scholarly journals Gain-of-function β-catenin in the uterine mesenchyme leads to impaired implantation and decidualization

2017 ◽  
Vol 233 (1) ◽  
pp. 119-130 ◽  
Author(s):  
Amanda L Patterson ◽  
Jamieson Pirochta ◽  
Stephanie Y Tufano ◽  
Jose M Teixeira
Keyword(s):  
Epithelial Cell ◽  
Early Pregnancy ◽  
Embryo Implantation ◽  
Junctional Complex ◽  
Mullerian Duct ◽  
Mesenchymal Tumors ◽  
Gain Of Function ◽  
Müllerian Duct ◽  
Duct Development

Embryo implantation and endometrial decidualization are critical events that occur during early pregnancy in humans and mice, and perturbation in either can result in infertility. WNT signaling through the canonical β-catenin pathway plays a pivotal role in embryonic Müllerian duct development, postnatal uterine maturation and establishment of pregnancy. Loss of β-catenin in the Müllerian duct mesenchyme (MDM)-derived stroma and myometrium results in impaired decidualization and infertility, whereas gain-of-function (GOF) results in the formation of mesenchymal tumors and sub-fertility attributed to malformed oviducts. We hypothesized that GOF β-catenin further contributes to sub-fertility through improper stromal and epithelial cell signaling during embryo implantation and decidualization. We show that mice with GOF β-catenin in MDM-derived stroma and myometrium have reduced implantation sites after embryo transfer and decreased decidualization. On day 4.5 of pseudopregnancy or in mice treated with progesterone and estrogen to mimic early pregnancy, the estrogen–LIF–ERK and progesterone–IHH pathways remain predominantly intact in GOF β-catenin mice; however, JAK/STAT signaling is altered. pSTAT3 is significantly reduced in GOF β-catenin mice and expression of downstream epithelial junctional complex factors, Ctnna1 and Cldn1, is increased. We also show that purified stromal cells from GOF β-catenin uteri, when removed from epithelial cell influence and provided with the appropriate hormonal stimuli, are able to decidualize in vitro indicating that the cells are intrinsically capable of decidualization. Taken together, these results suggest that dysregulated β-catenin activity in the stroma affects epithelial cell STAT3 signaling and ultimately embryo implantation and stromal decidualization.

YY1 and RTCB in mouse uterine decidualization and embryo implantation

Reproduction ◽  
2021 ◽  
Author(s):  
Ran Li ◽  
Xiao-Tong Song ◽  
Si-Wei Guo ◽  
Na Zhao ◽  
Mei He ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
Embryo Implantation ◽  
Mrna Splicing ◽  
Proximal Promoter ◽  
Mouse Uterus ◽  
Rna Ligase ◽  
Xbp1 Mrna ◽  
Transcription Factor Yy1

As a multifunctional transcription factor, YY1 regulates the expression of many genes essential for early embryonic development. RTCB is an RNA ligase that plays a role in tRNA maturation and Xbp1 mRNA splicing. YY1 can bind in vitro to the response element in the proximal promoter of Rtcb and regulate Rtcb promoter activity. However, the in vivo regulation and whether these two genes are involved in the mother-fetal dialogue during early pregnancy remain unclear. In this study, we validated that YY1 bound in vivo to the proximal promoter of Rtcb in mouse uterus of early pregnancy. Moreover, via building a variety of animal models, our study suggested that both YY1 and RTCB might play a role in mouse uterus decidualization and embryo implantation during early pregnancy.

MouseDach1 andDach2 are redundantly required for Müllerian duct development

genesis ◽  
2008 ◽  
Vol 46 (4) ◽  
pp. 205-213 ◽  
Author(s):  
Richard J. Davis ◽  
Mark Harding ◽  
Yalda Moayedi ◽  
Graeme Mardon
Keyword(s):  
Mullerian Duct ◽  
Müllerian Duct ◽  
Duct Development

scholarly journals Studies on sex-organ development. Oestrogenic effect on ornithine decarboxylase activity in the differentiating Müllerian ducts and other organs of the chick embryo

1978 ◽  
Vol 176 (1) ◽  
pp. 143-149 ◽  
Author(s):  
C S Teng ◽  
C T Teng
Keyword(s):  
Enzyme Activity ◽  
Ornithine Decarboxylase ◽  
Decarboxylase Activity ◽  
Mullerian Duct ◽  
Stages Of Development ◽  
Müllerian Duct ◽  
Mullerian Ducts ◽  
The Right ◽  
The Brain

The activity of ornithine decarboxylase in the differentiating left and right Müllerian ducts was assayed and compared with that in other embryonic organs, i.e. the liver and the brain throughout the stages of development. In general the enzyme activity was high in the early stages and decreased extensively in the late stages of development. Specifically, in the left and righ Müllerian ducts, the enzyme activity was high from day 8 to day 9 of incubation. In the right duct the enzyme activity started to decline on day 9 and then continuously decreased to an almost undetectable value on day 18 of incubation. In the left duct the enzyme activity also decreased slightly from day 9 to day 12; however, it increased from day 13 to day 15 and finally decreased to a constant value from day 18 until hatching. The alteration in enzyme activity in the Müllerian duct as assayed in vitro during development is not due to the effect of the size of the endogenous ornithine pool. When the enzyme activity was subjected to oestrogen stimulation, an increase of 5–10-fold for the left duct and of 5–3-fold for the right duct was observed during the course of development. No such stimulation was observed with the treatment of progesterone. Testosterone consistently caused a 25–30% inhibition of the enzyme activity in the Müllerian duct. Oestrogen slightly stimulated the enzyme activity in the developing liver but inhibited that of the brain. The concentration of the three polyamines measured in the Müllerian duct corresponds to the activity of the enzyme determined.

scholarly journals Study on sex-organ development. Oestrogen-receptor translocation in the developing chick Müllerian duct

1976 ◽  
Vol 154 (1) ◽  
pp. 1-9 ◽  
Author(s):  
C S Teng ◽  
C T Teng
Keyword(s):  
Binding Sites ◽  
Developmental Stages ◽  
Dissociation Constants ◽  
Duct Cell ◽  
Mullerian Duct ◽  
Embryonic Chick ◽  
Müllerian Duct ◽  
Initial Content

After oestradiol administration in vivo, 87-95% of the initial concentration of oestradiol receptor in the cytoplasm of the embryonic-chick Müllerian-duct cell was translocated into the nucleus. The process of translocation depends on the amount of oestardiol administered in vivo. At 6 h after oestradiol administration in vivo, about 30% replenishment of the initial content of the cytosol receptor was observed in the cytoplasm. The Müllerian-duct nuclei, after exposure to non-radioactive oestradiol, exhibit saturable exchange with [3H]oestradiol in vitro. The exchange of oestradiol is temperature- and time-dependent. The optimal temperature and time for exchange are 37-41 degrees C and 2h respectively. The [3H]oestradiol-receptor complex extracted from the exchanged nuclei is present in 5-6S form, and its isoelectric point is 6.8. The number of nuclear oestradiol-binding sites of the developing Müllerian duct are 1.66, 2.22, 2.63, and 2.50 pmol/mg of DNA respectively for embryos of 10, 12, 15 and 18 days. The dissociation constants of the nuclear oestradiol receptor of the four observed developmental stages range from 3.0 to 3.1 nM.

Müllerian Duct Development

2017 ◽  
pp. 90-101
Author(s):  
Maribel Acién ◽  
Pedro Acién
Keyword(s):  
Mullerian Duct ◽  
Müllerian Duct ◽  
Duct Development

scholarly journals Endometrial pyruvate kinase M2 is essential for decidualization during early pregnancy

2020 ◽  
Vol 245 (3) ◽  
pp. 357-368 ◽  
Author(s):  
Yan Su ◽  
Sujuan Guo ◽  
Chunyan Liu ◽  
Na Li ◽  
Shuang Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Pyruvate Kinase ◽  
Early Pregnancy ◽  
Stromal Cells ◽  
Embryo Implantation ◽  
Pyruvate Kinase M2 ◽  
Ishikawa Cells ◽  
Implantation Sites

Embryo implantation is essential for normal pregnancy. Decidualization is known to facilitate embryo implantation and maintain pregnancy. Uterine stromal cells undergo transformation into decidual cells after embryo attachment to the endometrium. Pyruvate kinase M2 (PKM2) is a rate limiting enzyme in the glycolysis process which catalyzes phosphoenolpyruvic acid into pyruvate. However, little is known regarding the role of PKM2 during endometrial decidualization. In this study, PKM2 was found to be mainly located in the uterine glandular epithelium and luminal epithelium on day 1 and day 4 of pregnancy and strongly expressed in the decidual zone after embryo implantation. PKM2 was dramatically increased with the onset of decidualization. Upon further exploration, PKM2 was found to be more highly expressed at the implantation sites than at the inter-implantation sites on days 5 to 7 of pregnancy. PKM2 expression was also significantly increased after artificial decidualization both in vivo and in vitro. After PKM2 expression was knocked down by siRNA, the number of embryo implantation sites in mice on day 7 of pregnancy was significantly reduced, and the decidualization markers BMP2 and Hoxa10 were also obviously downregulated in vivo and in vitro. Downregulated PKM2 could also compromise cell proliferation in primary endometrial stromal cells and in Ishikawa cells. The migration rate of Ishikawa cells was also obviously suppressed by si-PKM2 according to the wound healing assay. In conclusion, PKM2 might play an important role in decidualization during early pregnancy, and cell proliferation might be one pathway for PKM2 regulated decidualization.

Molecular mechanisms of hormone-mediated Mullerian duct regression: involvement of beta-catenin

Development ◽  
2000 ◽  
Vol 127 (15) ◽  
pp. 3349-3360 ◽  
Author(s):  
S. Allard ◽  
P. Adin ◽  
L. Gouedard ◽  
N. di Clemente ◽  
N. Josso ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Male Rat ◽  
Beta Catenin ◽  
Mullerian Duct ◽  
Hormone Action ◽  
Male Embryo ◽  
Müllerian Duct ◽  
Enhancer Factor

Regression of the Mullerian duct in the male embryo is one unequivocal effect of anti-Mullerian hormone, a glycoprotein secreted by the Sertoli cells of the testis. This hormone induces ductal epithelial regression through a paracrine mechanism originating in periductal mesenchyme. To probe the mechanisms of action of anti-Mullerian hormone, we have studied the sequence of cellular and molecular events involved in duct regression. Studies were performed in male rat embryos and in transgenic mice overexpressing or lacking anti-Mullerian hormone, both in vivo and in vitro. Anti-Mullerian hormone causes regression of the cranial part of the Mullerian duct whereas it continues to grow caudally. Our work shows that this pattern of regression is correlated with a cranial to caudal gradient of anti-Mullerian hormone receptor protein, followed by a wave of apoptosis spreading along the Mullerian duct as its progresses caudally. Apoptosis is also induced by AMH in female Mullerian duct in vitro. Furthermore, apoptotic indexes are increased in Mullerian epithelium of transgenic mice of both sexes overexpressing the human anti-Mullerian hormone gene, exhibiting a positive correlation with serum hormone concentration. Inversely, apoptosis is reduced in male anti-Mullerian hormone-deficient mice. We also show that apoptosis is a decisive but not sufficient process, and that epitheliomesenchymal transformation is an important event of Mullerian regression. The most striking result of this study is that anti-Mullerian hormone action in peri-Mullerian mesenchyme leads in vivo and in vitro to an accumulation of cytoplasmic beta-catenin. The co-localization of beta-catenin with lymphoid enhancer factor 1 in the nucleus of peri-Mullerian mesenchymal cells, demonstrated in primary culture, suggests that overexpressed beta-catenin in association with lymphoid enhancer factor 1 may alter transcription of target genes and may lead to changes in mesenchymal gene expression and cell fate during Mullerian duct regression. To our knowledge, this is the first report that beta-catenin, known for its role in Wnt signaling, may mediate anti-Mullerian hormone action.

Periductal and matrix glycosaminoglycans in rat Mullerian duct development and regression

1982 ◽  
Vol 92 (1) ◽  
pp. 16-26 ◽  
Author(s):  
Akira Hayashi ◽  
Patricia K. Donahoe ◽  
Gerald P. Budzik ◽  
Robert L. Trelstad
Keyword(s):  
Mullerian Duct ◽  
Müllerian Duct ◽  
Duct Development
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