The
research focus of my group is to understand molecular events coordinating
the physiology of embryo implantation and parturition. With a basic understanding
of these processes, the long-term goal is to identify mechanism that, when
gone awry, contribute to infertility during early gestation (recurrent pregnancy
loss) or those that cause pregnancy complications prior to the natural timing
of birth (pre-term labor). Related to embryo implantation, our efforts are
aimed at identifying signaling pathways used by the embryo to modify the
uterine environment as it establishes a vascular portal for nutrient and
gas exchange. In our recent publication (Endocrinology 2007 148:4173-4184),
we established using a mouse model of pregnancy and genome-wide microarray
analysis that the embryo modulates the expression of approximately 1500
genes in the uterine endometrium prior to development of the placenta. This
occurs during a time that corresponds to the first trimester of human gestation.
We are currently working toward identifying those pathways critical for
embryo survival through functional/genetic studies involving mutant mice
deficient in expression of key components of the WNT signaling pathway.
Through our efforts we have identified a gene, called decidual restricted
gene 1 or Drg1, that exhibits an expression pattern restricted to the uterus
exclusively during early gestation. Ongoing studies are geared toward understanding
the function of Drg1 as it pertains to the establishment and maintenance
of pregnancy.
Because
of its tremendous capacity for regeneration, the female reproductive tract
makes an outstanding model to study how adult somatic stem cells maintain
tissue homeostasis and facilitate repair under natural conditions. During
the menstrual (primates) or estrous cycle (laboratory animals) the uterine
tissues undergoes natural cycles of proliferation, growth, differentiation,
deconstruction and regeneration. Using a combination of transgenic, transplantation
and molecular biology approaches, we have established that the uterus likely
harbors unique populations of adult stem cells within the stromal and epithelial
compartments. We are now working toward purification and functional characterization
of these adult stem cells, as well as elucidating the signals and pathways
that regulate the activity of these unique cells. Considering that insufficient
thickening is a major impediment establishing a successful pregnancy by
in vitro fertilization (IVF), we believe our studies of endometrial stem
cells are of potential importance to the clinic. Furthermore, through elucidation
of mechanisms that coordinate stem cell activation and subsequent tissue
growth, basic studies of uterine stem cell biology will likely have practical
application to developing therapeutic remedies for hyperproliferative diseases
of the uterus that include endometriosis and cancer. Diseases such as these
are major contributors to infertility in women.
Instructor, Department of Obstetrics, Gynecology and Reproductive Biology,
Harvard Medical School
Investigator, Vincent Center for Reproductive Biology, Massachusetts
General Hospital
Click here to email Dr. James Pru.
Click here to view a brief biographical sketch of Dr. James Pru.
