Bold claim: researchers at UC San Diego are revealing the very first steps of how the human placenta forms, shedding light on a process that has long resisted easy study.
Research Alert
A gene that activates at the earliest moments of embryonic development may hold the key to placenta formation, the lifeline that supplies a growing fetus with nutrients, oxygen, and antibodies throughout pregnancy. The placenta begins to form about six to twelve days after conception, precisely when the embryo embeds into the uterine lining. When placental development goes awry, pregnancy loss is often linked to this failure—second only to fatal fetal genetic abnormalities as a cause of miscarriage in early gestation.
Yet the initial phases of placental development have remained largely elusive due to ethical boundaries and the technical challenges of studying this stage in humans. In a groundbreaking approach, the UC San Diego team and collaborators modeled placental formation by using human pluripotent stem cells to recreate the outer cell layer that eventually becomes the placenta.
To simulate early embryonic differentiation, the researchers exposed these versatile stem cells—capable of becoming any cell type—to BMP4, a signaling protein that drives early development toward placental cell fates.
Their experiments highlighted VGLL1 (vestigial like family member 1) as an extremely early-acting gene essential for placental lineage specification. Reducing VGLL1 activity halted differentiation, effectively stalling placental development.
Key findings about VGLL1 include:
- It enhances signaling across multiple pathways that guide placenta formation by coordinating with a partner protein to control placenta-specific gene expression.
- It directly regulates the enzyme KDM6B (lysine-specific demethylase 6B), which unlocks placental genes so they can be activated.
- VGLL1 and KDM6B activity was observed in the outer cell layer of the early embryo, particularly in the region responsible for implantation where the placenta originates.
Although these results stem from preclinical models, they hint at potential avenues to improve outcomes in assisted reproductive technologies in the future.
“We’re beginning to map mechanisms that might be manipulated to increase the likelihood of successful embryo transfer,” said Francesca Soncin, the study’s lead contributor and corresponding author, and an assistant professor in the Department of Pathology at UC San Diego School of Medicine. “Drugs targeting VGLL1 or related genes could someday enhance embryo quality and viability.”
The work was published on November 24, 2025 in Proceedings of the National Academy of Sciences (PNAS). See the full study titled “VGLL1 contributes to both the transcriptome and epigenome of the developing trophoblast compartment,” available here: http://www.pnas.org/doi/10.1073/pnas.2508432122.
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