{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:08:50Z","timestamp":1790896130029,"version":"4.1.0"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T00:00:00Z","timestamp":1597276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T00:00:00Z","timestamp":1597276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Local renin-angiotensin system (RAS) in female reproductive system is involved in many physiological and pathological processes, such as follicular development, ovarian angiogenesis, ovarian, and endometrial cancer progress. However, studies on the functional relevance of RAS in human endometrium are limited, especially for renin-angiotensin-aldosterone system (RAAS). In this study, we defined the location of RAS components in human endometrium. We found that angiotensin II type-1 receptor (AT<jats:sub>1<\/jats:sub>R) and aldosterone synthase (CYP11B2), major components of RAAS, are specifically expressed in endometrial gland during mid-secretory phase. Aldosterone receptor, mineralocorticoid receptor (MR), is elevated in stroma in mid-secretory endometrium. In vitro, MR is also activated by aldosterone during decidualization. Activated MR initiates LKB1 expression, followed by phosphorylating of AMPK that stimulates PDK4 expression. The impact of PDK4 on decidualization is independent on PDHE1\u03b1 inactivation. Based on co-immunoprecipitation, PDK4 interacts with p-CREB to prevent its ubiquitination for facilitating decidualization via FOXO1. Restrain of MR activation interrupts LKB1\/p-AMPK\/PDK4\/p-CREB\/FOXO1 pathway induced by aldosterone, indicating that aldosterone action on decidualization is mainly dependent on MR stimulation. Aldosterone biosynthesized in endometrial gland during mid-secretory phase promotes decidualization via activating MR\/LKB1\/p-AMPK\/PDK4\/p-CREB\/FOXO1 signaling pathway. This study provides the valuable information for understanding the underlying mechanism during decidualization.<\/jats:p>","DOI":"10.1038\/s41419-020-02844-9","type":"journal-article","created":{"date-parts":[[2020,8,21]],"date-time":"2020-08-21T12:02:54Z","timestamp":1598011374000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Aldosterone from endometrial glands is benefit for human decidualization"],"prefix":"10.1038","volume":"11","author":[{"given":"Shu-Yun","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Ping","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Jie","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue-Fang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-Shan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Yuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai-Xia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7915-4568","authenticated-orcid":false,"given":"Song","family":"Quan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeng-Ming","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,13]]},"reference":[{"key":"2844_CR1","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1210\/er.2014-1045","volume":"35","author":"B Gellersen","year":"2014","unstructured":"Gellersen, B. & Brosens, J. J. Cyclic decidualization of the human endometrium in reproductive health and failure. Endocr. Rev. 35, 851\u2013905 (2014).","journal-title":"Endocr. Rev."},{"key":"2844_CR2","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1038\/nm.3012","volume":"18","author":"J Cha","year":"2012","unstructured":"Cha, J., Sun, X. & Dey, S. K. Mechanisms of implantation: strategies for successful pregnancy. Nat. Med. 18, 1754\u20131767 (2012).","journal-title":"Nat. Med."},{"key":"2844_CR3","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1056\/NEJM198807283190401","volume":"319","author":"AJ Wilcox","year":"1988","unstructured":"Wilcox, A. J. et al. Incidence of early loss of pregnancy. N. Engl. J. Med. 319, 189\u2013194 (1988).","journal-title":"N. Engl. J. Med."},{"key":"2844_CR4","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/S0015-0282(16)58144-8","volume":"65","author":"MJ Zinaman","year":"1996","unstructured":"Zinaman, M. J., Clegg, E. D., Brown, C. C., O\u2019Connor, J. & Selevan, S. G. Estimates of human fertility and pregnancy loss. Fertil. Steril. 65, 503\u2013509 (1996).","journal-title":"Fertil. Steril."},{"key":"2844_CR5","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1387\/ijdb.130344ts","volume":"58","author":"J Filant","year":"2014","unstructured":"Filant, J. & Spencer, T. E. Uterine glands: biological roles in conceptus implantation, uterine receptivity and decidualization. Int. J. Dev. Biol. 58, 107\u2013116 (2014).","journal-title":"Int. J. Dev. Biol."},{"key":"2844_CR6","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-018-04848-8","volume":"9","author":"AM Kelleher","year":"2018","unstructured":"Kelleher, A. M., Milano-Foster, J., Behura, S. K. & Spencer, T. E. Uterine glands coordinate on-time embryo implantation and impact endometrial decidualization for pregnancy success. Nat. Commun. 9, 2435 (2018).","journal-title":"Nat. Commun."},{"key":"2844_CR7","doi-asserted-by":"crossref","first-page":"E8468","DOI":"10.1073\/pnas.1706546114","volume":"114","author":"T Garrido-Gomez","year":"2017","unstructured":"Garrido-Gomez, T. et al. Defective decidualization during and after severe preeclampsia reveals a possible maternal contribution to the etiology. Proc. Nat. Acad. Sci. USA 114, E8468\u2013E8477 (2017).","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"2844_CR8","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1055\/s-2007-991042","volume":"25","author":"B Gellersen","year":"2007","unstructured":"Gellersen, B., Brosens, I. A. & Brosens, J. J. Decidualization of the human endometrium: mechanisms, functions, and clinical perspectives. Semin. Reprod. Med. 25, 445\u2013453 (2007).","journal-title":"Semin. Reprod. Med."},{"key":"2844_CR9","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1152\/physrev.00036.2005","volume":"86","author":"M Paul","year":"2006","unstructured":"Paul, M., Poyan Mehr, A. & Kreutz, R. Physiology of local renin-angiotensin systems. Physiol. Rev. 86, 747\u2013803 (2006).","journal-title":"Physiol. Rev."},{"key":"2844_CR10","doi-asserted-by":"crossref","first-page":"3054","DOI":"10.2174\/1381612811319170012","volume":"19","author":"Y Uehara","year":"2013","unstructured":"Uehara, Y., Miura, S., Yahiro, E. & Saku, K. Non-ACE pathway-induced angiotensin II production. Curr. Pharm. Des. 19, 3054\u20133059 (2013).","journal-title":"Curr. Pharm. Des."},{"key":"2844_CR11","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1152\/physrev.00038.2017","volume":"98","author":"SJ Forrester","year":"2018","unstructured":"Forrester, S. J. et al. Angiotensin II signal transduction: an update on mechanisms of physiology and pathophysiology. Physiol. Rev. 98, 1627\u20131738 (2018).","journal-title":"Physiol. Rev."},{"key":"2844_CR12","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.atherosclerosis.2017.05.029","volume":"263","author":"A Nehme","year":"2017","unstructured":"Nehme, A. & Zibara, K. Cellular distribution and interaction between extended renin-angiotensin-aldosterone system pathways in atheroma. Atherosclerosis 263, 334\u2013342 (2017).","journal-title":"Atherosclerosis"},{"key":"2844_CR13","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1111\/j.1445-5994.1995.tb02884.x","volume":"25","author":"PJ Fuller","year":"1995","unstructured":"Fuller, P. J. Aldosterone and its mechanism of action: more questions than answers. Aust. N. Z. J. Med. 25, 800\u2013807 (1995).","journal-title":"Aust. N. Z. J. Med."},{"key":"2844_CR14","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1046\/j.1523-1755.2000.00975.x","volume":"57","author":"JW Funder","year":"2000","unstructured":"Funder, J. W. Aldosterone and mineralocorticoid receptors: orphan questions. Kidney Int. 57, 1358\u20131363 (2000).","journal-title":"Kidney Int."},{"key":"2844_CR15","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/S1043-2760(00)00356-8","volume":"12","author":"RC Wilson","year":"2001","unstructured":"Wilson, R. C., Nimkarn, S. & New, M. I. Apparent mineralocorticoid excess. Trends Endocrinol. Metab. 12, 104\u2013111 (2001).","journal-title":"Trends Endocrinol. Metab."},{"key":"2844_CR16","first-page":"135","volume":"18","author":"PC White","year":"1997","unstructured":"White, P. C., Mune, T. & Agarwal, A. K. 11 beta-Hydroxysteroid dehydrogenase and the syndrome of apparent mineralocorticoid excess. Endocr. Rev. 18, 135\u2013156 (1997).","journal-title":"Endocr. Rev."},{"key":"2844_CR17","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1172\/JCI114121","volume":"83","author":"KJ Shaw","year":"1989","unstructured":"Shaw, K. J. et al. Human decidua is a major source of renin. J. Clin. Invest. 83, 2085\u20132092 (1989).","journal-title":"J. Clin. Invest."},{"key":"2844_CR18","doi-asserted-by":"crossref","first-page":"2804","DOI":"10.1093\/humrep\/12.12.2804","volume":"12","author":"XF Li","year":"1997","unstructured":"Li, X. F. & Ahmed, A. Compartmentalization and cyclic variation of immunoreactivity of renin and angiotensin converting enzyme in human endometrium throughout the menstrual cycle. Hum. Reprod. 12, 2804\u20132809 (1997).","journal-title":"Hum. Reprod."},{"key":"2844_CR19","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1172\/JCI118131","volume":"96","author":"A Ahmed","year":"1995","unstructured":"Ahmed, A. et al. Localization of the angiotensin II and its receptor subtype expression in human endometrium and identification of a novel high-affinity angiotensin II binding site. J. Clin. Invest. 96, 848\u2013857 (1995).","journal-title":"J. Clin. Invest."},{"key":"2844_CR20","doi-asserted-by":"crossref","first-page":"E855","DOI":"10.1152\/ajpendo.00526.2002","volume":"284","author":"MC Sugden","year":"2003","unstructured":"Sugden, M. C. & Holness, M. J. Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs. Am. J. Physiol. Endocrinol. Metab. 284, E855\u2013862 (2003).","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"2844_CR21","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1101\/gad.1661708","volume":"22","author":"L Lai","year":"2008","unstructured":"Lai, L. et al. Transcriptional coactivators PGC-1alpha and PGC-lbeta control overlapping programs required for perinatal maturation of the heart. Genes Dev. 22, 1948\u20131961 (2008).","journal-title":"Genes Dev."},{"key":"2844_CR22","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1080\/13813450600935263","volume":"112","author":"MC Sugden","year":"2006","unstructured":"Sugden, M. C. & Holness, M. J. Mechanisms underlying regulation of the expression and activities of the mammalian pyruvate dehydrogenase kinases. Arch. Physiol. Biochem. 112, 139\u2013149 (2006).","journal-title":"Arch. Physiol. Biochem."},{"key":"2844_CR23","doi-asserted-by":"crossref","first-page":"39897","DOI":"10.1074\/jbc.M608657200","volume":"281","author":"Y Zhang","year":"2006","unstructured":"Zhang, Y. et al. Estrogen-related receptors stimulate pyruvate dehydrogenase kinase isoform 4 gene expression. J. Biol. Chem. 281, 39897\u201339906 (2006).","journal-title":"J. Biol. Chem."},{"key":"2844_CR24","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/nature12154","volume":"498","author":"J Kaplon","year":"2013","unstructured":"Kaplon, J. et al. A key role for mitochondrial gatekeeper pyruvate dehydrogenase in oncogene-induced senescence. Nature 498, 109\u2013112 (2013).","journal-title":"Nature"},{"key":"2844_CR25","doi-asserted-by":"crossref","first-page":"21280","DOI":"10.1074\/jbc.M115.656629","volume":"290","author":"RJ Zuo","year":"2015","unstructured":"Zuo, R. J. et al. Warburg-like glycolysis and lactate shuttle in mouse decidua during early pregnancy. J. Biol. Chem. 290, 21280\u201321291 (2015).","journal-title":"J. Biol. Chem."},{"key":"2844_CR26","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1003900","volume":"9","author":"R Kommagani","year":"2013","unstructured":"Kommagani, R. et al. Acceleration of the glycolytic flux by steroid receptor coactivator-2 is essential for endometrial decidualization. PLoS Genet 9, e1003900 (2013).","journal-title":"PLoS Genet"},{"key":"2844_CR27","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0940-9602(11)80416-4","volume":"176","author":"HW Denker","year":"1994","unstructured":"Denker, H. W. Endometrial receptivity: cell biological aspects of an unusual epithelium. A review. Ann. Anat. 176, 53\u201360 (1994).","journal-title":"Ann. Anat."},{"key":"2844_CR28","doi-asserted-by":"crossref","first-page":"e93","DOI":"10.1016\/j.fertnstert.2019.08.079","volume":"112","author":"RW Noyes","year":"2019","unstructured":"Noyes, R. W., Hertig, A. T. & Rock, J. Reprint of: dating the endometrial biopsy. Fertil. Steril. 112, e93\u2013e115 (2019).","journal-title":"Fertil. Steril."},{"key":"2844_CR29","doi-asserted-by":"crossref","unstructured":"Brighton, P. J. et al. Clearance of senescent decidual cells by uterine natural killer cells in cycling human endometrium. Elife. 6, e31274 (2017).","DOI":"10.7554\/eLife.31274"},{"key":"2844_CR30","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1002\/rmb2.12226","volume":"17","author":"M Kimura","year":"2018","unstructured":"Kimura, M., Kajihara, T., Mizuno, Y., Sato, T. & Ishihara, O. Loss of high-mobility group N5 contributes to the promotion of human endometrial stromal cell decidualization. Reprod. Med. Biol. 17, 493\u2013499 (2018).","journal-title":"Reprod. Med. Biol."},{"key":"2844_CR31","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1002\/1873-3468.12645","volume":"591","author":"SY Li","year":"2017","unstructured":"Li, S. Y. et al. Molecular characterization of lysyl oxidase-mediated extracellular matrix remodeling during mouse decidualization. FEBS Lett. 591, 1394\u20131407 (2017).","journal-title":"FEBS Lett."},{"key":"2844_CR32","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak, K. J. & Schmittgen, T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25, 402\u2013408 (2001).","journal-title":"Methods"},{"key":"2844_CR33","doi-asserted-by":"crossref","first-page":"15174","DOI":"10.1074\/jbc.M111.308023","volume":"287","author":"W Lei","year":"2012","unstructured":"Lei, W. et al. Progesterone and DNA damage encourage uterine cell proliferation and decidualization through up-regulating ribonucleotide reductase 2 expression during early pregnancy in mice. J. Biol. Chem. 287, 15174\u201315192 (2012).","journal-title":"J. Biol. Chem."},{"key":"2844_CR34","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1097\/01.ASN.0000132473.50966.14","volume":"15","author":"EM Freel","year":"2004","unstructured":"Freel, E. M. & Connell, J. M. Mechanisms of hypertension: the expanding role of aldosterone. J. Am. Soc. Nephrol. 15, 1993\u20132001 (2004).","journal-title":"J. Am. Soc. Nephrol."},{"key":"2844_CR35","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1210\/me.2012-1247","volume":"27","author":"K Kuroda","year":"2013","unstructured":"Kuroda, K. et al. Induction of 11beta-HSD 1 and activation of distinct mineralocorticoid receptor- and glucocorticoid receptor-dependent gene networks in decidualizing human endometrial stromal cells. Mol. Endocrinol. 27, 192\u2013202 (2013).","journal-title":"Mol. Endocrinol."},{"key":"2844_CR36","doi-asserted-by":"crossref","first-page":"7542","DOI":"10.1074\/jbc.M116.764449","volume":"292","author":"D Lavall","year":"2017","unstructured":"Lavall, D. et al. Rac1 GTPase regulates 11beta hydroxysteroid dehydrogenase type 2 and fibrotic remodeling. J. Boil. Chem. 292, 7542\u20137553 (2017).","journal-title":"J. Boil. Chem."},{"key":"2844_CR37","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1095\/biolreprod.102.009316","volume":"68","author":"JJ Kim","year":"2003","unstructured":"Kim, J. J. et al. Regulation of insulin-like growth factor binding protein-1 promoter activity by FKHR and HOXA10 in primate endometrial cells. Biol. Reprod. 68, 24\u201330 (2003).","journal-title":"Biol. Reprod."},{"key":"2844_CR38","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.tibs.2004.12.002","volume":"30","author":"LP van der Heide","year":"2005","unstructured":"van der Heide, L. P. & Smidt, M. P. Regulation of FoxO activity by CBP\/p300-mediated acetylation. Trends Biochem. Sci. 30, 81\u201386 (2005).","journal-title":"Trends Biochem. Sci."},{"key":"2844_CR39","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1530\/REP-11-0114","volume":"142","author":"AI Frolova","year":"2011","unstructured":"Frolova, A. I. & Moley, K. H. Glucose transporters in the uterus: an analysis of tissue distribution and proposed physiological roles. Reproduction 142, 211\u2013220 (2011).","journal-title":"Reproduction"},{"key":"2844_CR40","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.canlet.2014.01.031","volume":"356","author":"N Wong","year":"2015","unstructured":"Wong, N., Ojo, D., Yan, J. & Tang, D. PKM2 contributes to cancer metabolism. Cancer Lett. 356, 184\u2013191 (2015).","journal-title":"Cancer Lett."},{"key":"2844_CR41","doi-asserted-by":"crossref","first-page":"29739","DOI":"10.1074\/jbc.M114.584821","volume":"289","author":"Z Liu","year":"2014","unstructured":"Liu, Z. et al. PDK4 protein promotes tumorigenesis through activation of cAMP-response element-binding protein (CREB)-Ras homolog enriched in brain (RHEB)-mTORC1 signaling cascade. J. Biol. Chem. 289, 29739\u201329749 (2014).","journal-title":"J. Biol. Chem."},{"key":"2844_CR42","doi-asserted-by":"crossref","first-page":"4765","DOI":"10.1113\/JP270821","volume":"593","author":"AM Fritzen","year":"2015","unstructured":"Fritzen, A. M. et al. 5\u2032-AMP activated protein kinase alpha2 controls substrate metabolism during post-exercise recovery via regulation of pyruvate dehydrogenase kinase 4. J. Physiol. 593, 4765\u20134780 (2015).","journal-title":"J. Physiol."},{"key":"2844_CR43","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1007\/s00018-009-9066-x","volume":"66","author":"SM Houten","year":"2009","unstructured":"Houten, S. M. et al. Pyruvate dehydrogenase kinase 4 expression is synergistically induced by AMP-activated protein kinase and fatty acids. Cell. Mol. Life Sci. 66, 1283\u20131294 (2009).","journal-title":"Cell. Mol. Life Sci."},{"key":"2844_CR44","doi-asserted-by":"crossref","first-page":"4535","DOI":"10.7150\/thno.25674","volume":"8","author":"S Jiang","year":"2018","unstructured":"Jiang, S. et al. AMPK: potential therapeutic target for ischemic stroke. Theranostics 8, 4535\u20134551 (2018).","journal-title":"Theranostics"},{"key":"2844_CR45","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1210\/me.2011-0026","volume":"25","author":"AI Frolova","year":"2011","unstructured":"Frolova, A. I., O\u2019Neill, K. & Moley, K. H. Dehydroepiandrosterone inhibits glucose flux through the pentose phosphate pathway in human and mouse endometrial stromal cells, preventing decidualization and implantation. Mol. Endocrinol. 25, 1444\u20131455 (2011).","journal-title":"Mol. Endocrinol."},{"key":"2844_CR46","doi-asserted-by":"crossref","unstructured":"Herr, D., Bekes, I. & Wulff, C. Local renin-angiotensin system in the reproductive system. Front. Endocrinol. 4, 150 (2013)","DOI":"10.3389\/fendo.2013.00150"},{"key":"2844_CR47","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1530\/EC-16-0082","volume":"6","author":"SJ Delforce","year":"2017","unstructured":"Delforce, S. J. et al. Expression of renin-angiotensin system (RAS) components in endometrial cancer. Endocr. Connect. 6, 9\u201319 (2017).","journal-title":"Endocr. Connect."},{"key":"2844_CR48","doi-asserted-by":"crossref","first-page":"R91","DOI":"10.1152\/ajpregu.00034.2013","volume":"306","author":"ER Lumbers","year":"2014","unstructured":"Lumbers, E. R. & Pringle, K. G. Roles of the circulating renin-angiotensin-aldosterone system in human pregnancy. Am. J. Physiol. Regul. Integr. Comp. Physiol. 306, R91\u2013101 (2014).","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"2844_CR49","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s00424-012-1145-4","volume":"464","author":"A Todkar","year":"2012","unstructured":"Todkar, A. et al. Aldosterone deficiency adversely affects pregnancy outcome in mice. Pflug. Arch. 464, 331\u2013343 (2012).","journal-title":"Pflug. Arch."},{"key":"2844_CR50","first-page":"318","volume":"46","author":"G Nicolini","year":"2014","unstructured":"Nicolini, G. et al. LH, progesterone, and TSH can stimulate aldosterone in vitro: a study on normal adrenal cortex and aldosterone producing adenoma. Horm. Metab. Res. 46, 318\u2013321 (2014).","journal-title":"Horm. Metab. Res."},{"key":"2844_CR51","doi-asserted-by":"crossref","first-page":"3981","DOI":"10.1210\/jc.2006-1154","volume":"91","author":"ED Szmuilowicz","year":"2006","unstructured":"Szmuilowicz, E. D. et al. Relationship between aldosterone and progesterone in the human menstrual cycle. J. Clin. Endocrinol. Metab. 91, 3981\u20133987 (2006).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2844_CR52","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1161\/HYPERTENSIONAHA.119.12924","volume":"74","author":"A Birukov","year":"2019","unstructured":"Birukov, A. et al. Aldosterone, salt, and potassium intakes as predictors of pregnancy outcome, including preeclampsia. Hypertension 74, 391\u2013398 (2019).","journal-title":"Hypertension"},{"key":"2844_CR53","doi-asserted-by":"crossref","first-page":"138","DOI":"10.3349\/ymj.2008.49.1.138","volume":"49","author":"EH Kim","year":"2008","unstructured":"Kim, E. H., Lim, J. H., Kim, Y. H. & Park, Y. W. The relationship between aldosterone to renin ratio and RI value of the uterine artery in the preeclamptic patient vs. normal pregnancy. Yonsei Med. J. 49, 138\u2013143 (2008).","journal-title":"Yonsei Med. J."},{"key":"2844_CR54","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.placenta.2017.06.005","volume":"60","author":"KP Conrad","year":"2017","unstructured":"Conrad, K. P., Rabaglino, M. B. & Post Uiterweer, E. D. Emerging role for dysregulated decidualization in the genesis of preeclampsia. Placenta 60, 119\u2013129 (2017).","journal-title":"Placenta"},{"key":"2844_CR55","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.mce.2005.12.010","volume":"248","author":"SE McDonald","year":"2006","unstructured":"McDonald, S. E., Henderson, T. A., Gomez-Sanchez, C. E., Critchley, H. O. & Mason, J. I. 11Beta-hydroxysteroid dehydrogenases in human endometrium. Mol. Cell. Endocrinol. 248, 72\u201378 (2006).","journal-title":"Mol. Cell. Endocrinol."},{"key":"2844_CR56","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1146\/annurev.med.48.1.231","volume":"48","author":"JW Funder","year":"1997","unstructured":"Funder, J. W. Glucocorticoid and mineralocorticoid receptors: biology and clinical relevance. Annu Rev. Med. 48, 231\u2013240 (1997).","journal-title":"Annu Rev. Med."},{"key":"2844_CR57","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1152\/physrev.00020.2012","volume":"93","author":"K Chapman","year":"2013","unstructured":"Chapman, K., Holmes, M. & Seckl, J. 11beta-hydroxysteroid dehydrogenases: intracellular gate-keepers of tissue glucocorticoid action. Physiol. Rev. 93, 1139\u20131206 (2013).","journal-title":"Physiol. Rev."},{"key":"2844_CR58","doi-asserted-by":"crossref","first-page":"28484","DOI":"10.1074\/jbc.M100374200","volume":"276","author":"A Odermatt","year":"2001","unstructured":"Odermatt, A., Arnold, P. & Frey, F. J. The intracellular localization of the mineralocorticoid receptor is regulated by 11beta-hydroxysteroid dehydrogenase type 2. J. Biol. Chem. 276, 28484\u201328492 (2001).","journal-title":"J. Biol. Chem."},{"key":"2844_CR59","doi-asserted-by":"crossref","first-page":"T83","DOI":"10.1530\/JOE-17-0155","volume":"234","author":"TJ Cole","year":"2017","unstructured":"Cole, T. J. & Young, M. J. 30 years of the mineralcorticoid receptor: mineralocorticoid receptor null mice: informing cell-type-specific roles. J. Endocrinol. 234, T83\u2013T92 (2017).","journal-title":"J. Endocrinol."},{"key":"2844_CR60","doi-asserted-by":"crossref","first-page":"E224","DOI":"10.1210\/jc.2010-0154","volume":"95","author":"V Bombail","year":"2010","unstructured":"Bombail, V. et al. A Role for the orphan nuclear receptor estrogen-related receptor alpha in endometrial stromal cell decidualization and expression of genes implicated in energy metabolism. J. Clin. Endocrinol. Metab. 95, E224\u2013228 (2010).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2844_CR61","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.tem.2018.09.007","volume":"29","author":"K Sakamoto","year":"2018","unstructured":"Sakamoto, K., Bultot, L. & Goransson, O. The salt-inducible kinases: Emerging metabolic regulators. Trends Endocrinol. Metab. 29, 827\u2013840 (2018).","journal-title":"Trends Endocrinol. Metab."},{"key":"2844_CR62","doi-asserted-by":"crossref","first-page":"1204598","DOI":"10.1155\/2018\/1204598","volume":"2018","author":"A Cannavo","year":"2018","unstructured":"Cannavo, A. et al. Aldosterone and mineralocorticoid receptor system in cardiovascular physiology and pathophysiology. Oxid. Med. Cell. Longev. 2018, 1204598 (2018).","journal-title":"Oxid. Med. Cell. Longev."},{"key":"2844_CR63","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1159\/000447834","volume":"39","author":"MS Salker","year":"2016","unstructured":"Salker, M. S. et al. LEFTYA activates the epithelial Na+ channel (ENaC) in endometrial cells via serum and glucocorticoid inducible kinase SGK1. Cell. Physiol. Biochem. 39, 1295\u20131306 (2016).","journal-title":"Cell. Physiol. Biochem."},{"key":"2844_CR64","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1530\/REP-14-0386","volume":"148","author":"X Sun","year":"2014","unstructured":"Sun, X. et al. Regulation of miR-101\/miR-199a-3p by the epithelial sodium channel during embryo implantation: involvement of CREB phosphorylation. Reproduction 148, 559\u2013568 (2014).","journal-title":"Reproduction"}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41419-020-02844-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-020-02844-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-020-02844-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T15:13:41Z","timestamp":1670253221000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41419-020-02844-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,13]]},"references-count":64,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["2844"],"URL":"https:\/\/doi.org\/10.1038\/s41419-020-02844-9","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,13]]},"assertion":[{"value":"30 January 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 July 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 July 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 August 2020","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"679"}}