Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Article Sex Dev DOI: 10.1159/000252813 Insulin Receptor and IGF1R Are Not Required for Oocyte Growth, Differentiation, and Maturation in Mice J.L. Pitetti a D. Torre a B. Conne a M.D. Papaioannou a C.R. Cederroth a S. Xuan b R. Kahn c L.F. Parada d J.D. Vassalli a A. Efstratiadis b S. Nef a a Department of Genetic Medicine and Development, University of Geneva Medical School, University of Geneva, Geneva, Switzerland; b Department of Genetics and Development, Columbia University Medical Center, New York, N.Y., c Joslin Diabetes Center and Harvard Medical School, Boston, Mass., d Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, Tex., USA and litter size. In view of these novel observations indicating that the insulin/IGF signaling is not essential in oocytes, the IGF1-dependent female fertility is re-evaluated and dis- cussed. Copyright © 2009 S. Karger AG, Basel Mammalian oocytes are highly specialized cells which undergo meiosis and monospermic fertilization. As a consequence, sperm chromatin is reprogrammed into a functional pronucleus, zygotic genome activation is in- duced, and early embryonic development commences. This developmental potential is acquired during oogen- esis and requires the coordinate action of both circulating hormones and locally derived factors that are essential for follicular development including recruitment, selection, and dominance [for review see van den Hurk and Zhao, 2005]. In particular, progression through the successive stages of follicular development requires bi-directional communication between the oocyte and granulosa cells Key Words Differentiation  Fertility  Growth  Igf1r  Insr  Maturation  Mouse  Oozyte Abstract In mammals, insulin and insulin-like growth factors (IGFs: IGF1 and IGF2) act through 2 structurally related receptors, the insulin receptor (INSR) and the type 1 IGF receptor (IGF1R), both of which are expressed in developing oocytes. IGF1 plays an important role in female reproduction, and fe- male Igf1 knockout mice fail to ovulate and are infertile. On the other hand, little is known about the in vivo role of the insulin signaling pathway in oocytes during follicular devel- opment, although exposure to insulin or IGF1 in vitro im- proves oocyte maturation. To further address the signifi- cance of insulin/IGF signaling, we used conditional mutant mice and ablated the function of the genes encoding INSR, IGF1R, or both receptors specifically in developing mouse oocytes. Our genetic evidence showed unexpectedly that the female reproductive functions are not affected when Insr , Igf1r or both Insr;Igf1r are ablated in oocytes, as the fe- male mice are fertile and exhibit normal estrous cyclicity, oo- cyte development and maturation, parturition frequency, Received: January 29, 2009 Accepted: June 25, 2009 Published online: October 23, 2009 Serge Nef Department of Genetic Medicine and Development University of Geneva Medical School 1, rue Michel-Servet, CH–1211 Geneva 4 (Switzerland) Tel. +41 22 379 5193, Fax +41 22 379 5260, E-Mail serge.nef @ unige.ch © 2009 S. Karger AG, Basel 1661–5425/09/0000–0000$26.00/0 Accessible online at: www.karger.com/sxd J.L.P. and D.T. contributed equally to this work.