| dc.description.abstract | The endometrium is the mucous lining the uterine cavity comprised of a basal and a
functional layer being the latter the one that sheds during menses and regenerates from the
basal portion. The main cell populations within the functional stratus are epithelial and
stromal cells accompanied by a variable number of leukocytes. Epithelial cells are found
covering the luminal surface and tubular glands in basal and functional layers. Endometrial
stroma contains reticular connective tissue comprised mainly by uterine fibroblasts that
rapidly differentiate into decidualized cells when stimulated by an implanting blastocyst.
The stromal compartment contains also abundant lymphocytes, granulocytes and
macrophages during luteal phase of the menstrual cycle. These cells along with epithelial
and stromal fibroblasts are source and target of paracrine signals of proliferation and
differentiation. Both components respond to ovarian steroid hormones and depend on each
other for their structure, function and responsiveness to estrogen (E2) and progesterone (P4)
(Tabibzadeh, 1998, review). During a normal menstrual cycles, human endometrium display
unique features for an adult tissue: undergoes cyclic construction and sloughing. The outer
layer of the endometrium is loss while the basal layer containing the deep glandular
epithelium gets preserved. Later on, stem cells located in this layer will originate the various
endometrial cell types in response to the appropriate hormonal stimulus, regenerating the
whole endometrium (Padykula, 1991).
The endometrial cycle is driven by the ovarian steroidal hormones and can be divided in
three phases: proliferative, secretory and menstrual. Proliferative phase lasts around 10 – 20
days averaging 14 days. During this phase, glands grow and become winding due to the
active mitosis of the epithelial cells driven by rising levels of serum E2 resulting in growing
about 10 times the original thickness of the endometrium. Indeed, extensive DNA synthesis
in epithelial cells and some in stromal cells is seen during this stage (Padykula, 1991). Once
ovulation has taken place, the increase of circulating P4 triggers the transition to the
secretory phase. During this phase, mitotic activity is inhibited and a complex secretory
activity is induced beginning with glycogen vesicles polarization in glandular epithelial
cells, locating subnuclearly which is further transported by microfilaments to the apical
region where glycogen is actively secreted to the lumen of glands. In addition, epithelial cells initiate a complex secretory activity along with the establishment of an adequate
environment for embryo implantation that take place only during a restricted time frame
called ‘window of implantation’ (Psychoyos, 1986). During this period, morphological and
molecular changes take place leading to a coordinated expression or repression of key
molecules that ultimately enable the blastocyst to attach and invade the endometrial tissue.
Such changes occur independently of the presence of a blastocyst; however the
endometrium undergoes further biochemical and morphological changes induced by signals
from the blastocyst and the following trophoblast invasion. With no embryo implantation,
the endometrium undergoes a series of processes that end toward late secretory phase with
sloughing and menses. When a successful embryo implantation takes place, luteolysis is
prevented and the endometrium is not just maintained but differentiates to decidua and
undergoes dramatic vascular changes at the implantation site. Therefore, gene expression in
the human endometrium is likely to exhibit neat and distinct changes throughout the
various stages of the menstrual cycle in accordance with the oscillations in estrogen and
progesterone serum levels and their tissue receptor levels. Since these ovarian steroid
hormones drive these processes eliciting an array of cellular and biochemical responses,
mostly through genomic pathways (O'malley & Tsai, 1992), current thinking suggests that at
the onset of receptivity, expression of some genes in given cell types of this tissue, is
temporarily turned on or increased while some others are temporarily turned off or
decreased (Tabibzadeh, 1998). Some of these changes are essential for establishing and
maintaining pregnancy. Likewise, when implantation has occurred, another program of
gene expression takes place in the endometrium, not only maintaining it, but also triggering
further differentiation to decidua and facilitating and regulating trophoblast invasion and
placenta development. The endometrium is the mucous lining the uterine cavity comprised of a basal and a
functional layer being the latter the one that sheds during menses and regenerates from the
basal portion. The main cell populations within the functional stratus are epithelial and
stromal cells accompanied by a variable number of leukocytes. Epithelial cells are found
covering the luminal surface and tubular glands in basal and functional layers. Endometrial
stroma contains reticular connective tissue comprised mainly by uterine fibroblasts that
rapidly differentiate into decidualized cells when stimulated by an implanting blastocyst.
The stromal compartment contains also abundant lymphocytes, granulocytes and
macrophages during luteal phase of the menstrual cycle. These cells along with epithelial
and stromal fibroblasts are source and target of paracrine signals of proliferation and
differentiation. Both components respond to ovarian steroid hormones and depend on each
other for their structure, function and responsiveness to estrogen (E2) and progesterone (P4)
(Tabibzadeh, 1998, review). During a normal menstrual cycles, human endometrium display
unique features for an adult tissue: undergoes cyclic construction and sloughing. The outer
layer of the endometrium is loss while the basal layer containing the deep glandular
epithelium gets preserved. Later on, stem cells located in this layer will originate the various
endometrial cell types in response to the appropriate hormonal stimulus, regenerating the
whole endometrium (Padykula, 1991).
The endometrial cycle is driven by the ovarian steroidal hormones and can be divided in
three phases: proliferative, secretory and menstrual. Proliferative phase lasts around 10 – 20
days averaging 14 days. During this phase, glands grow and become winding due to the
active mitosis of the epithelial cells driven by rising levels of serum E2 resulting in growing
about 10 times the original thickness of the endometrium. Indeed, extensive DNA synthesis
in epithelial cells and some in stromal cells is seen during this stage (Padykula, 1991). Once
ovulation has taken place, the increase of circulating P4 triggers the transition to the
secretory phase. During this phase, mitotic activity is inhibited and a complex secretory
activity is induced beginning with glycogen vesicles polarization in glandular epithelial
cells, locating subnuclearly which is further transported by microfilaments to the apical
region where glycogen is actively secreted to the lumen of glands. In addition, epithelial cells initiate a complex secretory activity along with the establishment of an adequate
environment for embryo implantation that take place only during a restricted time frame
called ‘window of implantation’ (Psychoyos, 1986). During this period, morphological and
molecular changes take place leading to a coordinated expression or repression of key
molecules that ultimately enable the blastocyst to attach and invade the endometrial tissue.
Such changes occur independently of the presence of a blastocyst; however the
endometrium undergoes further biochemical and morphological changes induced by signals
from the blastocyst and the following trophoblast invasion. With no embryo implantation,
the endometrium undergoes a series of processes that end toward late secretory phase with
sloughing and menses. When a successful embryo implantation takes place, luteolysis is
prevented and the endometrium is not just maintained but differentiates to decidua and
undergoes dramatic vascular changes at the implantation site. Therefore, gene expression in
the human endometrium is likely to exhibit neat and distinct changes throughout the
various stages of the menstrual cycle in accordance with the oscillations in estrogen and
progesterone serum levels and their tissue receptor levels. Since these ovarian steroid
hormones drive these processes eliciting an array of cellular and biochemical responses,
mostly through genomic pathways (O'malley & Tsai, 1992), current thinking suggests that at
the onset of receptivity, expression of some genes in given cell types of this tissue, is
temporarily turned on or increased while some others are temporarily turned off or
decreased (Tabibzadeh, 1998). Some of these changes are essential for establishing and
maintaining pregnancy. Likewise, when implantation has occurred, another program of
gene expression takes place in the endometrium, not only maintaining it, but also triggering
further differentiation to decidua and facilitating and regulating trophoblast invasion and
placenta development. | |
