Abnormal Pathways in Endometriosis in Relation to Progesterone Resistance: A Review

Lode, Lise; Sveen, Magnhild Often; Rudnicki, Martin

doi:10.5301/jeppd.5000302

Cited by 7 publications

(4 citation statements)

References 50 publications

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“…Altered ratios of PR-A and PR-B expressions have been associated with the development of progesterone resistance ( 33 ). In addition, the upregulation of aromatase and increased level of estrogen contribute to the dysregulation of progesterone signaling ( 34 ). The development of progesterone resistance and its effects on the WOI are not clearly understood.…”

Section: Potential Mechanisms Regulating the Optimal Woimentioning

confidence: 99%

Non-Invasive and Mechanism-Based Molecular Assessment of Endometrial Receptivity During the Window of Implantation: Current Concepts and Future Prospective Testing Directions

Sun

Yeh

2022

Front. Reprod. Health

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Suboptimal endometrial receptivity and altered embryo-endometrial crosstalk account for approximately two-thirds of human implantation failures. Current tests of the window of implantation, such as endometrial thickness measurements and the endometrial receptivity assay, do not consistently improve clinical outcomes as measured by live birth rates. Understanding the mechanisms regulating the endometrial receptivity during the window of implantation is a critical step toward developing clinically meaningful tests. In this narrative review, the available literature is evaluated regarding mechanisms that regulate the endometrial receptivity during the window of implantation and the current tests developed. Overall, both animal and human studies point to five possible and interrelated mechanisms regulating the endometrial window of implantation: suitable synchrony between endometrial cells, adequate synchrony between the endometrium and the embryo, standard progesterone signaling and endometrial responses to progesterone, silent genetic variations, and typical morphological characteristics of the endometrial glands. The biological basis of current clinical markers or tests of window of implantation is poor. Future studies to elucidate the mechanisms shaping the window of implantation and to investigate the potential markers based on these mechanisms are required. In addition, molecular testing of the endometrium at single-cell resolution should be an initial step toward developing clinically meaningful tests for the optimal window of implantation. As understanding of the optimal window of implantation continues to evolve, one can envision the future development of non-invasive, mechanism-based testing of the window of implantation.

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Section: Potential Mechanisms Regulating the Optimal Woimentioning

confidence: 99%

Non-Invasive and Mechanism-Based Molecular Assessment of Endometrial Receptivity During the Window of Implantation: Current Concepts and Future Prospective Testing Directions

Sun

Yeh

2022

Front. Reprod. Health

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“…How is PGR expression and response in target cells from females with endometriosis affected by other linked molecular mechanisms? 11,21,26,68,69 Several such unmet questions point to the fact that there is an urgent need for a better understanding of the nuanced characteristics of progesterone resistance in ectopic and eutopic tissue in endometriosis, to innovate better management and treatment of progesterone resistance in the future.…”

Section: Mechanisms Of Progesterone Resistance In Endometriosismentioning

confidence: 99%

Progesterone Resistance in Endometriosis

et al. 2022

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Endometriosis is characterised by the presence of endometrium-like tissue on the pelvis and other organs. Progesterone resistance due to suppressed progesterone receptor (PGR) expression and action is a general feature of endometriosis and is a cause of endometriosis-associated chronic pelvic pain, infertility, inflammatory disorders, and cancer. It appears that progesterone receptor polymorphisms may not be associated with the susceptibility to endometriosis. On the other hand, PGR expression and activity in target cells is significantly dysregulated in both eutopic and ectopic tissues compared with control endometrium. However, the underlying epigenetic mechanisms for PGR suppression in the eutopic tissue are different from ectopic tissue. The aim of this paper was to present an overview of different aspects of progesterone resistance and its application in endometriosis. Finally, this article also presents a few important, unmet questions related to the failure of progesterone treatment in alleviating clinical conditions in endometriosis.

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“…We would require data spanning multiple months in order to build a comprehensive hormone profile with any hope of revealing important reproductive features, especially in the absence of clearly identifiable ovulatory states. Still more confounding are conditions such as endometriosis, which lack a clear etiology, yet are linked to circulating hormone levels [4].…”

Section: Introductionmentioning

confidence: 99%

Reduced model for female endocrine dynamics: Validation and functional variations

Graham¹,

Elhadad²,

Albers³

2020

Preprint

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A normally functioning menstrual cycle requires significant crosstalk between hormones originating in ovarian and brain tissues. Reproductive hormone dysregulation may cause abnormal function and sometimes infertility. The inherent complexity in this endocrine system is a challenge to identifying mechanisms of cycle disruption, particularly given the large number of unknown parameters in existing mathematical models. We develop a new endocrine model to limit model complexity and use simulated distributions of unknown parameters for model analysis. By employing a comprehensive model evaluation, we identify a collection of mechanisms that differentiate normal and abnormal phenotypes. We also discover an intermediate phenotype-displaying relatively normal hormone levels and cycle dynamics-that is grouped statistically with the irregular phenotype. Results provide insight into how clinical symptoms associated with ovulatory disruption may not be detected through hormone measurements alone.

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Abnormal Pathways in Endometriosis in Relation to Progesterone Resistance: A Review

Cited by 7 publications

References 50 publications

Non-Invasive and Mechanism-Based Molecular Assessment of Endometrial Receptivity During the Window of Implantation: Current Concepts and Future Prospective Testing Directions

Non-Invasive and Mechanism-Based Molecular Assessment of Endometrial Receptivity During the Window of Implantation: Current Concepts and Future Prospective Testing Directions

Progesterone Resistance in Endometriosis

Reduced model for female endocrine dynamics: Validation and functional variations

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