Scientists have identified a crucial molecular key to healthy embryo implantation and pregnancy in a study that may offer new clues about the medical challenges of infertility/subfertility, abnormal placentation, and placenta previa.
Multi-institutional teams conducted the study and was led by researchers at Cincinnati Children’s Hospital Medical Center.
The authors found that uterine expression of a gene called Wnt5a – a major signalling molecule in cell growth and movement in both embryo development and disease – is also critical to healthy embryo implantation in the uterus.
The scientists say that molecular signalling from Wnt5a – working in tandem with its co-receptors ROR1 and ROR2 in the uterus – causes uterine implantation chambers (crypts) in mice to form at regular intervals. The signalling also helps direct embryos to migrate in the proper direction as they settle into the womb. The authors show that disruption of appropriate uterine Wnt5a-ROR signalling leads to abnormal uterine luminal epithelial architecture, crypt formation, disorderly spacing of embryos and implantation. These adverse effects led to defective decidualisation, placentation, and ultimately compromised pregnancy outcome.
“Proper implantation is important to healthy pregnancy, and it is not clearly understood what prompts embryos to move and implant within a uterine crypt with regular spacing,” said Sudhansu K. Dey, PhD, senior investigator and director of Division of Reproductive Sciences, Cincinnati Children’s Hospital Medical Center. “If something goes wrong at this stage, there could be adverse effects throughout the course of pregnancy – whether it is subfertility, infertility, restricted growth, miscarriage or preterm birth.”
Although there are similarities and differences between mouse and human implantation, a role for Wnt5a-ROR signalling in embryo spacing could be clinically relevant, Dey said. This is because the embryo can sometimes implant close to or on the cervix (placenta previa), which can cause extensive bleeding and lead to increased mortality or morbidity for the mother and foetus. Aberrant embryo spacing may also contribute to complications in a multiple gestation pregnancy. Cincinnati Children’s Hospital