The use of assisted reproductive technologies like in vitro fertilization (IVF) is growing more widespread globally. However, despite successful embryo creation, over half of all embryos are lost due to failed uterine implantation.
A new study published in Nature Communications introduces a method for investigating embryonic implantation in mice using uterine tissue outside the body (ex vivo), with hopes that this will lead to improved human implantation rates.
Nature CommunicationsThe researchers faced the challenge of observing deep tissues in a living uterine environment. This led them to explore whether they could keep part of the uterus alive externally, allowing for observation of the implantation process unattained before.
"Previous research used model embryos derived from stem cells to simulate embryonic development before and after implantation," said lead author Takehiro Hiraoka.
"But without the uterus, they couldn't accurately replicate embryo implantation. Research has yet to successfully recreate this complex process."
By using a specialized culture method that positions mouse uterine tissue between liquid and gas surfaces on either side, researchers could place embryos onto small pieces of endometrium. They then monitored how embryos implanted and developed.
Their technique achieved over 90% implantation success, resulting in embryo development and invasion of the uterine lining by the embryo.
Nature Communications"We noticed specific features typical of what transpires during internal implantation," noted senior author Masahito Ikawa. "For instance, COX-2, a key maternal implantation regulator, was induced at the site of embryonic attachment."
To demonstrate their system's potential, the research team investigated COX-2 induction pathways and discovered that embryonic AKT - a protein crucial for placental formation and cellular survival - was affected by maternal COX-2.
"Further experiments revealed that introducing an activated form of AKT into embryos rescued defective implantation triggered by maternal COX-2 inhibition," confirmed Ikawa.
"This indicates our technique's promise in addressing implantation failure, offering strong potential for enhancing assisted reproduction in the future."
Despite remaining challenges, like maintaining embryo development past day 5.5, results are encouraging. With further method improvements, this technique could develop treatments for recurrent implantation failures and boost rates of assisted reproductive technologies.
This advancement may give hope to families with previously untreatable conditions who dream of having a child.