioxidant, anti-inflammatory and vasodilatory effects that are essential for the establishment and maintenance of pregnancy. In early gestation, HO-1 supports the invasive capacity of trophoblast cells and the reshaping of maternal spiral arteries, ensuring adequate placental perfusion. It also modulates the maternal immune response, promoting tolerance to the semi-allogeneic foetus and protecting placental tissues from oxidative damage. Dysregulation of HO-1 expression or activity is implicated in pregnancy complications such as pre-eclampsia, intrauterine growth restriction and implantation failure. Key regulators of HO-1 include the transcription factor Nrf2, hypoxia-inducible pathways and microRNA networks, while hormonal cues from oestrogen and progesterone further influence its expression. Therapeutic strategies aimed at inducing HO-1 or delivering CO donors hold promise for ameliorating disorders characterised by placental hypoxia and vascular dysfunction.

Research from Nature Portfolio

Innovative work in a rodent model of pre-eclampsia has demonstrated that nanoscale artificial oxygen carriers can directly alleviate placental hypoxia, leading to reduced levels of anti-angiogenic proteins and improved foetal growth. Administration of haemoglobin-based vesicles restored placental oxygenation, decreased circulating soluble fms-like tyrosine kinase-1 (sFlt-1) and normalised maternal blood pressure. These findings reveal a proof of concept for oxygen-mediated therapies that target the HO-1/CO axis indirectly by correcting the hypoxic environment that underpins aberrant vessel remodelling and oxidative stress in pregnancy complications.

Heme Oxygenase-1 Regulation in Pregnancy Pathophysiology publication trend

The graph below shows the total number of articles in heme oxygenase-1 regulation in pregnancy pathophysiology across all publications each year (not limited to Nature Index journals).

Technical terms

Heme Oxygenase-1 (HO-1): An enzyme that degrades haem into biliverdin, free iron and carbon monoxide, providing antioxidant and cytoprotective effects.

Trophoblast: The specialised cell layer of the embryo that invades the maternal uterine lining to form and maintain the placenta.

Spiral artery remodelling: The process by which maternal uterine arteries are transformed by trophoblast invasion to increase blood flow to the developing placenta.

sFlt-1: A soluble form of the VEGF receptor that sequesters vascular growth factors, acting as an anti-angiogenic mediator in pregnancy disorders.

References

1. Artificial oxygen carriers rescue placental hypoxia and improve fetal development in the rat pre-eclampsia model. Scientific Reports (2015).
2. Absence of Heme Oxygenase-1 Affects Trophoblastic Spheroid Implantation and Provokes Dysregulation of Stress and Angiogenesis Gene Expression in the Uterus. Cells (2024).
3. Exposure to a Low-Oxygen Environment Causes Implantation Failure and Transcriptomic Shifts in Mouse Uteruses and Ovaries. Biomedicines (2024).
4. HMOX1 is partly responsible for phenotypic and functional abnormalities in mesenchymal stem cells/stromal cells from placenta of preeclampsia (PE) patients. Stem Cell Research & Therapy (2020).