Gene regulator sets stage for embryo implantation
Before an early embryo can implant in the uterus, a spot must be prepared for it a critical activity in which a transcriptional regulator called nuclear receptor coactivator-6 (NCOA6) plays an important role, said researchers from Baylor College of Medicine in a report that appears online in the journal Developmental Cell. This means that the NCOA6 protein has an important activity in fertility.
"NCOA6 was initially identified as a coactivator to enhance estrogen receptor function in cells cultured in laboratory," said Dr. Jianming Xu, professor of molecular and cellular biology at BCM and corresponding author of the report. However, NCOA6 has the opposite effect in live mice.
"If we have mice without this gene and its protein, then estrogen receptor activity goes up, not down as we would expect," said Xu.
In normal mice, this protein reduces uterine sensitivity to the effect of the estrogen that governs embryo implantation. However, when this protein is "knocked out," the uterus has increased estrogen sensitivity, which interferes with embryo implantation. Without NCOA6, the key receptor of estrogen in this system accumulates during the short window in which implantation is possible. The lack also causes a failure in decreasing the activity of steroid receptor coactivator 3 (SRC-3), which is a coactivator of estrogen receptor.
"Another important issue is that when you lose this protein in the uterus, estrogen sensitivity goes up," said Xu. That would seem to increase the risk of uterine cancer, another important area of study of this protein in the Xu laboratory.
Others who took part in this work include Jun Kawagoe, Qingtian Li, Paola Mussi, Lan Liao, John P. Lydon and Francesco J. DeMayo at BCM.
Funding for this work came from the National Institutes of Health (Grants CA119689, DK058242, and CA112403).