Researchers uncover the earliest stages of human placenta formation

A gene that turns on very early in embryonic development could be key to the formation of the placenta, which provides the developing fetus with what it needs to thrive during gestation.

The placenta provides all of the nutrition, oxygen and antibodies that a developing human fetus needs to thrive throughout gestation. The temporary organ begins to form within six to 12 days after conception, just as the embryo implants itself in the lining of the uterus. Failure of the placenta to form correctly is the second leading cause of miscarriage during early pregnancy, after genetic abnormalities of the fetus that are incompatible with life.

However, the initial stages of placental formation have remained a mystery due to ethical considerations and technical constraints on studying the process in humans.

How researchers modeled placental development

In a new study, University of California San Diego researchers and their colleagues report overcoming these challenges by using human pluripotent stem cells to model the formation of the outer layer of cells around an embryo that eventually forms the placenta.

The study is published in PNAS.

The team treated the pluripotent stem cells—which can develop into any type of tissue in the body—with a signaling protein called BMP4 (bone morphogenetic protein 4) in order to mimic cell differentiation in early development of the embryo and placenta.

The role of VGLL1 in placenta formation

They discovered that a gene called VGLL1 (vestigial like family member 1) was turned on very early during placenta formation. It was key to the process of turning pluripotent stem cells into various types of placental stem cells; when the researchers decreased VGLL1 activity, the stem cells ceased to differentiate, halting placental development.

The researchers found that the VGLL1 protein:

• Boosted signaling networks in multiple pathways important for placenta formation by coordinating with another protein to regulate placenta-specific gene expression.
• Directly regulated an enzyme called KDM6B (lysine-specific demethylase 6B ) that “unlocks” placental genes so they could be activated.
• Was active, along with KDM6B, in the outer layer of the early embryo, especially in the area involved in implantation where the placenta forms.

Potential implications for fertility treatments

While the research is still in the  preclinical stages, the findings could potentially contribute to improving the success of in vitro fertilization in the future.

“We’ve started to understand mechanisms that we might be able to manipulate to ensure successful transfer of embryos, for example,” said lead contributor and corresponding author Francesca Soncin, assistant professor in the Department of Pathology at UC San Diego School of Medicine.

“Drugs that target VGLL1 or related genes could also be used to improve the quality and viability of the embryo.”