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Mothers and Babies Research Centre, Department of Obstetrics and Gynaecology, University of Newcastle, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
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Mothers and Babies Research Centre, Department of Obstetrics and Gynaecology, University of Newcastle, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
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Mothers and Babies Research Centre, Department of Obstetrics and Gynaecology, University of Newcastle, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
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Mothers and Babies Research Centre, Department of Obstetrics and Gynaecology, University of Newcastle, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
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Mothers and Babies Research Centre, Department of Obstetrics and Gynaecology, University of Newcastle, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
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Mothers and Babies Research Centre, Department of Obstetrics and Gynaecology, University of Newcastle, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
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Mothers and Babies Research Centre, Department of Obstetrics and Gynaecology, University of Newcastle, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
Mothers and Babies Research Centre, Department of Obstetrics and Gynaecology, University of Newcastle, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
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Introduction Parturition is associated with inflammation in the fetal membranes and the decidua. Array-based studies assessing the expression of a large number of genes simultaneously as well as studies determining the expression level of
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Fetal Medicine Unit, St. George’s Hospital, London, UK
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, leading to menstruation. If a blastocyst implants successfully and pregnancy occurs, levels of progesterone remain high, the decidua is preserved and remodelling extends to the basal endometrial layer ( Brosens et al. 2002 ). Decidualisation is critical
Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China
Key Laboratory of Animal Resistance Biology of Shandong Province, College of Life Science, Shandong Normal University, Ji’nan, Shandong, China
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Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China
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Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China
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Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China
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Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China
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Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China
Key Laboratory of Animal Resistance Biology of Shandong Province, College of Life Science, Shandong Normal University, Ji’nan, Shandong, China
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and their interactions ( Johansson et al. 2011 ). Little attention has been focused on the decidua, into which the extravillous trophoblast (EVT) invades. Probably the ‘soil,’ rather than, or in addition to, the ‘seed’ is aberrant in women who
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extensive investigation of LIF–STAT and integrin signaling may improve the outcome of embryo implantation and subsequent pregnancy. In this study, we have tried to identify extracted EVs and miRNAs from decidua and decidual stromal cells. miRNA
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ABSTRACT
Progesterone-associated endometrial protein (PAEP) has been isolated from human decidualized endometrium. In-situ hybridization histochemistry was employed to determine the cellular localization of PAEP mRNA in decidua during pregnancy. PAEP mRNA was found to be expressed in the glandular epithelium of decidua spongiosa throughout pregnancy. Substantial variations in the amount of PAEP mRNA during the course of pregnancy were observed, and it was most abundant at the end of the first trimester. We also found that the PAEP gene was expressed in endometriosis and in a borderline endometrioid adenoma. As in decidual tissues, PAEP mRNA in endometriosis was abundant in the glandular compartment.
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During pregnancy, the decidua is comprised of two separate tissues located either mesometrially or antimesometrially in the uterus. Trophoblast invasion takes place only in the mesometrial decidua, where extensive angiogenesis, essential for successful implantation, occurs. Both basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) have been implicated in this phenomenon. The aim of this study was to determine whether the expression of both growth factors is intrinsic to decidua and occurs in the absence of conceptuses, whether their genes are expressed specifically in the mesometrial decidua, the site of angiogenesis, and whether both growth factors are developmentally and hormonally regulated. Decidual tissue was dissected from pseudopregnant rats and levels of both bFGF and VEGF mRNA were examined in mesometrial and antimesometrial decidua by semi-quantitative RT-PCR at different stages of pseudopregnancy. Although induction of decidualization triggered the mRNA expression of bFGF, VEGF mRNA expression remained unchanged. VEGF mRNA level was similar in both antimesometrial and mesometrial decidua, and remained constant throughout pseudopregnancy. In sharp contrast, bFGF mRNA was highly expressed in the mesometrial decidua at a time when extensive angiogenesis takes place in this tissue. Very little signal was observed in the antimesometrial decidua. To examine the regulation of these growth factors, we used a temperature-sensitive decidual cell line developed by transforming antimesometrial decidual cells with SV-40 tsA 209 mutant virus. These cells express both bFGF and VEGF mRNA. Because progesterone is necessary for decidualization and decidua secretes prolactin (PRL)-related hormones, we examined the role of these hormones on VEGF and bFGF mRNA expressions. Neither progesterone nor PRL had any effect on VEGF mRNA levels. However, bFGF mRNA expression was greatly stimulated by PRL. In conclusion, results of this investigation have revealed that bFGF, but not VEGF, mRNA becomes highly expressed in the mesometrial decidua, where angiogenesis occurs, and where trophoblasts, by invading decidual cells, may promote the release of bFGF. In addition, these results indicate that the locally secreted PRL-like hormone up-regulates the mRNA expression of bFGF.
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ABSTRACT
The presence of mRNA for epidermal growth factor (EGF) and transforming growth factor-α (TGFα) was demonstrated in small fragments of human endometrium and decidua by use of the technique of reverse transcriptase-polymerase chain reaction with nested oligonucleotide primers. The presence of mRNA encoding EGF and TGFα has not been shown in human endometrium previously. Other studies using conventional techniques, such as Northern blot or in-situ hybridization, showed the presence in low copy number of EGF but not TGFα in murine endometrium. Messenger RNA for EGF was not present in peripheral leukocytes or platelets, suggesting an endometrial source for the message. Messenger RNA for TGFα was found in these blood components, thus preventing confirmation of the source of TGFα mRNA.
Pathology Laboratory and Molecular Biology Laboratory, Istituto Auxologico Italiano, Via Zucchi, 18-Cusano Milanino, Milano, Italy
Dept of Obstetrics and Gynecology, Clinica Macedonio Melloni, University of Milano, Milano, Italy
BioXell S.p.A, Milano, Italy
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Pathology Laboratory and Molecular Biology Laboratory, Istituto Auxologico Italiano, Via Zucchi, 18-Cusano Milanino, Milano, Italy
Dept of Obstetrics and Gynecology, Clinica Macedonio Melloni, University of Milano, Milano, Italy
BioXell S.p.A, Milano, Italy
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Pathology Laboratory and Molecular Biology Laboratory, Istituto Auxologico Italiano, Via Zucchi, 18-Cusano Milanino, Milano, Italy
Dept of Obstetrics and Gynecology, Clinica Macedonio Melloni, University of Milano, Milano, Italy
BioXell S.p.A, Milano, Italy
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Pathology Laboratory and Molecular Biology Laboratory, Istituto Auxologico Italiano, Via Zucchi, 18-Cusano Milanino, Milano, Italy
Dept of Obstetrics and Gynecology, Clinica Macedonio Melloni, University of Milano, Milano, Italy
BioXell S.p.A, Milano, Italy
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Pathology Laboratory and Molecular Biology Laboratory, Istituto Auxologico Italiano, Via Zucchi, 18-Cusano Milanino, Milano, Italy
Dept of Obstetrics and Gynecology, Clinica Macedonio Melloni, University of Milano, Milano, Italy
BioXell S.p.A, Milano, Italy
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Pathology Laboratory and Molecular Biology Laboratory, Istituto Auxologico Italiano, Via Zucchi, 18-Cusano Milanino, Milano, Italy
Dept of Obstetrics and Gynecology, Clinica Macedonio Melloni, University of Milano, Milano, Italy
BioXell S.p.A, Milano, Italy
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Pathology Laboratory and Molecular Biology Laboratory, Istituto Auxologico Italiano, Via Zucchi, 18-Cusano Milanino, Milano, Italy
Dept of Obstetrics and Gynecology, Clinica Macedonio Melloni, University of Milano, Milano, Italy
BioXell S.p.A, Milano, Italy
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Pathology Laboratory and Molecular Biology Laboratory, Istituto Auxologico Italiano, Via Zucchi, 18-Cusano Milanino, Milano, Italy
Dept of Obstetrics and Gynecology, Clinica Macedonio Melloni, University of Milano, Milano, Italy
BioXell S.p.A, Milano, Italy
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Pathology Laboratory and Molecular Biology Laboratory, Istituto Auxologico Italiano, Via Zucchi, 18-Cusano Milanino, Milano, Italy
Dept of Obstetrics and Gynecology, Clinica Macedonio Melloni, University of Milano, Milano, Italy
BioXell S.p.A, Milano, Italy
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showed an increase of about 40% in 1α-OHase expression in decidua versus normal cycling endometria of both phases. To determine the cellular localization of 1α-OHase, its expression was also evaluated by immunohistochemistry. Comparable
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Transcriptional regulation of the prolactin gene in the decidua differs from that in the pituitary. Several lines of evidence strongly suggest this difference is due to regulation of the prolactin gene in the decidua and other extra-pituitary tissues by tissue-specific transcription factors, which activate distinct promoters to induce prolactin gene expression in extra-pituitary sites compared with the pituitary. The human decidua is a major site of extra-pituitary expression of the prolactin gene. Here we present evidence that the transcription factor Ets-1 is critical for basal expression of the decidua-type (or decidual) prolactin promoter. Overexpression of Ets-1 significantly induces decidual prolactin promoter activity in BeWo and JAR cells that express little or no endogenous Ets-1. Conversely, a dominant/negative mutant of Ets represses basal promoter activity. Although the proximal 1.5 kb of the decidual prolactin promoter contains six Ets motifs, only the Ets motif at nt -77/-71 is essential for basal gene expression. Mutation of the Ets motif at nt -77/-71 results in an approximately 90% decrease in promoter activity, while mutation of the other Ets motifs results in only small changes. Electrophoretic mobility shift assays demonstrate that Ets proteins in decidualized endometrial stromal cells bind this Ets motif in the decidual prolactin promoter. Ets protein expression increases up to 20-fold upon induction of decidualization in endometrial stromal cells under conditions in which expression of the prolactin gene is also induced. These studies provide strong evidence for a critical role of the Ets transcription factor in basal expression of the decidual prolactin promoter.
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ABSTRACT
While the fetal pituitary synthesizes and releases prolactin, it is also produced within the utero-placental unit during pregnancy in women and has been localized in the amnion, chorion and decidua. However, it is not clear whether prolactin is synthesized within all these non-fetal pituitary tissues. We have investigated prolactin production and its gene expression using tissue culture, immunocytochemistry and in-situ hybridization techniques. Prolactin was immunolocalized not only in the decidua but also in amnion and trophoblast cells. In contrast, the in-situ hybridization results showed that silver grains, formed by specific hybridization of a prolactin cDNA probe to prolactin mRNA, were confined to decidual cells of early and term pregnancy. The results from tissue cultures correlated well with those of in-situ hybridization, that is that only the decidua made detectable prolactin, while it was undetectable in the culture medium from trophoblast tissue, irrespective of the stage of pregnancy. This study, for the first time, establishes that only decidualized cells are involved in biosynthesis of prolactin; other prolactin-containing cells in the amnion and trophoblast appear to sequester prolactin, possibly via receptors, suggesting that prolactin may play an important paracrine role within the amnion and syncitio- and cytotrophoblast of the utero-placental unit.
