Mechanisms of decidualization

Christian, Mark; Mak, Ian; White, John O.; Brosens, Jan J.

doi:10.1016/s1472-6483(12)60112-6

Cited by 32 publications

(17 citation statements)

References 57 publications

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“…Subsequent siRNA depletion studies revealed that the transcription factor FOXO1 is also central to the induction of the decidual programme (Grinius et al 2006). The expression of FOXO1 in mid-secretory endometrium coincides with that of several other transcriptional regulators of the decidual process, including p53, STAT5 and C/EBPb (Christian et al 2002a,b,c, Mak et al 2002, Pohnke et al 2004. Moreover, many of these factors are capable of physically interacting with the activated PR and regulate PRL expression by binding to a discrete region in the proximal decidual-specific promoter that contains overlapping FOXOand C/EBPb-DNA binding sites as well as PR response element half-sites.…”

Section: Foxo Transcription Factors In Cycling Endometriummentioning

confidence: 97%

The diversity of sex steroid action: the role of micro-RNAs and FOXO transcription factors in cycling endometrium and cancer

Lam¹,

Shah²,

Brosens³

2011

Journal of Endocrinology

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The rise and fall in ovarian oestrogen and progesterone production orchestrates a series of events that are indispensable for reproduction, including ovulation, implantation, decidualisation and menstruation. In the uterus, these events involve extensive tissue remodelling, characterised by waves of endometrial cell proliferation, differentiation, recruitment of inflammatory cells, apoptosis, tissue breakdown, menstruation and regeneration. The ability of ovarian hormones to trigger such diverse physiological responses is foremost dependent upon interaction of activated steroid receptors with specific transcription factors, such as Forkhead box class O (FOXO) proteins, involved in cell fate decisions. Furthermore, micro-RNAs (miRNAs), small non-coding RNAs that function as posttranscriptional regulators of gene expression, have emerged as a major regulator system of steroid hormone responses in the female reproductive tract. Consequently, increasing evidence shows that deregulated uterine miRNA expression underpins a spectrum of common reproductive disorders, ranging from implantation failure to endometriosis. Furthermore, by targeting FOXO transcription factors and other key regulators of tissue homeostasis, oncogenic endometrial miRNAs promote tumourigenesis and cancer progression.

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Section: Foxo Transcription Factors In Cycling Endometriummentioning

confidence: 97%

The diversity of sex steroid action: the role of micro-RNAs and FOXO transcription factors in cycling endometrium and cancer

Lam¹,

Shah²,

Brosens³

2011

Journal of Endocrinology

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“…In human pregnancy, decidualization extends to the basalis endometrium and is a critical regulator of placental development and trophoblast invasion (74). Recent evidence suggests that paracrine cross-talk between the glands and stroma may be needed for optimal stromal cell decidualization (75).…”

Section: On Gd 35 Induces the Expression Of Lif In The Glands Of Thementioning

confidence: 99%

Forkhead box a2 (FOXA2) is essential for uterine function and fertility

Kelleher

Wang

Pru

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

130

177

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Establishment of pregnancy is a critical event, and failure of embryo implantation and stromal decidualization in the uterus contribute to significant numbers of pregnancy losses in women. Glands of the uterus are essential for establishment of pregnancy in mice and likely in humans. Forkhead box a2 (FOXA2) is a transcription factor expressed specifically in the glands of the uterus and is a critical regulator of postnatal uterine gland differentiation in mice. In this study, we conditionally deleted FOXA2 in the adult mouse uterus using the lactotransferrin Cre (Ltf-Cre) model and in the neonatal mouse uterus using the progesterone receptor Cre (Pgr-Cre) model. The uteri of adult FOXA2-deleted mice were morphologically normal and contained glands, whereas the uteri of neonatal FOXA2-deleted mice were completely aglandular. Notably, adult FOXA2-deleted mice are completely infertile because of defects in blastocyst implantation and stromal cell decidualization. Leukemia inhibitory factor (LIF), a critical implantation factor of uterine gland origin, was not expressed during early pregnancy in adult FOXA2-deleted mice. Intriguingly, i.p. injections of LIF initiated blastocyst implantation in the uteri of both gland-containing and glandless adult FOXA2-deleted mice. Although pregnancy was rescued by LIF and was maintained to term in uterine gland-containing adult FOXA2-deleted mice, pregnancy failed by day 10 in neonatal FOXA2-deleted mice lacking uterine glands. These studies reveal a previously unrecognized role for FOXA2 in regulation of adult uterine function and fertility and provide original evidence that uterine glands and, by inference, their secretions play important roles in blastocyst implantation and stromal cell decidualization.T he uterus is comprised of two tissue compartments, the endometrium and the myometrium. The endometrium contains three cell types, luminal epithelium (LE), glandular epithelium (GE), and stroma. In mice, the uterus becomes receptive to blastocyst implantation on gestational day (GD) 4 (with the observation of a postcoital vaginal plug designated GD 0.5); it is prereceptive on GD 1-3, and by the afternoon of GD 5 it becomes nonreceptive (refractory) (1-3). Dynamic changes in ovarian estrogen and progesterone production act via the uterus to regulate uterine receptivity, blastocyst implantation, and stromal cell decidualization necessary for the establishment of pregnancy (4-6). The implantation process, which is initiated by the attachment of the blastocyst trophectoderm to the receptive LE, occurs before or right after midnight in the evening of GD 4 and becomes more prominent by the morning of GD 5. By GD 6, the trophectoderm begins to contact directly stromal cells that then begin to differentiate into decidual cells, which are required for successful pregnancy because they regulate placental development and local maternal immune responses (7,8).The infertility observed in leukemia inhibitory factor (Lif)-null mice and uterine gland-knockout (UGKO) mice and sheep established ...

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“…(A) Morphology of human ESCs cultured in the absence or presence of relaxin (100 ng/mL) and/or the PDE4 inhibitor rolipram (100 μM) for 2 days. At this time, the cultures show maximum divergence in the progression of in vitro decidualization, as indicated by the typical polygonal cobblestone appearance of the cells, as described in detail elsewhere 3. Unstimulated cells retain their relatively undifferentiated fusiform shape (control).…”

Section: Resultsmentioning

confidence: 81%

“…In light of the observed synergistic cooperation between relaxin stimulation and PDE inhibition to generate a persistent cAMP response, a similar pharmacological approach was used to test whether this synergy indeed promotes the decidualization phenotype in vitro . Decidualization is defined by the profound transformation of the elongated fibroblast‐like phenotype of the endometrial stromal cell to the larger polygonal phenotype of the decidual cell 3. Simultaneously, there is an induction of decidual prolactin and IGF‐BP1 gene transcription 4,5.…”

Section: Resultsmentioning

confidence: 99%

“…Decidualization of the endometrial stroma is crucial for successful embryo implantation and maintenance of pregnancy. This profound differentiation process is defined by a marked phenotypic change in stromal cell shape, with the elongated fibroblast‐like cells typical of the proliferative phase acquiring the larger polygonal phenotype characteristic of the decidual cell 3. At the molecular level, decidualization is characterized by the onset of decidual prolactin and insulin‐like growth factor binding protein‐1 (IGF‐BP1) production 4,5…”

Section: Introductionmentioning

confidence: 99%

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Relaxin and Phosphodiesterases Collaborate during Decidualization

Bartscha¹,

Ivell

2004

Annals of the New York Academy of Sciences

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During the evolution of mammals, the endometrium has developed for one reason only: to implant an embryo in the uterus. In higher primates, should an oocyte fail to be fertilized, then the endometrial layer is sloughed off during menses and the menstrual cycle starts again with a new round of endometrial differentiation. This stromal differentiation process is called decidualization and is accompanied in vivo by sustained high levels of intracellular cAMP. The present study was conducted to determine whether manipulation of cAMP-phosphodiesterase (PDE) activities in cultured human endometrial stromal cells could positively influence the decidualization process. The combination of relaxin treatment with inhibition of PDE4 by the specific inhibitor rolipram induced a strong increase in relaxin-mediated cAMP production, both acutely, after 20 min, and after long-term treatment for 3 days, to promote a sustained intracellular cAMP concentration. Moreover, there was a dramatic synergistic effect on the decidualization phenotype, characterized both morphologically and by increased production of prolactin and insulin-like growth factor binding protein-1 gene transcripts. The observations that expression of PDE4D transcripts were selectively increased by cAMP and that inhibition of protein kinase A by H89 to potentially block negative feedback regulation enhanced the relaxin/rolipram-mediated cAMP accumulation lead to a complex picture of cAMP regulation in these cells. There appears to be a coordinated contribution by relaxin and PDE4 at different levels to promote a sustained increased cAMP concentration during decidualization, and thus to provide an adequate maternal interface for the implanting blastocyst.

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Mechanisms of decidualization

Cited by 32 publications

References 57 publications

The diversity of sex steroid action: the role of micro-RNAs and FOXO transcription factors in cycling endometrium and cancer

The diversity of sex steroid action: the role of micro-RNAs and FOXO transcription factors in cycling endometrium and cancer

Forkhead box a2 (FOXA2) is essential for uterine function and fertility

Relaxin and Phosphodiesterases Collaborate during Decidualization

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