Bold claim: A single gene activated at the very start of development may hold the key to forming the placenta, the lifeline that nourishes a fetus throughout pregnancy.
Research Alerts
December 04, 2025
The placenta delivers all the nutrition, oxygen, and antibodies necessary for fetal growth during gestation. It begins forming roughly six to 12 days after conception, coinciding with the embryo implanting into the uterine lining. Failures in placental development are the second leading cause of miscarriage in early pregnancy, after fatal fetal genetic abnormalities.
Yet the earliest steps of placenta formation have long remained elusive due to ethical limits and the difficulty of studying this process in humans. In a new study, UC San Diego researchers and collaborators used human pluripotent stem cells to model how the outer cell layer—ultimately forming the placenta—develops around the embryo.
The team treated pluripotent stem cells (which can become any tissue type) with bone morphogenetic protein 4 (BMP4) to simulate early embryonic and placental differentiation.
They revealed that VGLL1 (vestigial like family member 1) is turned on at the very outset of placenta formation and plays a pivotal role in guiding pluripotent stem cells into various placental lineages. Reducing VGLL1 activity halted differentiation and blocked placental development.
Key findings about the VGLL1 protein include:
- It amplifies signaling networks across multiple pathways essential for placenta formation by partnering with another protein to regulate placenta-specific gene expression.
- It directly modulates the enzyme KDM6B (lysine-specific demethylase 6B), which helps unlock placental genes for activation.
- It, along with KDM6B, is active in the outer cell layer of the early embryo, particularly in the region associated with implantation where the placenta begins to form.
Although this work is still at the preclinical stage, it offers potential avenues to improve assisted reproductive technologies, including in vitro fertilization, in the future.
“We’re beginning to understand mechanisms that could be manipulated to increase the chances of successful embryo transfer,” said Francesca Soncin, PhD, lead contributor and corresponding author from UC San Diego School of Medicine’s Department of Pathology. “Drugs that target VGLL1 or related genes might enhance embryo quality and viability.”
The study, published November 24, 2025 in Proceedings of the National Academy of Sciences (PNAS), is accessible here: https://www.pnas.org/doi/10.1073/pnas.2508432122. The full title is “VGLL1 contributes to both the transcriptome and epigenome of the developing trophoblast compartment.”
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