AsianScientist (Oct. 28, 2025) – Every new pregnancy balances on the success of a fertilized egg to implant—latching on and burrowing into the lining of the uterus. This multi-step, synchronized process is often the weakest link in human reproduction.
Over half the embryos in assisted reproductive procedures like in vitro fertilization (IVF), fail at the implantation stage, and around 15 percent of those that do attach end in miscarriage. Modern fertility treatments can only assist so much without scientists being able to observe and understand this event, which normally takes place deep within mammalian tissues.
“Previous studies have used model embryos, created from stem cells, to emulate embryonic development pre- and post-implantation,” said Takehiro Hiraoka, a visiting professor at the Department of Obstetrics and Gynecology at the University of Tokyo in Japan. “However, without the uterus, they cannot genuinely replicate embryo implantation, and studies have been unable to recreate this process.”
Now, researchers led by Hiraoka at the University of Osaka have found a way to keep mouse uterine tissue alive outside the body. In their study published in Nature Communications, the method was able to capture the key stages of embryo implantation, marking an important milestone in studying reproductive biology.
To authentically reenact the complex communication between the embryo and the different uterine cells, the scientists cultured small pieces of mice endometrium rather than relying on artificial models. They used an air-liquid interface (ALI) culture system—a method where the tissue is partly exposed to air and partly to liquid nutrients—and built custom devices made of a gas-permeable material called PDMS to control oxygen delivery.
By testing and tweaking the system, the team found an optimal setting for embryo attachment. It allowed over 90 percent of the embryos to fix onto the uterine tissue under 24 hours. After 48 hours, about 85 percent remained attached and continued developing distinct cell layers typical of embryos around day five of natural pregnancy.
Gene expression profiling and microscopic analysis showed that the embryo-uterus interactions and cellular changes closely mimicked those seen during implantation in live mice.
Importantly, the scientists spotted the activation of COX-2, a maternal enzyme that regulates implantation at sites where the embryos contacted the uterine tissue. Blocking COX-2 disrupted embryo attachment and affected the activity of AKT, an embryonic protein vital for supporting cell growth and placenta formation.
“Further experiments indicated that introducing an activated form of AKT into embryos recovered defective implantation that was triggered by maternal COX-2 inhibition,” said senior author Masahito Ikawa, a professor at the University of Osaka. “We were thus able to find a potential way to overcome the issue of implantation failure, indicating the strong potential of our technique for improving assisted reproduction in the future.”
The team envisions adopting their technology in IVF clinics, where endometrial biopsies are already routine. Modelling implantation using patient-derived uterine tissues could become a valuable tool for understanding why embryos fail to implant and for developing therapies to overcome these hurdles.
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Source: University of Osaka; Photo: Shutterstock
This article can be found at An ex vivo uterine system captures implantation, embryogenesis, and trophoblast invasion via maternal embryonic signaling.
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