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Genes involved in conceptus–endometrial interactions in ruminants: insights from reductionism and thoughts on holistic approaches

Department of Animal Science, Center for Animal Biotechnology and Genomics, Texas A&M University, College Station, Texas 77843, USA¹ Institut National de la Recherche Agronomique, UMR 1198 INRA-ENVA Biologie du Développement et de la Reproduction, 78352 Jouy-en-Josas Cedex, France² Institute of Molecular Animal Breeding and Biotechnology and ³ Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, Ludwig-Maximilians University, Munich, Germany

Correspondence should be addressed to T E Spencer; Email: tspencer{at}tamu.edu) (ewolf{at}lmb.uni-muenchen.de

(tspencer{at}tamu.edu) (ewolf{at}lmb.uni-muenchen.de)

This review summarizes new knowledge on expression of genes and provides insights into approaches for study of conceptus–endometrial interactions in ruminants with emphasis on the peri-implantation stage of pregnancy. Conceptus–endometrial interactions in ruminants are complex and involve carefully orchestrated temporal and spatial alterations in gene expression regulated by hormones from the ovary and conceptus. Progesterone is the hormone of pregnancy and acts on the uterus to stimulate blastocyst survival, growth, and development. Inadequate progesterone levels or a delayed rise in progesterone is associated with pregnancy loss. The mononuclear trophectoderm cells of the elongating blastocyst synthesize and secrete interferon- (IFNT), the pregnancy recognition signal. Trophoblast giant binucleate cells begin to differentiate and produce hormones including chorionic somatomammotropin 1 (CSH1 or placental lactogen). A number of genes, induced or stimulated by progesterone, IFNT, and/or CSH1 in a cell-specific manner, are implicated in trophectoderm adhesion to the endometrial luminal epithelium and regulation of conceptus growth and differentiation. Transcriptional profiling experiments are beginning to unravel the complex dynamics of conceptus–endometrial interactions in cattle and sheep. Future experiments should incorporate physiological models of pregnancy loss and be complemented by metabolomic studies of uterine lumen contents to more completely define factors required for blastocyst survival, growth, and implantation. Both reduction and holistic approaches will be important to understand the multifactorial phenomenon of recurrent pregnancy loss and provide a basis for new strategies to improve pregnancy outcome and reproductive efficiency in cattle and other domestic animals.

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