Impaired receptivity and decidualization in DHEA-induced PCOS mice

Abstract

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.

Metformin Ameliorates Uterine Defects in a Rat Model of Polycystic Ovary Syndrome

“…A number of molecules in the uterus have been shown to be required for implantation, and aberrations in these molecules cause reproductive failure ( Cha et al, 2012 , Zhang et al, 2013 ). Together with studies showing that endometrial decidualization is impaired in PCOS patients ( Piltonen et al, 2015 ) and that several implantation-related genes (e.g., Lif , Ihh , Sgk1 , Msx1 , Hand2 , and Muc1 ) are dysregulated in the DHEA-treated mouse uterus ( Li et al, 2016a ), we found that metformin fails to correct the abnormal levels of some of the implantation-related genes ( Lif , Pc6 , and Sgk1 ) in the PCOS-like rat uterus. Moreover, PCOS-like rats with implantation failure despite metformin treatment exhibited significant dysregulation of uterine Prl , Maoa , Ednrb , and Hbegf mRNA expression compared with control and PCOS-like rats with implantation.…”

Nucleolar stress regulation of endometrial receptivity in mouse models and human cell lines

“…Immunohistochemistry was performed as previously described 28 . The paraffin sections (5 μm) were deparaffinized in xylene, rehydrated with a graded series of ethanol, and washed in water.…”

Methylglyoxal-Dependent Glycative Stress and Deregulation of SIRT1 Functional Network in the Ovary of PCOS Mice

“…Twenty 4 week-old, body weight 20-21 g, young CD-1 female mice were randomly assigned to two groups (10 for each): mice daily injected (sub cutaneously) with DHEA (6 mg/100 g body weight, 100 µL/mouse in sesame oil with 10% of 95% ethanol, Sigma-Aldrich, St. Louis, CO, USA) for 20 consecutive days (DHEA mice) [20,21]. The vehicle control group was injected with 0.09 mL sesame oil and 0.01 mL 95% ethanol daily for 20 consecutive days (control mice).…”

“…In the present work, we hypothesized that MG-dependent glycative stress participates in ovarian PCOS phenotype and explored whether this condition is associated with deregulation of SIRT1 functional network regulating mitochondrial physiology and cell survival. To this end, we relied on a dehydroepiandrosterone (DHEA)-induced PCOS model developed in CD1 mice [20], known to share many of the salient features with human PCOS patients [21]. The occurrence of PCOS was confirmed by analysing different parameters including follicle population, ovarian fibrosis, dyslipidemia, oestrous cycle, ovulation, oocyte quality and oxidative stress.…”