Scientists have discovered a protein critical to the successful implantation of the embryo in the uterus. The protein is produced when high levels of estrogen are available, and enables the development of new blood cells that sustain the embryo.
The research has been conducted at numerous sites including the University of Illinois, Emory University, Baylor College of Medicine and New York University. Veterinary biosciences professor Indrani Bagchi, and co-author of the research paper said: “The formation of these new blood vessels is extremely critical for embryonic growth at this stage of pregnancy, when the embryo has begun to invade into the uterine tissue, but has yet to make a connection to the placenta where it ultimately gets its nutrients”.
This study into how estrogen drives cell differentiation and blood-vessel growth in the uterus during pregnancy is significant because it offers new explanations for early pregnancy loss and female infertility.
The protein connexin 43 (Cx43) is part of a group of proteins that regulate the flow of ions and signalling molecules between cells. This mechanism is important because the gap junction protein is instrumental in the rapid growth of new blood vessels which allow the embryo to develop and implant within the uterus.
Veterinary biosciences doctoral student Mary Laws studied the function of Cx43 in pregnant mice and in human endometrial cells. Laws deleted the protein from the chain of development, consistently causing unsuccessful embryo implantation. She said of the study: “I think this is the first animal model that shows that disruption of one particular molecule or gene leads to a defect in uterine angiogenesis.” Laws explained the impact of the protein: “Connexin 43 has been shown to be in the uterus in many animal systems – cows and pigs and rodents and humans. But this is the first time that it’s been shown to be critical for pregnancy.”
Further consideration was given to how the gap junction protein determines how cells differentiate and produce quantities of the vascular endothelial growth factor (a sub-family of growth factors involved in the formation of the embryonic circulatory system). The fact that Cx43 helps blood vessels grow, means it is a vital element of stromal tissue strength in the uterus.
Milan Bagchi, molecular and integrative physiology professor and co-author of the study added: “A fundamental aspect of female reproductive biology is how these hormones signal in uterine tissue in order to support the pregnancy.”
Continuing research goals include their aim to identify which genes are regulated by estrogen and progesterone, and determine how this effects embryo implantation in the uterine wall.