Loss of WT1 Expression in the Endometrium of Infertile PCOS Patients: A Hyperandrogenic Effect?

González, Deyarina; Thackeray, H.; Lewis, Paul D.; Mantani, A.; Brook, N.; Ahuja, KK; Margara, R.; Joels, Lisa; White, John O.; Conlan, R. Steven

doi:10.1210/jc.2011-2366

Cited by 43 publications

(35 citation statements)

References 32 publications

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“…Not much is known about the roles of KRTAP17-1 , RANBP3L , MPP7 , HCP5 and PTPRN2 in endometrial biology. However, CASP8 has been shown to be among the genes dysregulated in women with chronic endometritis and impaired receptivity 19 , and IVF treatment failure 20 , while WT1 is associated with decidualization in rat endometrial stromal cells 21 , and is downregulated during WOI in polycystic ovary syndrome patients 22 . These lines of evidence support their role among the genes modifying the microenvironment within the receptive endometrium.…”

Section: Discussionmentioning

confidence: 99%

DNA methylation changes in endometrium and correlation with gene expression during the transition from pre-receptive to receptive phase

Kukushkina

Modhukur

Suhorutšenko

et al. 2017

Sci Rep

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The inner uterine lining (endometrium) is a unique tissue going through remarkable changes each menstrual cycle. Endometrium has its characteristic DNA methylation profile, although not much is known about the endometrial methylome changes throughout the menstrual cycle. The impact of methylome changes on gene expression and thereby on the function of the tissue, including establishing receptivity to implanting embryo, is also unclear. Therefore, this study used genome-wide technologies to characterize the methylome and the correlation between DNA methylation and gene expression in endometrial biopsies collected from 17 healthy fertile-aged women from pre-receptive and receptive phase within one menstrual cycle. Our study showed that the overall methylome remains relatively stable during this stage of the menstrual cycle, with small-scale changes affecting 5% of the studied CpG sites (22,272 out of studied 437,022 CpGs, FDR < 0.05). Of differentially methylated CpG sites with the largest absolute changes in methylation level, approximately 30% correlated with gene expression measured by RNA sequencing, with negative correlations being more common in 5′ UTR and positive correlations in the gene ‘Body’ region. According to our results, extracellular matrix organization and immune response are the pathways most affected by methylation changes during the transition from pre-receptive to receptive phase.

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Section: Discussionmentioning

confidence: 99%

DNA methylation changes in endometrium and correlation with gene expression during the transition from pre-receptive to receptive phase

Kukushkina

Modhukur

Suhorutšenko

et al. 2017

Sci Rep

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“…82 The window of implantation occurs in the midsecretory phase of the menstrual cycle, which is a state characterized by low androgen levels. 83 Hyperandrogenic states with persistently elevated androgens, such as PCOS and obesity, likely influence these processes.…”

Section: Hyperandrogenismmentioning

confidence: 99%

Obesity and PCOS: The Effect of Metabolic Derangements on Endometrial Receptivity at the Time of Implantation

2015

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Successful embryonic implantation is the result of a receptive endometrium, a functional embryo at the blastocyst stage and a synchronized dialog between maternal and embryonic tissues. Successful implantation requires the endometrium to undergo steroid-dependent change during each menstrual cycle, exhibiting a short period of embryonic receptivity known as the window of implantation. The term ''endometrial receptivity'' was introduced to define the state of the endometrium during the window of implantation. It refers to the ability of the endometrium to undergo changes that will allow the blastocyst to attach, penetrate, and induce localized changes in the endometrial stroma. These changes are metabolically demanding, and glucose metabolism has been proven to be important for the preparation of the endometrium for embryo implantation. Obesity and polycystic ovary syndrome (PCOS) represent 2 common metabolic disorders that are associated with subfertility. The aim of this review is to summarize the effect of obesity and PCOS on endometrial receptivity at the time of implantation. Focus will be on metabolic alterations that regulate decidualization, including glucose metabolism, hyperinsulinemia, and hyperandrogenism.

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“…The window of implantation is a limited time for blastocyst acceptance in the midsecretory phase of the menstrual cycle, and a state characterized by low androgen levels4. In addition, the endometrium in PCOS patients overexpresses androgen receptor and fails to downregulate estrogen receptor α in the window of implantation5.…”

mentioning

confidence: 99%

Impaired receptivity and decidualization in DHEA-induced PCOS mice

Song

et al. 2016

Sci Rep

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Polycystic ovary syndrome (PCOS), a complex endocrine disorder, is a leading cause of female infertility. An obvious reason for infertility in PCOS women is anovulation. However, success rate with high quality embryos selected by assisted reproduction techniques in PCOS patients still remain low with a high rate of early clinical pregnancy loss, suggesting a problem in uterine receptivity. Using a dehydroepiandrosterone-induced mouse model of PCOS, some potential causes of decreased fertility in PCOS patients were explored. In our study, ovulation problem also causes sterility in PCOS mice. After blastocysts from normal mice are transferred into uterine lumen of pseudopregnant PCOS mice, the rate of embryo implantation was reduced. In PCOS mouse uteri, the implantation-related genes are also dysregulated. Additionally, artificial decidualization is severely impaired in PCOS mice. The serum estrogen level is significantly higher in PCOS mice than vehicle control. The high level of estrogen and potentially impaired LIF-STAT3 pathway may lead to embryo implantation failure in PCOS mice. Although there are many studies about effects of PCOS on endometrium, both embryo transfer and artificial decidualization are applied to exclude the effects from ovulation and embryos in our study.

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Loss of WT1 Expression in the Endometrium of Infertile PCOS Patients: A Hyperandrogenic Effect?

Cited by 43 publications

References 32 publications

DNA methylation changes in endometrium and correlation with gene expression during the transition from pre-receptive to receptive phase

DNA methylation changes in endometrium and correlation with gene expression during the transition from pre-receptive to receptive phase

Obesity and PCOS: The Effect of Metabolic Derangements on Endometrial Receptivity at the Time of Implantation

Impaired receptivity and decidualization in DHEA-induced PCOS mice

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