Cofilin and Slingshot Localization in the Epithelium of Uterine Endometrium Changes During the Menstrual Cycle and in Endometriosis

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Cofilin and slingshot localization in uterine epithelium change with the menstrual cycle and are altered in endometriosis, suggesting cytoskeletal dysregulation impacts fertility.

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This paper studied how the actin-dynamics regulators cofilin and slingshot (SSH1) localize within human uterine epithelial cells across menstrual cycle phases, using dual immunohistochemical staining for cofilin and G-actin. It found that in normal animals cofilin colocalized with G-actin at the apical surface during the proliferative phase, but shifted to basolateral localization during the secretory phase, and quantitative image analysis supported these patterns. Using an established baboon model of induced endometriosis, the authors observed a secretory-phase cofilin/SSH1 distribution resembling the normal proliferative-phase pattern, with SSH1 mRNA upregulation and a suggested progesterone resistance-related nuclear steroid receptor signature, while membrane progesterone receptors (mPRα and mPRβ) were unchanged; the study is limited to tissue staining and mRNA/receptor expression rather than direct functional measures of implantation. This paper is centrally about endometriosis — it demonstrates altered cofilin/SSH1-driven cytoskeleton rearrangement in uterine epithelial tissue in a baboon endometriosis model.

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Abstract

Regulation of the actin cytoskeleton is essential for epithelial cell polarity and protein trafficking within human uterine epithelium. The actin-binding protein cofilin is involved in regulation of actin dynamics by promoting actin branching and cytoskeleton reorganization. Dual immunohistochemical staining of cofilin and G-actin (represented by DNAse I staining) revealed cofilin-G-actin colocalization in the apical side of luminal epithelial cells of human uterine endometrium during the proliferative phase of the menstrual cycle. Interestingly, during the secretory phase of the menstrual cycle, cofilin was only present on the basolateral side. To determine whether the disease endometriosis causes a different pattern of actin remodeling, we investigated an established baboon model of induced endometriosis. The cofilin pattern in the secretory phase of baboons with endometriosis was similar to the proliferative phase in normal animals; cofilin was observed in the apical parts of luminal and glandular epithelium. A phosphatase regulating the activity of cofilin, slingshot (SSH1), revealed a similar staining pattern within these tissues. These patterns were confirmed through quantitative image analysis. Quantification of messenger RNA (mRNA) detected upregulated SSH1 and suggested a progesterone resistance-related pattern of nuclear steroid hormone receptors, but no change in membrane progesterone receptors (mPR alpha or mPR beta) was observed in endometriosis. Our data indicate that the severe dyssynchrony during menstrual cycle phases in endometriosis is connected with improper cytoskeleton rearrangements. We suggest that cofilin-mediated actin reorganization in uterine epithelial cells might be important in preparation for blastocyst implantation; dysregulation of this reorganization may lead to decreased fertility in endometriosis.
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Abstract

Regulation of the actin cytoskeleton is essential for epithelial cell polarity and protein trafficking within human uterine epithelium. The actin-binding protein cofilin is involved in regulation of actin dynamics by promoting actin branching and cytoskeleton reorganization. Dual immunohistochemical staining of cofilin and G-actin (represented by DNAse I staining) revealed cofilin-G-actin colocalization in the apical side of luminal epithelial cells of human uterine endometrium during the proliferative phase of the menstrual cycle. Interestingly, during the secretory phase of the menstrual cycle, cofilin was only present on the basolateral side. To determine whether the disease endometriosis causes a different pattern of actin remodeling, we investigated an established baboon model of induced endometriosis. The cofilin pattern in the secretory phase of baboons with endometriosis was similar to the proliferative phase in normal animals; cofilin was observed in the apical parts of luminal and glandular epithelium. A phosphatase regulating the activity of cofilin, slingshot (SSH1), revealed a similar staining pattern within these tissues. These patterns were confirmed through quantitative image analysis. Quantification of messenger RNA (mRNA) detected upregulated SSH1 and suggested a progesterone resistance-related pattern of nuclear steroid hormone receptors, but no change in membrane progesterone receptors (mPR alpha or mPR beta) was observed in endometriosis. Our data indicate that the severe dyssynchrony during menstrual cycle phases in endometriosis is connected with improper cytoskeleton rearrangements. We suggest that cofilin-mediated actin reorganization in uterine epithelial cells might be important in preparation for blastocyst implantation; dysregulation of this reorganization may lead to decreased fertility in endometriosis. Similar content being viewed by others

References

Adissu HA, Asem EK, Lelievre SA. Three-dimensional cell culture to model epithelia in the female reproductive system. Reprod Sci. 2007;14(8 suppl):11–19 Mellman I, Nelson WJ. Coordinated protein sorting, targeting and distribution in polarized cells. Nat Rev Mol Cell Biol. 2008;9(11):833–845 Li R, Gundersen GG. Beyond polymer polarity: how the cytoskeleton builds a polarized cell. Nat Rev Mol Cell Biol. 2008;9(11):860–873 Nishida E, Maekawa S, Muneyuki E, Sakai H. Action of a 19K protein from porcine brain on actin polymerization: a new functional class of actin-binding proteins. J Biochem. 1984;95(2):387–398 Paavilainen VO, Bertling E, Falck S, Lappalainen P. Regulation of cytoskeletal dynamics by actin-monomer-binding proteins. Trends Cell Biol. 2004;14(7):386–394 Bamburg JR. Proteins of the ADF/cofilin family: essential regulators of actin dynamics. Annu Rev Cell Dev Biol. 1999;15:185–230 Huang TY, DerMardirossian C, Bokoch GM. Cofilin phosphatases and regulation of actin dynamics. Curr Opin Cell Biol. 2006;18(1):26–31 Agnew BJ, Minamide LS, Bamburg JR. Reactivation of phosphorylated actin depolymerizing factor and identification of the regulatory site. J Biol Chem. 1995;270(29):17582–17587 Bamburg JR, Bernstein BW. ADF/cofilin. Curr Biol. 2008;18(7):R273–R275 Niwa R, Nagata-Ohashi K, Takeichi M, Mizuno K, Uemura T. Control of actin reorganization by Slingshot, a family of phosphatases that dephosphorylate ADF/cofilin. Cell. 2002;108(2):233–246 Gohla A, Birkenfeld J, Bokoch GM. Chronophin, a novel HAD-type serine protein phosphatase, regulates cofilin-dependent actin dynamics. Nat Cell Biol. 2005;7(1):21–29 Nishida E, Maekawa S, Sakai H. Cofilin, a protein in porcine brain that binds to actin filaments and inhibits their interactions with myosin and tropomyosin. Biochemistry. 1984;23(22):5307–5313 Gohla A, Bokoch GM. 14-3-3 regulates actin dynamics by stabilizing phosphorylated cofilin. Curr Biol. 2002;12(19):1704–1710 Kligys K, Claiborne JN, DeBiase PJ, et al. The slingshot family of phosphatases mediates Rac1 regulation of cofilin phosphorylation, laminin-332 organization, and motility behavior of keratinocytes. J Biol Chem. 2007;282(44):32520–32528 Soosairajah J, Maiti S, Wiggan O, et al. Interplay between components of a novel LIM kinase-slingshot phosphatase complex regulates cofilin. EMBO J. 2005;24(3):473–486 Eskenazi B, Warner ML. Epidemiology of endometriosis. Obstet Gynecol Clin North Am. 1997;24(2):235–258 Gupta S, Goldberg JM, Aziz N, Goldberg E, Krajcir N, Agarwal A. Pathogenic mechanisms in endometriosis-associated infertility. Fertil Steril. 2008;90(2):247–257 de Ziegler D, Borghese B, Chapron C. Endometriosis and infertility: pathophysiology and management. Lancet. 2010;376(9742):730–738 Slater M, Cooper M, Murphy CR. The cytoskeletal proteins alpha-actinin, Ezrin, and talin are De-expressed in endometriosis and endometrioid carcinoma compared with normal uterine epithelium. Appl Immunohistochem Mol Morphol. 2007;15(2):170–174 Ihnatovych I, Livak M, Reed J, de Lanerolle P, Strakova Z. Manipulating actin dynamics affects human in vitro decidualization. Biol Reprod. 2009;81(1):222–230 Murphy CR. Uterine receptivity and the plasma membrane transformation. Cell Res. 2004;14(4):259–267 Fazleabas AT, Brudney A, Chai D, Langoi D, Bulun SE. Steroid receptor and aromatase expression in baboon endometriotic lesions. Fertil Steril. 2003;80(suppl 2):820–827 Fazleabas AT, Brudney A, Gurates B, Chai D, Bulun S. A modified baboon model for endometriosis. Ann N Y Acad Sci. 2002;955:308–317 Rozen S, Skaletsky H. Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol. 2000;132:365–386 Fernandes MS, Pierron V, Michalovich D, et al. Regulated expression of putative membrane progestin receptor homologues in human endometrium and gestational tissues. J Endocrinol. 2005;187(1):89–101 Romero-Sanchez M, Peiper SC, Evans B, et al. Expression profile of heptahelical putative membrane progesterone receptors in epithelial ovarian tumors. Hum Pathol. 2008;39(7):1026–1033 Ishizuka M, Hatori M, Dohi O, et al. Expression profiles of sex steroid receptors in desmoid tumors. Tohoku J Exp Med. 2006;210(3):189–198 Zitao L, Kuokkanen S, Pal L. Steroid hormone receptor profile of premenopausal endometrial polyps. Reprod Sci. 2010;17(4):377–383 Nakamura Y, Suzuki T, Inoue T, et al. Progesterone receptor subtypes in vascular smooth muscle cells of human aorta. Endocr J. 2005;52(2):245–252 Strakova Z, Reed J, Ihnatovych I. Human transcriptional coactivator with PDZ-binding motif (TAZ) is downregulated during decidualization. Biol Reprod. 2010;82(6):1112–1118 Hastings JM, Jackson KS, Mavrogianis PA, Fazleabas AT. The estrogen early response gene FOS is altered in a baboon model of endometriosis. Biol Reprod. 2006;75(2):176–182 Bernstein BW, Bamburg JR. ADF/cofilin: a functional node in cell biology. Trends Cell Biol. 2010;20(4):187–195 Karlsson AB, Maizels ET, Flynn MP, et al. Luteinizing hormone receptor-stimulated progesterone production by preovulatory granulosa cells requires protein kinase a-dependent activation/ dephosphorylation of the actin dynamizing protein cofilin. Mol Endocrinol. 2010;24(9):1765–1781 Xu YL, Wang DB, Liu QF, Chen YH, Yang Z. Silencing of cofilin-1 gene attenuates biological behaviours of stromal cells derived from eutopic endometria of women with endometriosis. Hum Reprod. 2010;25(10):2480–2488 Pollard TD, Borisy GG. Cellular motility driven by assembly and disassembly of actin filaments. Cell. 2003;112(4):453–465 Luxford KA, Murphy CR. Changes in the apical microfilaments of rat uterine epithelial cells in response to estradiol and progesterone. Anat Rec. 1992;233(4):521–526 Luxford KA, Murphy CR. Reorganization of the apical cytoskeleton of uterine epithelial cells during early pregnancy in the rat: a study with myosin subfragment 1. Biol Cell. 1992;74(2):195–202 Luxford KA, Murphy CR. Cytoskeletal control of the apical surface transformation of rat uterine epithelium. Biol Cell. 1993;79(2):111–116 Terry V, Shaw TJ, Shorey CD, Murphy CR. Actin-binding proteins undergo major alterations during the plasma membrane transformation in uterine epithelial cells. Anat Rec. 1996;246(1):71–77 Birkenfeld J, Betz H, Roth D. Identification of cofilin and LIM-domain-containing protein kinase 1 as novel interaction partners of 14-3-3 zeta. Biochem J. 2003;369(pt 1):45–54 Matsuzaki S, Canis M, Vaurs-Barriere C, Boespflug-Tanguy O, Dastugue B, Mage G. DNA microarray analysis of gene expression in eutopic endometrium from patients with deep endometriosis using laser capture microdissection. Fertil Steril. 2005;84(suppl 4):1180–1190 Grewal S, Carver JG, Ridley AJ, Mardon HJ. Implantation of the human embryo requires Rac1-dependent endometrial stromal cell migration. Proc Natl Acad Sci USA. 2008;105(42):16189–16194 Bulun SE. Endometriosis. N Engl J Med. 2009;360(3):268–279 Fazleabas AT. Progesterone resistance in a baboon model of endometriosis. Semin Reprod Med. 2010;28(1):75–80 Lessey BA, Palomino WA, Apparao KB, Young SL, Lininger RA. Estrogen receptor-alpha (ER-alpha) and defects in uterine receptivity in women. Reprod Biol Endocrinol. 2006;4(suppl 1):S9 Zhu Y, Bond J, Thomas P. Identification, classification, and partial characterization of genes in humans and other vertebrates homologous to a fish membrane progestin receptor. Proc Natl Acad Sci USA. 2003;100(5):2237–2242 Zhu Y, Rice CD, Pang Y, Pace M, Thomas P. Cloning, expression, and characterization of a membrane progestin receptor and evidence it is an intermediary in meiotic maturation of fish oocytes. Proc Natl Acad Sci USA. 2003;100(5):2231–2236 Thomas P. Characteristics of membrane progestin receptor alpha (mPRalpha) and progesterone membrane receptor component 1 (PGMRC1) and their roles in mediating rapid progestin actions. Front Neuroendocrinol. 2008;29(2):292–312 Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Morris, K., Ihnatovych, I., Ionetz, E. et al. Cofilin and Slingshot Localization in the Epithelium of Uterine Endometrium Changes During the Menstrual Cycle and in Endometriosis. Reprod. Sci. 18, 1014–1024 (2011). https://doi.org/10.1177/1933719111401663 Published: Issue date: DOI: https://doi.org/10.1177/1933719111401663

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endometriosis

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Actins Cofilin 1 Cytoskeleton Endometriosis Menstrual Cycle Actins Animals Cofilin 1 Cytoskeleton Cytoskeleton Endometriosis Female Immunohistochemistry Menstrual Cycle Papio

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