It is estimated that infertility affects 6.1 million American couples of childbearing age. For many of these couples, the cause of their infertility remains unclear. On a global level, infertility is believed to affect around nine percent of the female population. A recent discovery of a very small but very important molecule may offer a clue into the complex mystery of female infertility.


A study led by researchers from the Cincinnati Children’s Hospital Medical Center has identified a crucial molecular key to healthy embryo implantation and pregnancy. The gene, called Wnt5a, was found to be absolutely critical for the healthy embryo implantation in the uterus wall, according to a press release. It works along with its co-receptors ROR1 and ROR2 to help direct embryos in the right direction in order to safely make their way into the womb. Signaling from this molecule also causes uterine implantation chambers to form at regular intervals.

What It Means For Infertility, Miscarriage, and Preterm Birth

Although discovering the role of Wnt5a was exciting, it’s what happened in its absence, or when it fails, that makes this study truly groundbreaking. When signaling from the special molecule is disrupted or distorted, adverse effects such as abnormal uterine formation, and disorderly spacing of embryos and implantation result. Eventually, these side effects will go on to cause conditions such as defective decidualization, placentation, and compromised pregnancy outcomes. "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," explained senior investigator Sudhansu Dey, director of the Division of Reproductive Sciences at Cincinnati Children’s Hospital, in the press release.

Conception Is Still A Mystery

When a female egg is fertilized by a male sperm, a zygote, the earliest stage of an embryo, is formed. However, in order for the pregnancy to result in the development of a human fetus, the embryo must find its way into the uterus, where it can become implanted on the nutrient-rich uterine wall. Dey explained that as of now “it is not clearly understood what prompt embryos to move and implant within a uterine crypt with regular spacing.”

Failure To Implant

When an embryo fails to implant onto the uterine wall, a miscarriage will result. It is estimated that as many as 40 percent of pregnancies result in miscarriage, and often, this is nature’s way of selecting only the most genetically fit embryos to develop into a fetus. However, sometimes the female’s body will continue to reject perfectly healthy embryos. Other times the embryo will implant in the wrong location, such as the cervix or fallopian tubes.

Further Developments

For now, the study was only conducted on mice, but taking into consideration both the similarities and differences between mouse and human implantation, Dey still believes the discovery of Wnt5a-ROR signaling in embryo spacing could be clinically relevant. Dey and his team plan on further developing their study by uncovering the specific molecular and biochemical pathways regulated by Wnt5a-ROR signaling. However, for those of us who are not bio-molecular scientists, this simply translates as a more detailed investigation into the causes and possible solutions for human infertility.

Source: Dey SK, Cha J, Bartos A, et al. Appropriate Crypt Formation in the Uterus for Embryo Homing and Implantation Requires Wnt5a-ROR Signaling. Cell Reports. 2014.