Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0030794 (
pelvic pain
)
4,056
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Endometriosis is a disease in which tissue that normally grows inside the uterus grows outside the uterus and causes chronic
pelvic pain
and infertility. However, the exact mechanisms of the pathogenesis of endometriosis-associated infertility are unknown. Epigenetic dysregulation has recently been implicated in infertility. Here, we report a reduction of
histone deacetylase 3
(
HDAC3
) protein amounts in eutopic endometrium of infertile women with endometriosis compared to a control group. To investigate the effect of
HDAC3
loss in the uterus, we generated mice with conditional ablation of
Hdac3
in progesterone receptor (PGR)-positive cells (
Pgr
cre/+
Hdac3
f/f
;
Hdac3
d/d
). Loss of
Hdac3
in the uterus of mice results in infertility due to implantation failure and decidualization defect. Expression microarray and ChIP-seq analyses identified
COL1A1
and
COL1A2
as direct targets of
HDAC3
in both mice and humans. Reduction of
HDAC3
abrogated decidualization in a primary culture of human endometrial stromal cells (hESCs) similar to that observed in infertile patients with endometriosis. Whereas attenuation of
HDAC3
resulted in p300 recruitment to
Col1a1
and
Col1a2
genes in the uterus of mice as well as hESCs, inhibition of p300 permitted hESCs to undergo decidualization. Collectively, we found attenuation of
HDAC3
and overexpression of collagen type I in the eutopic endometrium of infertile patients with endometriosis.
HDAC3
loss caused a defect of decidualization through the aberrant transcriptional activation of
Col1a1
and
Col1a2
genes in mice and
COL1A1
and
COL1A2
genes in humans. Our results suggest that
HDAC3
is critical for endometrial receptivity and decidualization.
...
PMID:Loss of HDAC3 results in nonreceptive endometrium and female infertility. 3088 66
