{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T03:54:01Z","timestamp":1787975641230,"version":"build-2784847793"},"reference-count":52,"publisher":"The Endocrine Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hydroxysteroid (17-\u03b2) dehydrogenase 2 (HSD17B2) is a member of aldo-keto reductase superfamily, known to catalyze the inactivation of 17\u03b2-hydroxysteroids to less active 17-keto forms and catalyze the conversion of 20\u03b1-hydroxyprogesterone to progesterone in vitro. To examine the role of HSD17B2 in vivo, we generated mice deficient in Hsd17b2 [HSD17B2 knockout (KO)] by a targeted gene disruption in embryonic stem cells. From the homozygous mice carrying the disrupted Hsd17b2, 70% showed embryonic lethality appearing at the age of embryonic d 11.5 onward. The embryonic lethality was associated with reduced placental size measured at embryonic d 17.5. The HSD17B2KO mice placentas presented with structural abnormalities in all three major layers: the decidua, spongiotrophoblast, and labyrinth. Most notable was the disruption of the spongiotrophoblast and labyrinthine layers, together with liquid-filled cysts in the junctional region and the basal layer. Treatments with an antiestrogen or progesterone did not rescue the embryonic lethality or the placenta defect in the homozygous mice. In hybrid background used, 24% of HSD17B2KO mice survived through the fetal period but were born growth retarded and displayed a phenotype in the brain with enlargement of ventricles, abnormal laminar organization, and increased cellular density in the cortex. Furthermore, the HSD17B2KO mice had unilateral renal degeneration, the affected kidney frequently appearing as a fluid-filled sac. Our results provide evidence for a role for HSD17B2 enzyme in the cellular organization of the mouse placenta.<\/jats:p>","DOI":"10.1210\/me.2007-0257","type":"journal-article","created":{"date-parts":[[2007,11,30]],"date-time":"2007-11-30T02:00:26Z","timestamp":1196388026000},"page":"665-675","source":"Crossref","is-referenced-by-count":27,"title":["Placenta Defects and Embryonic Lethality Resulting from Disruption of Mouse Hydroxysteroid (17-\u03b2) Dehydrogenase 2 Gene"],"prefix":"10.1210","volume":"22","author":[{"given":"Pia","family":"Rantakari","sequence":"first","affiliation":[{"name":"Department of Physiology (P.R., L.S., H.L., J.P., P.P., M.P.), FIN-20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leena","family":"Strauss","sequence":"additional","affiliation":[{"name":"Department of Physiology (P.R., L.S., H.L., J.P., P.P., M.P.), FIN-20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riku","family":"Kiviranta","sequence":"additional","affiliation":[{"name":"Medical Biochemistry (R.K.), FIN-20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Lagerbohm","sequence":"additional","affiliation":[{"name":"Department of Physiology (P.R., L.S., H.L., J.P., P.P., M.P.), FIN-20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenni","family":"Paviala","sequence":"additional","affiliation":[{"name":"Department of Physiology (P.R., L.S., H.L., J.P., P.P., M.P.), FIN-20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irma","family":"Holopainen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Drug Development and Therapeutics (I.H.), Institute of Biomedicine, University of Turku, FIN-20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seppo","family":"Vainio","sequence":"additional","affiliation":[{"name":"Biocenter Oulu, Laboratory of Developmental Biology and Department of Medical Biochemistry and Molecular Biology (S.V.), University of Oulu, FIN-90014 Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pirjo","family":"Pakarinen","sequence":"additional","affiliation":[{"name":"Department of Physiology (P.R., L.S., H.L., J.P., P.P., M.P.), FIN-20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matti","family":"Poutanen","sequence":"additional","affiliation":[{"name":"Department of Physiology (P.R., L.S., H.L., J.P., P.P., M.P.), FIN-20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071614160763900_R1","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/S0039-128X(96)00174-2","article-title":"The key role of 17\u03b2-hydroxysteroid dehydrogenases in sex steroid biology.","volume":"62","author":"Labrie","year":"1997","journal-title":"Steroids"},{"key":"2020071614160763900_R2","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/0960-0760(95)00209-X","article-title":"Characteristics of human types 1, 2 and 3 17\u03b2-hydroxysteroid dehydrogenase activities: oxidation\/reduction and inhibition.","volume":"55","author":"Luu-The","year":"1995","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2020071614160763900_R3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1677\/jme.0.0230001","article-title":"17\u03b2-hydroxysteroid dehydrogenase (HSD)\/17-ketosteroid reductase (KSR) family; nomenclature and main characteristics of the 17HSD\/KSR enzymes.","volume":"23","author":"Peltoketo","year":"1999","journal-title":"J Mol Endocrinol"},{"key":"2020071614160763900_R4","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0960-0760(00)00155-2","article-title":"Analysis and characteristics of multiple types of human 17\u03b2-hydroxysteroid dehydrogenase.","volume":"76","author":"Luu-The","year":"2001","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2020071614160763900_R5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1677\/jme.0.0250001","article-title":"Intracrinology: role of the family of 17\u03b2-hydroxysteroid dehydrogenases in human physiology and disease.","volume":"25","author":"Labrie","year":"2000","journal-title":"J Mol Endocrinol"},{"key":"2020071614160763900_R6","doi-asserted-by":"crossref","first-page":"16329","DOI":"10.1074\/jbc.M001994200","article-title":"Inactivation of the peroxisomal multifunctional protein-2 in mice impedes the degradation of not only 2-methyl-branched fatty acids and bile acid intermediates but also of very long chain fatty acids.","volume":"275","author":"Baes","year":"2000","journal-title":"J Biol Chem"},{"key":"2020071614160763900_R7","doi-asserted-by":"crossref","first-page":"15014","DOI":"10.1074\/jbc.274.21.15014","article-title":"Human brain short chain L-3-hydroxyacyl coenzyme A dehydrogenase is a single-domain multifunctional enzyme. Characterization of a novel 17\u03b2-hydroxysteroid dehydrogenase.","volume":"274","author":"He","year":"1999","journal-title":"J Biol Chem"},{"key":"2020071614160763900_R8","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/0303-7207(94)90004-3","article-title":"Compartmentalization of type I 17\u03b2-hydroxysteroid oxidoreductase in the human ovary.","volume":"99","author":"Sawetawan","year":"1994","journal-title":"Mol Cell Endocrinol"},{"key":"2020071614160763900_R9","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1677\/joe.0.1430139","article-title":"Expression of 17\u03b2-hydroxysteroid dehydrogenase in human granulosa cells: correlation with follicular size, cytochrome P450 aromatase activity and oestradiol production.","volume":"143","author":"Ghersevich","year":"1994","journal-title":"J Endocrinol"},{"key":"2020071614160763900_R10","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1677\/joe.0.1400409","article-title":"Expression of 17\u03b2-hydroxysteroid dehydrogenase in the rat ovary during follicular development and luteinization induced with pregnant mare serum gonadotrophin and human chorionic gonadotrophin.","volume":"140","author":"Ghersevich","year":"1994","journal-title":"J Endocrinol"},{"key":"2020071614160763900_R11","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/ng0594-34","article-title":"Male pseudohermaphroditism caused by mutations of testicular 17 \u03b2-hydroxysteroid dehydrogenase 3.","volume":"7","author":"Geissler","year":"1994","journal-title":"Nat Genet"},{"key":"2020071614160763900_R12","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1023\/A:1006217400137","article-title":"17\u03b2-Hydroxysteroid dehydrogenases in normal human mammary epithelial cells and breast tissue.","volume":"57","author":"Miettinen","year":"1999","journal-title":"Breast Cancer Res Treat"},{"key":"2020071614160763900_R13","first-page":"582","article-title":"Immunohistochemical localization of 17\u03b2-hydroxysteroid dehydrogenase in the human endometrium during the menstrual cycle.","volume":"65","author":"Maentausta","year":"1991","journal-title":"Lab Invest"},{"key":"2020071614160763900_R14","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/S1043-2760(00)00342-8","article-title":"Role of 17\u03b2-hydroxysteroid dehydrogenases in sex steroid formation in peripheral intracrine tissues.","volume":"11","author":"Labrie","year":"2000","journal-title":"Trends Endocrinol Metab"},{"key":"2020071614160763900_R15","doi-asserted-by":"crossref","first-page":"12964","DOI":"10.1016\/S0021-9258(18)31480-7","article-title":"Expression cloning and characterization of human 17\u03b2-hydroxysteroid dehydrogenase type 2, a microsomal enzyme possessing 20\u03b1-hydroxysteroid dehydrogenase activity.","volume":"268","author":"Wu","year":"1993","journal-title":"J Biol Chem"},{"key":"2020071614160763900_R16","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1089\/dna.1995.14.849","article-title":"The human type II 17\u03b2-hydroxysteroid dehydrogenase gene encodes two alternatively spliced mRNA species.","volume":"14","author":"Labrie","year":"1995","journal-title":"DNA Cell Biol"},{"key":"2020071614160763900_R17","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1677\/jme.0.0200067","article-title":"Mouse 17\u03b2-hydroxysteroid dehydrogenase type 2 mRNA is predominantly expressed in hepatocytes and in surface epithelial cells of the gastrointestinal and urinary tracts.","volume":"20","author":"Mustonen","year":"1998","journal-title":"J Mol Endocrinol"},{"key":"2020071614160763900_R18","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1042\/cs1010485","article-title":"17\u03b2-Hydroxysteroid dehydrogenase type 2 expression and enzyme activity in the human gastrointestinal tract.","volume":"101","author":"Sano","year":"2001","journal-title":"Clin Sci (Lond)"},{"key":"2020071614160763900_R19","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0303-7207(97)00157-3","article-title":"Ontogeny of 17\u03b2-hydroxysteroid dehydrogenase type 2 mRNA expression in the developing mouse placenta and fetus.","volume":"134","author":"Mustonen","year":"1997","journal-title":"Mol Cell Endocrinol"},{"key":"2020071614160763900_R20","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1172\/JCI117569","article-title":"17 \u03b2-Hydroxysteroid dehydrogenase type 2: chromosomal assignment and progestin regulation of gene expression in human endometrium.","volume":"94","author":"Casey","year":"1994","journal-title":"J Clin Invest"},{"key":"2020071614160763900_R21","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1002\/(SICI)1097-0215(19960328)66:1<37::AID-IJC7>3.0.CO;2-#","article-title":"Characterization of 17\u03b2-hydroxysteroid dehydrogenase isoenzyme expression in benign and malignant human prostate.","volume":"66","author":"Elo","year":"1996","journal-title":"Int J Cancer"},{"key":"2020071614160763900_R22","doi-asserted-by":"crossref","first-page":"3827","DOI":"10.1210\/en.2007-0365","article-title":"Transgenic male mice expressing human hydroxysteroid (17\u03b2) dehydrogenase 2 indicate a role for the enzyme independent of its action on sex steroids.","volume":"148","author":"Zhongyi","year":"2007","journal-title":"Endocrinology"},{"key":"2020071614160763900_R23","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1101\/gad.2.12a.1639","article-title":"Isolation and characterization of a novel trophoblast-specific cDNA in the mouse.","volume":"2","author":"Lescisin","year":"1988","journal-title":"Genes Dev"},{"key":"2020071614160763900_R24","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1210\/mend-1-11-767","article-title":"Molecular cloning and expression of mouse placental lactogen I complementary deoxyribonucleic acid.","volume":"1","author":"Colosi","year":"1987","journal-title":"Mol Endocrinol"},{"key":"2020071614160763900_R25","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1006\/dbio.1997.8640","article-title":"Esx1, a novel X chromosome-linked homeobox gene expressed in mouse extraembryonic tissues and male germ cells.","volume":"188","author":"Li","year":"1997","journal-title":"Dev Biol"},{"key":"2020071614160763900_R26","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/nm1184","article-title":"Spontaneous fetal loss caused by placental thrombosis in estrogen sulfotransferase-deficient mice.","volume":"11","author":"Tong","year":"2005","journal-title":"Nat Med"},{"key":"2020071614160763900_R27","first-page":"917","article-title":"Fetal death in mice lacking 5\u03b1-reductase type 1 caused by estrogen excess.","volume":"11","author":"Mahendroo","year":"1997","journal-title":"Mol Endocrinol"},{"key":"2020071614160763900_R28","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1101\/gad.9.18.2266","article-title":"Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities.","volume":"9","author":"Lydon","year":"1995","journal-title":"Genes Dev"},{"key":"2020071614160763900_R29","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/mrdd.1024","article-title":"Neuronal migration disorders.","volume":"7","author":"Gleeson","year":"2001","journal-title":"Ment Retard Dev Disabil Res Rev"},{"key":"2020071614160763900_R30","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/ajmg.1569","article-title":"Epilepsy and genetic malformations of the cerebral cortex.","volume":"106","author":"Guerrini","year":"2001","journal-title":"Am J Med Genet"},{"key":"2020071614160763900_R31","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/362065a0","article-title":"Deregulation of Pax-2 expression in transgenic mice generates severe kidney abnormalities.","volume":"362","author":"Dressler","year":"1993","journal-title":"Nature"},{"key":"2020071614160763900_R32","doi-asserted-by":"crossref","first-page":"2392","DOI":"10.1073\/pnas.0308703100","article-title":"Loss of NFAT5 results in renal atrophy and lack of tonicity-responsive gene expression.","volume":"101","author":"Lopez-Rodriguez","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071614160763900_R33","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1034\/j.1399-0004.2003.00127.x","article-title":"The genetics of pre-eclampsia: a feto-placental or maternal problem?","volume":"64","author":"Cross","year":"2003","journal-title":"Clin Genet"},{"key":"2020071614160763900_R34","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1161\/hy02t2.102904","article-title":"Discovery of a spontaneous genetic mouse model of preeclampsia.","volume":"39","author":"Davisson","year":"2002","journal-title":"Hypertension"},{"key":"2020071614160763900_R35","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1073\/pnas.242735799","article-title":"Estrogen receptor (ER)\u03b2 knockout mice reveal a role for ER\u03b2 in migration of cortical neurons in the developing brain.","volume":"100","author":"Wang","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071614160763900_R36","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1128\/MCB.22.8.2769-2776.2002","article-title":"Hydrocephalus, situs inversus, chronic sinusitis, and male infertility in DNA polymerase \u03bb-deficient mice: possible implication for the pathogenesis of immotile cilia syndrome.","volume":"22","author":"Kobayashi","year":"2002","journal-title":"Mol Cell Biol"},{"key":"2020071614160763900_R37","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1126\/science.1093889","article-title":"Modulation of Th1 activation and inflammation by the NF-\u03baB repressor Foxj1.","volume":"303","author":"Lin","year":"2004","journal-title":"Science"},{"key":"2020071614160763900_R38","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1083\/jcb.200312107","article-title":"Brain development in mice lacking L1\u2013L1 homophilic adhesion.","volume":"165","author":"Itoh","year":"2004","journal-title":"J Cell Biol"},{"key":"2020071614160763900_R39","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/S0960-0760(98)00064-8","article-title":"Evolution of mammalian 11\u03b2- and 17\u03b2-hydroxysteroid dehydrogenases-type 2 and retinol dehydrogenases from ancestors in Caenorhabditis elegans and evidence for horizontal transfer of a eukaryote dehydrogenase to E. coli.","volume":"66","author":"Baker","year":"1998","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2020071614160763900_R40","doi-asserted-by":"crossref","first-page":"3900","DOI":"10.1074\/jbc.270.8.3900","article-title":"Cloning of a cDNA for liver microsomal retinol dehydrogenase. A tissue-specific, short-chain alcohol dehydrogenase.","volume":"270","author":"Chai","year":"1995","journal-title":"J Biol Chem"},{"key":"2020071614160763900_R41","doi-asserted-by":"crossref","first-page":"28408","DOI":"10.1074\/jbc.270.47.28408","article-title":"Cloning of a cDNA for a second retinol dehydrogenase type II. Expression of its mRNA relative to type I.","volume":"270","author":"Chai","year":"1995","journal-title":"J Biol Chem"},{"key":"2020071614160763900_R42","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1074\/jbc.270.3.1107","article-title":"The retinal pigment epithelial-specific 11-cis retinol dehydrogenase belongs to the family of short chain alcohol dehydrogenases.","volume":"270","author":"Simon","year":"1995","journal-title":"J Biol Chem"},{"key":"2020071614160763900_R43","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1038\/7788","article-title":"Embryonic retinoic acid synthesis is essential for early mouse post-implantation development.","volume":"21","author":"Niederreither","year":"1999","journal-title":"Nat Genet"},{"key":"2020071614160763900_R44","doi-asserted-by":"crossref","first-page":"4269","DOI":"10.1210\/endo.139.10.6272","article-title":"The effect of 9-cis-retinoic acid on proliferation and differentiation of a spermatogonia and retinoid receptor gene expression in the vitamin A-deficient mouse testis.","volume":"139","author":"Gaemers","year":"1998","journal-title":"Endocrinology"},{"key":"2020071614160763900_R45","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1095\/biolreprod58.6.1351","article-title":"Differential expression pattern of retinoid X receptors in adult murine testicular cells implies varying roles for these receptors in spermatogenesis.","volume":"58","author":"Gaemers","year":"1998","journal-title":"Biol Reprod"},{"key":"2020071614160763900_R46","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.1242\/dev.120.10.2723","article-title":"Function of the retinoic acid receptors (RARs) during development (I). Craniofacial and skeletal abnormalities in RAR double mutants.","volume":"120","author":"Lohnes","year":"1994","journal-title":"Development"},{"key":"2020071614160763900_R47","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1126\/science.117.3046.535","article-title":"Excessive intake of vitamin A as a cause of congenital anomalies in the rat.","volume":"117","author":"Cohlan","year":"1953","journal-title":"Science"},{"key":"2020071614160763900_R48","first-page":"2721","article-title":"Retinoid receptors in the human endometrium and its disorders: a possible modulator of 17\u03b2-hydroxysteroid dehydrogenase.","volume":"86","author":"Ito","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071614160763900_R49","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/2417","article-title":"A new logic for DNA engineering using recombination in Escherichia coli.","volume":"20","author":"Zhang","year":"1998","journal-title":"Nat Genet"},{"key":"2020071614160763900_R50","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1038\/82449","article-title":"DNA cloning by homologous recombination in Escherichia coli.","volume":"18","author":"Zhang","year":"2000","journal-title":"Nat Biotechnol"},{"key":"2020071614160763900_R51","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1093\/nar\/27.6.1555","article-title":"Rapid modification of bacterial artificial chromosomes by ET-recombination.","volume":"27","author":"Muyrers","year":"1999","journal-title":"Nucleic Acids Res"},{"key":"2020071614160763900_R52","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1210\/jcem-61-4-698","article-title":"Treatment of prostatic cancer with a gonadotropin-releasing hormone agonist analog: acute and long term effects on endocrine functions of testis tissue.","volume":"61","author":"Huhtaniemi","year":"1985","journal-title":"J Clin Endocrinol Metab"}],"container-title":["Molecular Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/mend\/article-pdf\/22\/3\/665\/10721245\/mend0665.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/mend\/article-pdf\/22\/3\/665\/10721245\/mend0665.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,29]],"date-time":"2021-08-29T11:31:25Z","timestamp":1630236685000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/mend\/article\/22\/3\/665\/2661283"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,3,1]]},"references-count":52,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2008,3,1]]}},"URL":"https:\/\/doi.org\/10.1210\/me.2007-0257","relation":{},"ISSN":["0888-8809","1944-9917"],"issn-type":[{"value":"0888-8809","type":"print"},{"value":"1944-9917","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,3,1]]}}}