This Article Full Text Full Text (PDF) All Versions of this Article: 22/3/665    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Rantakari, P. Articles by Poutanen, M. Search for Related Content PubMed PubMed Citation Articles by Rantakari, P. Articles by Poutanen, M.

Placenta Defects and Embryonic Lethality Resulting from Disruption of Mouse Hydroxysteroid (17-β) Dehydrogenase 2 Gene

Department of Physiology (P.R., L.S., H.L., J.P., P.P., M.P.), Medical Biochemistry (R.K.) and Department of Pharmacology, Drug Development and Therapeutics (I.H.), Institute of Biomedicine, University of Turku, FIN-20520 Turku, Finland; and Biocenter Oulu, Laboratory of Developmental Biology and Department of Medical Biochemistry and Molecular Biology (S.V.), University of Oulu, FIN-90014 Oulu, Finland

Address all correspondence and requests for reprints to: Professor Matti Poutanen, Department of Physiology, Institute of Biomedicine, University of Turku, FIN-20520 Turku, Finland. E-mail: matti.poutanen{at}utu.fi.

Hydroxysteroid (17-β) dehydrogenase 2 (HSD17B2) is a member of aldo-keto reductase superfamily, known to catalyze the inactivation of 17β-hydroxysteroids to less active 17-keto forms and catalyze the conversion of 20-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.