A
fresh look at three chemical mediators in endometriosis
Cytokines in the
peritoneum, progesterone resistance, chemokines in the
epithelium. What a cocktail. But each of these three
chemical mediators may have a significant role to play
in endometriosis.
Cytokines in the Peritoneum
Bedaiwy et al [1] recently
investigated the concentrations of the interleukins
IL-1 beta, IL-6, IL-8, IL-3 and tumor necrosis factor
alpha (TNF-alpha). Interleukins and TNF-alpha are a
class of biological signaling molecules called cytokines
which are responsible for the mediation of the inflammatory
response and calling for immune assistance from leukocytes,
as well as various other intercellular messages.
Bedaiwy and his team sampled the peritoneal
fluid of three categories of women. The first group
consisted of 17 women with endometriosis with ovarian
involvement, the second group was 33 women with endometriosis
without ovarian involvement, and the third group consisted
of 33 women non-patients.
Of all the compounds analysed, only
IL-8 and TNF-alpha were significantly higher in both
groups of endometriosis patients versus non-patients,
but there was no significant difference between IL-8
and TNF-alpha levels between endometriosis patient groups.
Progesterone Resistance
Burney et al [2] compared
the gene expression signatures through different phases
of the menstrual cycle in women with moderate and severe
endometriosis as well as women with no endometriosis.
The study conducted was to survey which
mRNAs were being produced during which parts of the
menstrual cycle. It was found that a woman with endometriosis
had a slightly different profile of mRNAs than non-patients.
Patients with endometriosis expressed mRNAs associated
with genes that relate to cellular survival, DNA synthesis
and mitosis. This occurred in the transition between
the proliferative phase and the secretory phase of the
uterus. The proliferative phase is the time when the
endometrium is thickening, and the secretory phase is
the time when the endometrium is prepared to receive
an embryo.
This finding is an indicator that the
cells of the endometrium of a woman with endomtriosis
are still actively multiplying long after those of a
non-patient. Progesterone is a signaler that causes
the endometrium to leave the proliferative phase, so
these findings indicate that progesterone is attenuated
in endometriosis.
While many investigators have examined
single molecules in endometrium of women with endometriosis,
this microarray study on tissue from carefully selected
subjects, confirms that there is incomplete transitioning
in endometrial gene expression from the proliferative
to the secretory phase in the eutopic endometrium of
women with endometriosis, according to a review by Lois
Salamonsen on F1000 for Medicine[3].
The authors also confirmed dysregulation
of progesterone dependent gene expression with progesterone
insensitivity in the eutopic endometrium being intrinsic
to women with endometriosis. Hence, the association
between endometriosis and infertility becomes clear:
the endometrium is not adequately prepared for implantation
in the mid-secretory phase. The study raises the question
as to whether the existence of endometriosis causes
these changes in the eutopic endometrium or whether
endometriotic lesions occur when such dysregulated endometrium
reaches ectopic sites.
Chemokines in the epithelium
Chand et al [4] analysed the
chemokines found right in the layers of the endometrium
to determine the profile of chemokines expressed in
endometriosis.
Chemokines are another sort of intercellular
signaller, belonging to the cytokine family. The study
targeted the secretory glands in the epithelium (surface
layers) of the endometrium.
Patients and non-patients submitted
samples of eutopic endometrium (the endometrium found
normally in the uterus) to be tested for comparison.
Significant results include the discovery that two chemokines,
CCL16 and CCL21 were produced in excess in the eutopic
and ectopic (misplaced) endometrium in endometriosis
as compared with non-patients. It was also found that
CCL16 was produced more abundantly in the ectopic endometrium
than in the eutopic endometrium in endometriosis. The
roles of CCL16 and CCL21 in endometriosis are not known,
so two novel molecules have been introduced into the
potential factors regulating endometriosis.
Review by: Eddie Ma
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