Ulipristal Acetate Antagonizes the Inhibitory Effect of Progesterone on Ciliary Beat Frequency and Upregulates Steroid Receptor Expression Levels in Human Fallopian Tubes

Yuan, Jiangzi; Zhao, Weihong; Yan, Ming-Xing; Zhu, Qian; Qin, Guo-Juan; Qiu, Jun; Zhang, Jian

doi:10.1177/1933719115589409

Cited by 12 publications

(11 citation statements)

References 34 publications

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“…In addition, we have investigated that the number of epithelial cells of the mucosa of the uterine tube (secretory, basal, ciliated) is not the same throughout the length of the uterine tube of both human and white rats. The largest number of cilia in the fimbriae and ampulla gradually decreases in the direction of the uterus, and the secretory cells are the smallest in the fimbriae and ampulla, and most in the uterine part, which is consistent with the literature [2,25]. As for the structure of the subserosa, there are also several thoughts.…”

Section: Discussionsupporting

confidence: 88%

Comparative anatomy of the uterine tube of human and laboratory white rat females

Podolyuk

2018

Rep. of Morph.

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The world literature has accumulated a considerable amount of data to characterize the main components of the female genital system, functional relationships between them, as well as the links between this system and other systems of the organism. The relevance of the study is also due to the fact that in the structure of female infertility 6070% is occupied by a tubo-peritoneal factor. The problems associated with this pathology have been studied for more than half a century. Until now, information about the microanatomy of the fallopian tube of a human and, especially, of the female white laboratory rat is contradictory. The aim of the study was to conduct a comparative analysis of the structural organization of the uterine tube of a human and female laboratory white rat. The article and analyzes the data of research conducted on 10 sexually mature white rats in females of reproductive age. The method of preparation was used, for the study of macroanatomy of the uterine tube of females, and also standard histological methods (cuts of the wall of the fallopian tube in the thickness of 5-7 microns, stained with hematoxylin and eosin). The external structure of the fallopian tube of the female rat and man has some differences. Unlike humans, the fallopian tube of a white laboratory rat has the appearance of a thin and short tubule, spirally twisted into a compact lump. In the fallopian tube of the female white rat, it is advisable to distinguish 2 parts: the funnel and the fallopian part. The uterine part connects to the uterine horn cavity of the uterine opening of the fallopian tube, and the fallopian tube opens into the cavity of the peritoneum to the surface of the ovary by the abdominal opening of the fallopian tube. Around the funnel of the fallopian tube, its mucous membrane is gathered in folds - the fringe of the fallopian tube and the ovarian fringe (in humans - one ovarian fringe), which are attached to the ovary. The diameter of the fallopian tube of the female white rat decreases in the direction from the funnel to the uterine part. In particular, in the area of the funnel, the diameter of the fallopian tube is 0.90±0.10 mm, and the diameter of the fallopian part is 0.70±0.09 mm. The uterine tube of a laboratory white rat, like a human, has a mesentery of the fallopian tube. Both in human and in female white rat, the wall of the fallopian tube consists of three layers: the inner lining is mucous, the middle lining is muscular, the outer lining is serous. It was established that the female uterine tube of a white rat in its macroscopic structure differs from the uterine tube of a person. The microscopic structure of human and the white rat female uterine tube is rather similar and, therefore, may serve as an object of the experimental modeling of certain pathological conditions of the reproductive system.

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Section: Discussionsupporting

confidence: 88%

Comparative anatomy of the uterine tube of human and laboratory white rat females

Podolyuk

2018

Rep. of Morph.

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“…Our results suggest that UPA does not downregulate PR expression in uterine myomas but instead may prevent the turnover required for their appropriate activity, thereby explaining the antagonist action of UPA. This blockage in PR recycling might also account for the accumulation of PRs seen in the presence of SPRMs reported by other investigators [31, 38-40]. …”

Section: Discussionmentioning

confidence: 72%

“…However, in a murine model of myoma xenografts, PR expression was found to be unchanged after mifepristone treatment [31], probably thanks to the conferred protection against proteasomal degradation [37]. UPA treatment even increased PR expression in 2 models of breast cancer xenografts [38, 39], as well as in the Fallopian tubes [40] and normal endometrium [41-43]. Our results suggest that UPA does not downregulate PR expression in uterine myomas but instead may prevent the turnover required for their appropriate activity, thereby explaining the antagonist action of UPA.…”

Section: Discussionmentioning

confidence: 99%

Progesterone Receptor Isoforms, Nuclear Corepressor-1 and Steroid Receptor Coactivator-1 and B-Cell Lymphoma 2 and Akt and Akt Phosphorylation Status in Uterine Myomas after Ulipristal Acetate Treatment: A Systematic Immunohistochemical Evaluation

Courtoy

Donnez

Marbaix

et al. 2017

Gynecol Obstet Invest

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Objective: To investigate whether ulipristal acetate (UPA) treatment modifies the expression of progesterone receptor (PR), its nuclear cofactors steroid receptor coactivator-1 (SRC1) and nuclear corepressor-1 (NCoR1), prosurvival factor B-cell lymphoma 2 (Bcl-2), and Akt in uterine myomas. Patients: Prospective study of 59 women with symptomatic myomas undergoing myomectomy. Forty-two patients were treated preoperatively with UPA; the remaining 17 were not and they served as controls. Method: Tissue microarrays were obtained from surgical specimens and immunohistochemistry was performed. Blinded quantification of expression of PR (PR-A vs. PR-B), coactivator SRC1 and corepressor NCoR1, and prosurvival factor Bcl-2, and Akt and evaluation of Akt phosphorylation levels. Results: Compared with the control group, UPA does not alter PR protein levels or expression patterns in myomas, and the PR-A/PR-B ratio was similar, as well as cytoplasmic or nuclear expression of cofactors SRC1 and NCoR1. Bcl-2 was heterogeneously expressed throughout the samples and no significant modification in expression was evidenced. No significant difference was found in Akt expression and phosphorylation between treated and untreated myomas. Conclusion: This study did not find any significant change in the expression of the studied factors in myomas after UPA exposure. In conclusion, various theories on myomas cells proposed on the basis of in vitro studies are not supported in vivo.

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“…In contrast Yuan et al (2015) showed that UPA does not directly affect CBF or the ultrastructure of the cilia, but it dose-dependently antagonized the progesterone-induced CBF decrease. To prove the hypothesis of a progesterone antagonist action the authors highlighted that: Mifepristone, an antagonist of the PR, inhibits progesterone-induced CBF reduction ( Mahmood et al, 1998 ); UPA has been shown to be a progesterone antagonistic without agonistic activity in most studied published ( Attardi et al, 2002 ; Chabbert-Buffet et al, 2005 ; Xu et al, 2008 ; Communal et al, 2012 ; Ko et al, 2014 ) and finally, their study demonstrates that UPA is able to up-regulate the expression levels of the estrogen receptor (ER) and the PR in the fallopian tubes, while progesterone down regulates them ( Horne et al, 2009 ).…”

Section: Effects On the Fallopian Tubementioning

confidence: 76%

“…Secondly, in studies on UPA effects on the fallopian tube ( Li et al, 2014 ; Yuan et al, 2015 ) is unclear how it affects fertilization and/or transport of the fertilized egg and therefore the embryo implantation.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of Action of Ulipristal Acetate for Emergency Contraception: A Systematic Review

2016

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Ulipristal acetate (UPA) is now recommended as first choice hormonal emergency contraception (EC), due to its higher efficacy and similar safety compared to Levonorgestrel – EC. Even though all trials demonstrated that the first mechanism of action is inhibition of ovulation, some authors still postulate that a post fertilization effect is also possible, raising the alert on medication and fostering the ethical debate. A Medline database search was performed in order to find recent articles related to UPA’s effects on ovulation, on fallopian tube and on endometrium. We also analyzed the effects on sperm function and pregnancy. All studies conclude that UPA is effective in inhibition of ovulation even when administered shortly before LH peak. The effects on fallopian tube are unclear: according to some authors UPA inhibits ciliar beat through an agonistic effect on progesterone receptors, according to others it antagonizes the progesterone-induced ciliar beat decrease. Concerning the action on endometrium and on embryo implantation most of the studies concluded that low dose UPA used for EC has no significant effect on the decrease of endometrial thickness and on embryo’s attachment, but these results are still matter of debate. Finally recent evidence suggests that UPA modulates human sperm functions while it has no effect on established pregnancy. To date the majority of the evidence concurs in excluding a post-fertilization effect of UPA, even though more studies are needed to clarify its mechanism of action.

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Ulipristal Acetate Antagonizes the Inhibitory Effect of Progesterone on Ciliary Beat Frequency and Upregulates Steroid Receptor Expression Levels in Human Fallopian Tubes

Cited by 12 publications

References 34 publications

Comparative anatomy of the uterine tube of human and laboratory white rat females

Comparative anatomy of the uterine tube of human and laboratory white rat females

Progesterone Receptor Isoforms, Nuclear Corepressor-1 and Steroid Receptor Coactivator-1 and B-Cell Lymphoma 2 and Akt and Akt Phosphorylation Status in Uterine Myomas after Ulipristal Acetate Treatment: A Systematic Immunohistochemical Evaluation

Mechanism of Action of Ulipristal Acetate for Emergency Contraception: A Systematic Review

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