Natural estrogen and xenoestrogen mediated actions in the uterus

For more than 60 years, scientists have recognized “early” and “late” phase uterine responses to estrogen, though the mechanisms behind these changing responses remain unclear.

The general consensus is that an early event, occurring within the first 6 h, prepares the uterus for later (18-30 h) increase in DNA synthesis, cell proliferation, and protein synthesis. Our hypothesis for this project is that while early estrogenic responses are ER-independent, the late responses are ER-dependent, and a co-operation between these two phases is necessary for a full complement of growth regulation in the uterus. Our long term goals of this study are to define the genetic and epigenetic control of uterine cell proliferation and differentiation under the direction of natural estrogen and xenoestrogen. More specifically, we are currently exploring the roles of various growth regulators (such as Sik-similar protein, GPR30, Bmp8a, Fgf10, DNA methylation, and polycomb repressive complex molecules) during the progression of estrogen/xenoestrogen induced uterine growth regulation in implantation.

Cell cycle regulation of uterine stromal cell decidualization in implantation.

Endometrial stromal cells transform into morphologically and functionally specified decidual cells (decidualization), which occurs in women during the secretory phase of the menstrual cycle as well as in pregnancy, but only during pregnancy in rodents. Uterine decidualization following embryo implantation is essential for pregnancy establishment and placentation. The progression of decidualization is characterized by extensive endometrial stromal cell proliferation and differentiation throughout the decidual bed at the site of early implantation. However, the acquisition of decidual cell polyploidy, through terminal differentiation, occurs within the decidual bed only at the antimesometrial and lateral region of the implantation site. Recently, utilizing genetic mouse model has shown that polyploidy development is crucially involved with successful decidualization in early embryo implantation. The molecular mechanisms governing this program for regional decidual development remains poorly understood. In this regard, the current research specifically focuses on the roles of cMet, imprinting gene H19, and epigenetic regulation through DNA methylation and PRC1 regulators during decidual progression.