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Accili & Arden 2004 ). Several lines of evidence suggest that one of the family members, FOXO1A (forkhead box O1A (rhabdomyosarcoma), also known as FKHD and FKH1), is involved in the regulation of human uterine decidualization. DNA microarray studies have
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ABSTRACT
Ovariectomized mice were treated with oestrogen and progesterone on a schedule to mimic early pregnancy. Decidualization was induced with oil and uteri were examined at various times after the last progesterone injection.
The first morphological change detected in the uterus of decidualized mice following withdrawal of progesterone was infiltration of leucocytes into the stroma. This preceded overt tissue breakdown and extravasation of blood cells, and did not occur following withdrawal of progesterone without decidualization. It is suggested either that there is a release of a chemoattractant from decidual cells before any morphological changes are apparent or that the signal for attracting the leucocytes is released at the time of decidual induction, but that their migration is suppressed by progesterone.
J. Endocr. (1986) 110, 93–96
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During the menstrual cycle, the ovarian hormones oestradiol and progesterone control the ordered growth and differentiation of uterine cells. This remodelling process is critical for implantation of the developing embryo, the formation of the placenta, and maintenance of pregnancy. Failure of uterine tIssues to respond appropriately to ovarian hormone signalling results in defective placentation, associated with a spectrum of pregnancy disorders such as recurrent miscarriages and preeclampsia. These obstetrical disorders are a major cause of maternal and perinatal morbidity and mortality. Progesterone exerts its action on target cells, at least in part, through binding to the progesterone receptor (PR), a member of the steroid/thyroid hormone receptor superfamily of ligand-activated transcription factors. The mechanism by which progesterone controls the differentiation of human endometrial stromal cells, a process termed decidualization, in the secretory phase of the menstrual cycle is not well understood. Emerging evidence indicates that locally expressed factors and activation of the cAMP second messenger pathway integrate hormonal inputs and confer cellular specificity to progesterone action through the induction of diverse transcription factors capable of modulating PR function.
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ABSTRACT
Pregnancy-associated endometrial α1-globulin (α1-PEG) is quantitatively the major secretory protein product, synthesized and secreted in vitro, of the human decidualized endometrium during pregnancy. This protein has been purified from cytosolic extracts of this tissue and has now been characterized as a 32 kDa somatomedin/insulin-like growth factor (IGF)-binding protein. Immunoreactive α1-PEG isolated from amniotic fluid exhibited identical physiochemical properties and IGF-I-binding characteristics. In cytosolic extracts of pregnancy endometrium, in incubation medium of this tissue and in amniotic fluid, the 32 kDa protein represented the major α1-PEG immunoreactive protein and major IGF-I-binding component. Purified α1-PEG and incubation medium of pregnancy endometrium competed for IGF-I with placental membrane IGF receptors in vitro. The implications of the endometrial source of IGF-I-binding protein are dicussed with reference to the origin of the amniotic fluid and serum small M r IGF-binding protein and to the suggested paracrine effect upon trophoblast proliferation.
J. Endocr. (1988) 118, 317–328
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ABSTRACT
Ovariectomized mice were prepared for decidualization with oestrogen and progesterone and arachis oil injected into the uterine lumen. Hormone injections were then stopped and uteri examined at intervals between 31 and 84 h after the last progesterone injection. At 31 and 35 h the stroma showed a normal decidual reaction. Between 45 and 79 h the stroma underwent a series of changes which started with the congestion of dilated blood vessels with swollen erythrocytes followed by breakdown of the vessel walls and extravasation of blood. At the same time the decidual cells showed typical apoptotic changes and there was invasion by leucocytes. An outer ring of stroma did not take part in the degenerative process and eventually a central core of blood cells and degenerating decidual cells became detached and was shed into the lumen.
Animals treated in exactly the same way but with the omission of the decidual stimulus did not show such changes in the stroma. It is suggested that the changes in the endometrium resemble those of menstruation and support the suggestion that for menstruation to occur the stroma must be differentiated for implantation. This occurs during the cycle in women but does not occur in non-primates unless a decidual stimulus is applied to the uterus.
J. Endocr. (1984) 100, 295–300
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SUMMARY
Single injections of oestriol were partially effective in sensitizing the uterus to a decidual stimulus and inducing ovum-implantation in progesterone-treated spayed mice, whereas two injections (6 h apart) were fully effective. It seems that in the progestational uterus, as in the non-progestational organ, oestriol can induce a full oestrogenic response provided that its level in the target organ is maintained. It is also concluded that ovum-implantation is not triggered by some transient early effect of oestrogen, but requires about 12 h of sustained oestrogen action for its successful completion.
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The deciduogenic action of various kinds of prostaglandin (PG), i.e. PGE1, PGE2, PGF2α and PGI2, methylated prostaglandins (15-met-PGE1, 15-met-PGE2 and 15-met-PGF2α), PGF2α-13-dehydro analogues (13-DH-PGF2α, ent-15-epi-13-DH-PGF2α), endoperoxide analogues (15S)-hydroxy-9α,11α-(epoxymethano)-prosta-5Z,13E-dienoic acid (U 44069) and (15S)-hydroxy-11α,9α-(epoxymethano)-prosta-5Z,13E-dienoic acid (U 46619), and of the prostaglandin precursor, arachidonic acid, has been demonstrated after intraluminal instillation of these compounds into the uterus of immature rats sensitized with progesterone alone. Under this minimal hormonal stimulation, in which a trauma (a scratch) of the endometrium is required to induce the decidual response, all these compounds elicited the formation of deciduomata, substantiating the suggestion that the scratch-induced decidual reaction is mediated through release of prostaglandin. Confirmation was obtained through the effect of indomethacin and cortisol, both of which decreased the decidual response brought on by a scratch or by arachidonic acid, whereas the effect of PGF2α was decreased by indomethacin but not by cortisol. Histamine, thromboxane B2, and oleic, palmitic and homo-γ-linolenic acids were not deciduogenic.
A dose-dependent inhibitory effect of indomethacin on deciduoma formation by instillation of oil into animals sensitized by progesterone plus oestradiol was also observed.
The results support the proposal that the decidual reaction involves prostaglandins and we suggest that the deciduoma is a valuable model for studying the action of prostaglandin-related compounds.
Division of Parasitology, Central Drug Research Institute, Lucknow, India
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Division of Parasitology, Central Drug Research Institute, Lucknow, India
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Division of Parasitology, Central Drug Research Institute, Lucknow, India
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Division of Parasitology, Central Drug Research Institute, Lucknow, India
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permeability, a non-genomic response of estrogen action, necessary for initiation of implantation and decidualization ( Laloraya et al. 1989 ). A role has been demonstrated for ovarian steroids, primarily estrogen, in the modulation of infiltration and
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Introduction Uterine receptivity and decidualization are critical events for the success of pregnancy in mice and humans ( Dey et al. 2004 , Cha et al. 2012 ). P4 is necessary for the establishment and maintenance of pregnancy in almost
Molecular Medicine Research Labs, Drug Discovery Research, Astellas Pharma Inc., Miyukigaoka 21, Tsukuba-shi, Ibaraki 305-8585, Japan
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Molecular Medicine Research Labs, Drug Discovery Research, Astellas Pharma Inc., Miyukigaoka 21, Tsukuba-shi, Ibaraki 305-8585, Japan
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Molecular Medicine Research Labs, Drug Discovery Research, Astellas Pharma Inc., Miyukigaoka 21, Tsukuba-shi, Ibaraki 305-8585, Japan
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Molecular Medicine Research Labs, Drug Discovery Research, Astellas Pharma Inc., Miyukigaoka 21, Tsukuba-shi, Ibaraki 305-8585, Japan
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Molecular Medicine Research Labs, Drug Discovery Research, Astellas Pharma Inc., Miyukigaoka 21, Tsukuba-shi, Ibaraki 305-8585, Japan
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another highly dynamic tissue. In rodents, the endometrial stromal cells undergo proliferation and decidualization in response to steroid hormones and blastocyst implantation at the early stage of pregnancy ( Dey et al. 2004 ). In the mammalian
