Uterine decidual response occurs in estrogen receptor-alpha-deficient mice.
Embryo-uterine interactions leading to the attachment reaction is followed by stromal cell proliferation and differentiation into decidual cells (decidualization) at the sites of blastocyst apposition. In rodents, decidualization is also induced by application of an artificial stimulus (intraluminal oil infusion) in a pseudopregnant uterus, or to one that has been appropriately prepared by exogenous progesterone (P4) and estrogen. The process of decidualization is under the control of these steroids in the presence of blastocysts or deciduogenic stimuli. Although it is well known that estrogen is required for the induction of progesterone receptors in the uterus, the functional importance of estrogen in the process of decidualization is poorly understood. To better understand the role of estrogenic actions in decidualization, we used wild-type and estrogen receptor-alpha knock-out (ERKO) mice for induction of decidualization employing a defined steroid hormonal treatment schedule. Our results demonstrate that P4 alone induces decidualization in ovariectomized wild-type or ERKO mice in response to intraluminal oil infusion in the absence of estrogen. A combined treatment of either estradiol-17beta (E2) or its catecholmetabolite 4-hydroxyestradiol-17beta(4-OH-E2) with P4 does not potentiate the decidual response produced by P4 treatment alone in either ovariectomized wild-type or ERKO mice. The induction of decidual response was associated with up-regulation of decidual cell marker genes, such as progesterone receptor, metallothionein-1, and cyclooxygenase-2. The results suggest that the stromal cell sensitivity to decidualization is critically dependent on P4-regulated events, and estrogenic induction of progesterone receptor via classical nuclear ER-alpha is not critical for this process.
Paria
B C
BC
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City 66160-7338, USA.
Tan
J
J
Lubahn
D B
DB
Dey
S K
SK
Das
S K
SK
D000818:Animals; D051546:Cyclooxygenase 2; D003656:Decidua / Q000502:physiology*; D047628:Estrogen Receptor alpha; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D007527:Isoenzymes / Q000235:genetics; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011374:Progesterone / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000235:genetics / Q000502:physiology*; D011980:Receptors, Progesterone / Q000235:genetics
D047628:Estrogen Receptor alpha; D004967:Estrogens; D007527:Isoenzymes; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011374:Progesterone; D008668:Metallothionein; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases