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Monozygotic Twin Model Reveals Novel Embryo-Induced Transcriptome Changes of Bovine Endometrium in the Preattachment Period¹

Institute of Molecular Animal Breeding and Biotechnology,⁴ Laboratory for Functional Genome Analysis,⁵ Gene Center, Ludwig-Maximilians University, 81377 Munich, Germany Physiology-Weihenstephan,⁶ Technical University of Munich, 85354 Freising, Germany Institute of Veterinary Biochemistry,⁷ Free University of Berlin, 14163 Berlin, Germany Institute of Animal Breeding,⁸ Bavarian Research Center for Agriculture, 85586 Grub, Germany Institute of Veterinary Anatomy, Histology and Embryology,⁹ Ludwig-Maximilians University, 80539 Munich, Germany

ABSTRACT

Initiation and maintenance of pregnancy are critically dependent on an intact embryo-maternal communication in the preimplantation period. To get new insights into molecular mechanisms underlying this complex dialog, a holistic transcriptome study of endometrium samples from Day 18 pregnant vs. nonpregnant twin cows was performed. This genetically defined model system facilitated the identification of specific conceptus-induced changes of the endometrium transcriptome. Using a combination of subtracted cDNA libraries and cDNA array hybridization, 87 different genes were identified as upregulated in pregnant animals. Almost one half of these genes are known to be stimulated by type I interferons. For the ISG15ylation system, which is assumed to play an important role in interferon tau (IFNT) signaling, mRNAs of four potential components (IFITM1, IFITM3, HSXIAPAF1, and DTX3L) were found at increased levels in addition to ISG15 and UBE1L. These results were further substantiated by colocalization of these mRNAs in the endometrium of pregnant animals shown by in situ hybridization. A functional classification of the identified genes revealed several different biological processes involved in the preparation of the endometrium for the attachment and implantation of the embryo. Specifically, elevated transcript levels were found for genes involved in modulation of the maternal immune system, genes relevant for cell adhesion, and for remodeling of the endometrium. This first systematic study of maternal transcriptome changes in response to the presence of an embryo on Day 18 of pregnancy in cattle is an important step toward deciphering the embryo-maternal dialog using a systems biology approach.

Bos taurus, conceptus, embryo-maternal cross talk, gene regulation, implantation, microarray, pregnancy, SSH, uterus

¹ Supported by the Deutsche Forschungsgemeinschaft (FOR 478/1) and the H. Wilhelm Schaumann Stiftung.

² Correspondence: FAX: 49 89 218076849; ewolf{at}lmb.uni-muenchen.de

³ These authors contributed equally to this work.

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