Identifying the key to the "Window of Receptivity" for embryo implantation
Francesco DeMayo, Ph.D., received the award for his research identifying the molecular mechanisms regulating the ability of the uterus to support embryo implantation. It has been long known through in vivo and in vitro studies that steroid hormones regulation of uterine function by regulating communication between the epithelial and stroma compartments of the endometrium. However, molecular mediator(s) for this cellular cross talk have not been elucidated. Using microarray analysis Dr. DeMayo identified the morphogen Indian hedgehog (Ihh), as progesterone regulated gene expressed in the pre-implantation mouse uterus and a potential candidate for this function. In order to investigate the role of Ihh in the uterus, Dr. DeMayo’s lab, in collaboration the lab of Dr. John Lydon, generated a new and novel mouse model which allowed for the conditional ablation of genes in female reproductive tissues. Using this innovative and experimental approach was shown to mediate the communication between the uterine epithelium and storm which is required to regulate the ability of the uterus to support embryo attachment and implantation. This research has identified the molecular mechanisms regulating the “window of receptivity” for embryo implantation. Using this approach Dr. DeMayo has opened up the field of both murine and human endometrial biology and these investigations will uncover both diagnostic and therapeutic approaches to treating women’s disease of the uterus such as infertility, endometriosis and endometrial cancer.
Dr. DeMayo’s nomination was based on the following publications:
Jeong JW, Lee KY, Kwak I, White LD, Hilsenbeck SG, Lydon JP, DeMayo FJ. Identification of murine uterine genes regulated in a ligand-dependent manner by the progesterone receptor. Endocrinology. 2005 Aug;146(8):3490-505. Epub 2005 Apr 21.
Jeong JW, Kwak I, Lee KY, White LD, Wang XP, Brunicardi FC, O'Malley BW, DeMayo FJ. The genomic analysis of the impact of steroid receptor coactivators ablation on hepatic metabolism. Mol Endocrinol. 2006 May;20(5):1138-52.
Lee K, Jeong J, Kwak I, Yu CT, Lanske B, Soegiarto DW, Toftgard R, Tsai MJ, Tsai S, Lydon JP, DeMayo FJ. Indian hedgehog is a major mediator of progesterone signaling in the mouse uterus. Nat Genet. 2006 Oct;38(10):1204-9.