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The Mysteries of Implantation and Unexplained Infertility

Can unraveling the mysteries of implantation provide an explanation for unexplained infertility?

Unraveling the mysteries of implantationCan unraveling the mysteries of implantation lead to a new explanation for unexplained infertility? The early days of an embryo and its implantation are still a relative mystery to scientists. Studying this can possibly lead to answers to why a couple has difficulty getting pregnant when no other explanation exists.

Implantation is a black box

Everyone knows that a pregnancy grows in the uterus. But how does a pregnancy establish itself? Since the advent of in vitro fertilization in 1978, we have learned a great deal about fertilization and early embryo development. However, the process of normal implantation and development of the early placenta is still a mystery and remains the so-called “black box” of reproductive science and medicine.

A multi-institutional research team led by scientists at Cincinnati Children’s Hospital Medical Center recently published a paper that sheds some light on this process. A major signaling molecule for cell growth and movement was identified several years ago. This molecule is encoded by a gene called Wnt5a. It is directed by yet other cell signaling molecules made by the developing embryo. In studies using a mouse model (which is standard for embryology research since the early stages of mouse embryology mimic that of humans) the researchers found that interaction between Wnt5a and its receptors ROR1 and ROR2 are critical to normal development of the uterine lining and subsequently to normal implantation. Disruptions in these signaling pathways lead to abnormalities of implantation, including failure to establish a normal relationship between the placenta and uterine lining as well as normal spacing and/or location of implantation within the uterine cavity.

Abnormal signals at implantation may explain the failure to conceive

Why is this important for human fertility? Abnormal cell signaling pathways could explain why some women have difficulty conceiving, even if no obvious problems can be identified. It could also explain why, during in vitro fertilization cycles, some embryos fail to implant and establish a pregnancy in the uterus despite being able to grow well in the laboratory.

We are a very long way from being able to use this information to help patients clinically. But understanding what is supposed to happen normally will eventually allow us to identify, and hopefully correct, potential issues with implantation and help more couples achieve their family-building dreams.

Journal Reference: Jeeyeon Cha, Amanda Bartos, Craig Park, Xiaofei Sun, Yingju Li, Sang-Wook Cha, Rieko Ajima, Hsin-Yi Henry Ho, Terry P. Yamaguchi, Sudhansu K. Dey. Appropriate Crypt Formation in the Uterus for Embryo Homing and Implantation Requires Wnt5a-ROR Signaling. Cell Reports, 2014; DOI: 10.1016/j.celrep.2014.06.027

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