Histomorphometric Analysis and Markers of Endometrial Receptivity Embryonic Implantation in Women With Polycystic Ovary Syndrome During the Treatment With Progesterone

Lopes, Ione Maria Ribeiro Soares; Maganhin, Carla Cristina; Oliveira‐Filho, Ricardo Martins; Simões, Ricardo Santos; Simões, Manuel J.; Iwata, Margareth Chiharu; Baracat, Edmund Chada; Soares, José Maria

doi:10.1177/1933719113519169

Cited by 34 publications

(27 citation statements)

References 36 publications

(64 reference statements)

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“…Although progesterone (P4)-based oral contraceptive therapy is often efficacious 7,8 , perturbations in endometrial P4 signaling that result from attenuated responsiveness and resistance to P4 are common in the endometrium of a PCOS patient 9,10 . P4 resistance is a condition in which tissues and cells do not respond appropriately to P4 11 , and this is evidenced by endometriosis and endometrial hyperplasia that may progress to endometrial carcinoma despite supplementation with P4 or its analogs 12,13 .…”

mentioning

confidence: 99%

Uterine progesterone signaling is a target for metformin therapy in PCOS-like rats

Zhang

Feng

et al. 2017

Preprint

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Impaired progesterone (P4) signaling is linked to endometrial dysfunction and infertility in women with polycystic ovary syndrome (PCOS). Here we report for the first time that elevated expression of progesterone receptor (PGR) isoforms A and B parallels increased estrogen receptor (ER) expression in PCOS-like rat uteri. The aberrant PGR-targeted gene expression in PCOS-like rats before and after implantation overlaps with dysregulated expression of Fkbp52 and Ncoa2, two genes that contribute to the development of uterine P4 resistance. In vivo and in vitro studies of the effects of metformin on the regulation of the uterine P4 signaling pathway under PCOS conditions showed that metformin directly inhibits the expression of PGR and ER along with the regulation of several genes that are targeted dependently or independently of PGR-mediated uterine implantation. Functionally, metformin treatment corrected the abnormal expression of cell-specific PGR and ER and some PGR-target genes in PCOS-like rats with implantation. Additionally, we documented how metformin contributes to the regulation of the PGR-associated MAPK/ERK/p38 signaling pathway in the PCOS-like rat uterus. Our data provide novel insights into how metformin therapy regulates uterine P4 signaling molecules under PCOS conditions.

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mentioning

confidence: 99%

Uterine progesterone signaling is a target for metformin therapy in PCOS-like rats

Zhang

Feng

et al. 2017

Preprint

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“…Furthermore, data on stromal (non-epithelial) structures in the endometrium of women with PCOS are lacking [3, 10, 24, 25]. Therefore, our pilot study has contributed to the scientific literature with the following two findings: a) demonstrating the presence of SLRPs in the endometrium of women with PCOS; and b) demonstrating that the SLRP content in these women appears to be abnormal, specifically appearing to be enhanced relative to normals.…”

Section: Discussionmentioning

confidence: 87%

“…In women with PCOS there is a deficiency in cyclic progesterone production due to chronic anovulation and a relative increase in other substances, such as insulin, cytokines, and growth factors, which results in an imbalance in endometrial hemostasis in these patients, possibly leading to abnormal uterine bleeding, infertility, and an increased risk of developing endometrial hyperplasia [3, 21–25]. The specific receptors for insulin and Insulin Growth Factors (IGFs) as well as high-affinity IGF-binding proteins (IGFBPs) have been detected in endometrial tissues [26].…”

Section: Discussionmentioning

confidence: 99%

Small leucine-rich proteoglycans (SLRPs) in the endometrium of polycystic ovary syndrome women: a pilot study

et al. 2017

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BackgroundSmall leucine-rich proteoglycans (SLRPs) play an important role in tissue homeostasis and cell proliferation since these proteoglycans sequester multiple growth factors. However, the content of SLRPs in the endometrium of polycystic ovary syndrome (PCOS) women is unknown. Our purpose was to test the hypothesis that excessive endometrial proliferation in PCOS may be partly related to abnormalities in SLRPs.MethodsIn a cross section study a total of 20 endometrial samples were collected from 10 patients with PCOS and 10 ovulatory women during their proliferative (pre-ovulatory) phase. The study subjects were matched for age, body mass index and race. The age range was 20 to 35 years. All volunteers were evaluated in reproductive endocrinology clinic, Gynecology Division, Clinics Hospital, University of São Paulo Medical School Profile and concentration of small leucine-rich proteoglycans (decorin, lumican, fibromodulin and biglycan) were determined by immunohistochemical testing and Western blotting.ResultsDecorin and lumican demonstrated higher immunoreactivity and relative expression in the endometrium of women with PCOS compared to that of women with regular menstrual cycles.ConclusionOur data suggests that the endometrium of PCOS women demonstrate a greater content of SLRP than controls; decorin and lumican, in particular, were found in higher concentrations in the endometrium of PCOS women during the proliferative phase. These differences may, in part, explain the excess of endometrial proliferation frequently observed in PCOS. Further studies are warranted.

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“…In vitro findings, as well as endometrial biopsies obtained from women with PCOS, show that testosterone decreases HOXA10-mRNA, leading to the conclusion that diminished uterine HOXA10 expression may contribute to the diminished reproduction potential of women with PCOS. A review of endometrial aspects of the "window of implantation" in women with PCOS, focusing mainly on adhesion molecules, suggested that endometrial receptivity seems to be the major limiting factor for the establishment of pregnancy [4]. Savaris et al [20] compared gene expression between endometrial samples of normal fertile controls and women with PCOS, concluding that existing differences in gene expression provide evidence of progesterone resistance in mid-secretory PCOS endometrium, independent of clomiphene citrate.…”

Section: Accepted Manuscriptmentioning

confidence: 98%

“…Indeed, there is evidence that infertility in women with PCOS cannot be attributed only to anovulation, but also to endometrial dysfunction. A recent endometrial biopsy study by Lopes et al [4] showed that conventional doses of progesterone may not be enough to correct PCOS-associated changes in the endometrial histomorphology and the receptivity markers. It is a fact that despite the ability to correct ovulatory disorders in PCOS, pregnancy rates remain paradoxically low, and spontaneous pregnancy loss rates are high [5].…”

Section: Introductionmentioning

confidence: 97%

Menstrual preconditioning for the prevention of major obstetrical syndromes in polycystic ovary syndrome

Brosens

Benagiano

2015

American Journal of Obstetrics and Gynecology

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The presence of multiple ovarian cysts, anovulation, and endometrial progesterone resistance in the neonate seems remarkably similar to ovarian and endometrial features of the polycystic ovary syndrome (PCOS) of adolescent and adult women. In fact, in the absence of cyclic menstruations after menarche, the neonatal progesterone resistance is likely to persist and adversely affect young women with PCOS at the time of pregnancy after induction of ovulation, because any persisting defect in progesterone response can interfere with the process of decidualization and trophoblast invasion. The primigravid woman with PCOS therefore is likely to be at risk of defective deep placentation as manifested by the increased risk of major obstetric syndromes. A recent, large epidemiologic study has demonstrated that the risk of preeclampsia and preterm delivery is elevated in the 13- to 15-year old group, although it does not persist in the 16- to 17-year old group. It is proposed therefore that induction of ovulation in the infertile nulligravid woman with PCOS should be preceded by a period of progesterone withdrawal bleedings to achieve full endometrial progesterone response by the time of pregnancy. The cyclic administration of clomiphene citrate for a period to be determined by vascular response may be an appropriate tool to reduce the risk of major obstetric syndromes by menstrual preconditioning.

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Histomorphometric Analysis and Markers of Endometrial Receptivity Embryonic Implantation in Women With Polycystic Ovary Syndrome During the Treatment With Progesterone

Cited by 34 publications

References 36 publications

Uterine progesterone signaling is a target for metformin therapy in PCOS-like rats

Uterine progesterone signaling is a target for metformin therapy in PCOS-like rats

Small leucine-rich proteoglycans (SLRPs) in the endometrium of polycystic ovary syndrome women: a pilot study

Menstrual preconditioning for the prevention of major obstetrical syndromes in polycystic ovary syndrome

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