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      Endometriosis-associated infertility: From pathophysiology to tailored treatment

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          Abstract

          Despite the clinically recognized association between endometriosis and infertility, the mechanisms implicated in endometriosis-associated infertility are not fully understood. Endometriosis is a multifactorial and systemic disease that has pleiotropic direct and indirect effects on reproduction. A complex interaction between endometriosis subtype, pain, inflammation, altered pelvic anatomy, adhesions, disrupted ovarian reserve/function, and compromised endometrial receptivity as well as systemic effects of the disease define endometriosis-associated infertility. The population of infertile women with endometriosis is heterogeneous, and diverse patients’ phenotypes can be observed in the clinical setting, thus making difficult to establish a precise diagnosis and a single mechanism of endometriosis related infertility. Moreover, clinical management of infertility associated with endometriosis can be challenging due to this heterogeneity. Innovative non-invasive diagnostic tools are on the horizon that may allow us to target the specific dysfunctional alteration in the reproduction process. Currently the treatment should be individualized according to the clinical situation and to the suspected level of impairment. Here we review the etiology of endometriosis related infertility as well as current treatment options, including the roles of surgery and assisted reproductive technologies.

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          Most cited references387

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          Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.

          Exosomes are vesicles of endocytic origin released by many cells. These vesicles can mediate communication between cells, facilitating processes such as antigen presentation. Here, we show that exosomes from a mouse and a human mast cell line (MC/9 and HMC-1, respectively), as well as primary bone marrow-derived mouse mast cells, contain RNA. Microarray assessments revealed the presence of mRNA from approximately 1300 genes, many of which are not present in the cytoplasm of the donor cell. In vitro translation proved that the exosome mRNAs were functional. Quality control RNA analysis of total RNA derived from exosomes also revealed presence of small RNAs, including microRNAs. The RNA from mast cell exosomes is transferable to other mouse and human mast cells. After transfer of mouse exosomal RNA to human mast cells, new mouse proteins were found in the recipient cells, indicating that transferred exosomal mRNA can be translated after entering another cell. In summary, we show that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location. We propose that this RNA is called "exosomal shuttle RNA" (esRNA).
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            Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis

            Patisiran, an investigational RNA interference therapeutic agent, specifically inhibits hepatic synthesis of transthyretin.
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              The microRNA spectrum in 12 body fluids.

              MicroRNAs (miRNAs) are small, noncoding RNAs that play an important role in regulating various biological processes through their interaction with cellular messenger RNAs. Extracellular miRNAs in serum, plasma, saliva, and urine have recently been shown to be associated with various pathological conditions including cancer. With the goal of assessing the distribution of miRNAs and demonstrating the potential use of miRNAs as biomarkers, we examined the presence of miRNAs in 12 human body fluids and urine samples from women in different stages of pregnancy or patients with different urothelial cancers. Using quantitative PCR, we conducted a global survey of the miRNA distribution in these fluids. miRNAs were present in all fluids tested and showed distinct compositions in different fluid types. Several of the highly abundant miRNAs in these fluids were common among multiple fluid types, and some of the miRNAs were enriched in specific fluids. We also observed distinct miRNA patterns in the urine samples obtained from individuals with different physiopathological conditions. MicroRNAs are ubiquitous in all the body fluid types tested. Fluid type-specific miRNAs may have functional roles associated with the surrounding tissues. In addition, the changes in miRNA spectra observed in the urine samples from patients with different urothelial conditions demonstrates the potential for using concentrations of specific miRNAs in body fluids as biomarkers for detecting and monitoring various physiopathological conditions.
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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                26 October 2022
                2022
                : 13
                : 1020827
                Affiliations
                [1] Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine , New Haven, CT, United States
                Author notes

                Edited by: Lusine Aghajanova, Stanford Healthcare, United States

                Reviewed by: Michael Strug, Stanford University, United States; Antonio Simone Laganà, University of Palermo, Italy

                *Correspondence: Hugh S. Taylor, hugh.taylor@ 123456yale.edu

                This article was submitted to Reproduction, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2022.1020827
                9643365
                36387918
                b090d105-e162-4841-bf43-a9819e33b084
                Copyright © 2022 Bonavina and Taylor

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 16 August 2022
                : 06 October 2022
                Page count
                Figures: 3, Tables: 0, Equations: 0, References: 388, Pages: 27, Words: 11918
                Categories
                Endocrinology
                Review

                Endocrinology & Diabetes
                endometriosis,infertility,pathogenesis,ovarian reserve,endometrial receptivity, in-vitro fertilization (ivf),stem cell

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