Molecular signaling in early placenta formation gives clues to causes of pregnancy complications

April 16, 2013

Understanding the molecular control of placenta formation, the organ which enables fetal growth, is critical in diagnosing and treating related pregnancy complications. A group of scientists at the Chinese Academy of Sciences, Beijing, China, and the University of Calgary, Canada has revealed a molecular feedback loop that governs the earliest steps of placenta formation in mice, which is known to mimic placenta formation in humans. Their findings are published April 16 in the open access journal PLOS Biology.

The earliest steps of placenta formation involve the development of the labyrinthine layer, which comprises a convoluted that sits between the maternal and fetal blood vessels, facilitating the exchange of nutrients, gases, and wastes between the mother and fetus. Normal development of the labyrinthine layer involves the folding of a flat sheet of trophoblast cells (originally the outer layer of the very primitive embryo) into finger-like projections called villi, which go on to branch out, under developmentally controlled signaling, into a cavity where maternal blood circulates.

Previous studies have identified a transcription factor, Gcm1, that plays a key role in this process, and in the formation of a functional labyrinthine layer. However, the signals that trigger and maintain the initial Gcm1 pattern have to date been unresolved.

In the new research, groups led by Drs. Haibin Wang and James C. Cross found that the deletion of a Wnt receptor, Frizzled5, led to placental defects in mice that were similar to the defects observed when they were devoid of Gcm1. Wanting to identify the consequences of these defects on labyrinthine development, the research groups found that a positive operates between Gcm1 and Fzd5 that is essential for the normal folding and branching actions of the trophoblast sheet. Specifically, they showed that Gcm1 upregulates Fzd5 at branching sites, and in turn this elevated Fzd5 expression maintains the Gcm1 expression.

The researchers also found that the Fzd5-Gcm1 mediated signaling triggers the breaking of cell junctions between the trophoblast cells—a step that is known to be pivotal for initiating this 'branching' process. In addition, they found that Fzd5-mediated signaling upregulated the expression of a certain growth factor known to stimulate blood vessel growth, therefore potentially attracting fetal vessel invasion of the branching villi.

Finally, and with implications for human disease, the researchers demonstrated that this Gcm1-Fzd5 mediated signaling cascade also occurs in human trophoblast cells that are undergoing this same differentiation process in the laboratory.

"We provide here genetic, molecular, pharmacological, and physiological evidence that an amplifying feedback loop between Gcm1 and Fzd5 is essential for normal placental development of mice." said Dr. Wang. "Besides shedding light on the fundamental mechanisms of branching morphogenesis during mouse placental development, the finding has high clinical relevance, since the Gcm1-Fzd5 signaling cascade also operates in human trophoblasts, and when its regulation goes wrong, it can be linked to trophoblast-related diseases, such as preeclampsia."

Explore further: New molecular pathway regulating angiogenesis may fight retinal disease, cancers

More information: Lu J, Zhang S, Nakano H, Simmons DG, Wang S, et al. (2013) A Positive Feedback Loop Involving Gcm1 and Fzd5 Directs Chorionic Branching, Morphogenesis in the Placenta. PLoS Biol 11(4): e1001536. doi:10.1371/journal.pbio.1001536

Related Stories

Study implicates marijuana use in pregnancy problems

September 12, 2012

New research indicates marijuana-like compounds called endocannabinoids alter genes and biological signals critical to the formation of a normal placenta during pregnancy and may contribute to pregnancy complications like ...

Recommended for you

We've all got a blind spot, but it can be shrunk

August 31, 2015

You've probably never noticed, but the human eye includes an unavoidable blind spot. That's because the optic nerve that sends visual signals to the brain must pass through the retina, which creates a hole in that light-sensitive ...

Biologists identify mechanisms of embryonic wound repair

August 31, 2015

It's like something out of a science-fiction movie - time-lapse photography showing how wounds in embryos of fruit flies heal themselves. The images are not only real; they shed light on ways to improve wound recovery in ...

New 'Tissue Velcro' could help repair damaged hearts

August 28, 2015

Engineers at the University of Toronto just made assembling functional heart tissue as easy as fastening your shoes. The team has created a biocompatible scaffold that allows sheets of beating heart cells to snap together ...

Research identifies protein that regulates body clock

August 26, 2015

New research into circadian rhythms by researchers at the University of Toronto Mississauga shows that the GRK2 protein plays a major role in regulating the body's internal clock and points the way to remedies for jet lag ...

Fertilization discovery: Do sperm wield tiny harpoons?

August 26, 2015

Could the sperm harpoon the egg to facilitate fertilization? That's the intriguing possibility raised by the University of Virginia School of Medicine's discovery that a protein within the head of the sperm forms spiky filaments, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.