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The Multifaceted Role of Autophagy in Endometrium Homeostasis and Disease

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Abstract

Autophagy is a conserved fundamental cellular process with a primary function of catabolizing harmful or surplus cellular contents such as protein aggregates, dysfunctional/long-lived organelles, intracellular pathogens, and storage nutrients. An increasing body of evidence reveals that basal autophagy is essential for maintaining endometrial homeostasis and mediating endometrial-specific functions, including menstrual cycle, embryo implantation, and decidualization. However, perturbed levels of autophagy can lead to severe endometrial pathologies, including endometriosis, endometrial hyperplasia, endometrial cancer, adenomyosis, and leiomyoma. This review highlights the most recent findings on the activity, regulation, and function of autophagy in endometrium physiology and pathology. Understanding the mechanistic roles of autophagy in endometrium homeostasis and disease is key to developing novel therapeutic strategies for endometrium-related infertility and malignancies.

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Abbreviations

ATG:

Autophagy-related gene

BECN1:

Beclin 1

CMA:

Chaperone-mediated autophagy

LC3B-II:

Microtubule-associated proteins 1A/1B light chain 3B

mTORC:

Mechanistic target of rapamycin complex

ULK:

unc-51-like kinase

UVRAG:

UV resistance-associated gene

HESCs:

Human endometrial stromal cells

EC:

Endometrial cancer

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Acknowledgements

We thank Jennifer Brazill, Mandy Chan, and Anne Robinson for assisting with schematic figure preparation in association with InPrint, Washington University, St. Louis, MO. We also thank Anthony Bartley, Scientific Graphic Designer for Fig. 1 preparation, Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO.

Funding

This work was funded, in part, by the National Institutes of Health/National Institute of Child Health and Human Development grants R00HD080742, RO1HD065435 and R01HD102680 to RK and Washington University School of Medicine start-up funds to RK.

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  1. Pooja Popli and Ally J. Sun contributed equally to this work.

Authors and Affiliations

  1. Center for Reproductive Health Sciences, Department of Obstetrics and Gynecology, Washington University School of Medicine, BJC Institute of Health - 10th Floor, RM 10606, 425 S. Euclid Avenue, Campus Box 8064, St. Louis, MO, 63110, USA

    Pooja Popli, Ally J. Sun & Ramakrishna Kommagani

  2. School of Arts and Sciences, Department of Biology, Washington University School of Medicine, St. Louis, MO, 63110, USA

    Ally J. Sun

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  1. Pooja Popli
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PP, AJS, and RK wrote the article. All authors reviewed and approved the final version of the article.

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Correspondence to Ramakrishna Kommagani.

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Popli, P., Sun, A.J. & Kommagani, R. The Multifaceted Role of Autophagy in Endometrium Homeostasis and Disease. Reprod. Sci. 29, 1054–1067 (2022). https://doi.org/10.1007/s43032-021-00587-2

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