Decline in fertility of high-producing dairy cattle has become a global challenge to the dairy industry. Because of low heritability and complexity, it is difficult to find genetic markers for fertility traits in cattle. Here, we report the use of an in vitro fertilization (IVF) system and candidate gene approach to test genetic associations of a single-nucleotide polymorphism (SNP) in bovine placental lactogen (bPL), and its interactions with SNPs in the prolactin receptor (PRLR) and growth hormone receptor genes with fertility traits in an IVF system. The associations suggest a possible involvement of genetic interactions between bPL and PRLR in the fertilization and embryonic development processes, and the potential for application in a markerassisted selection program.Keywords: bovine placental lactogen, candidate gene, fertility, epistasis ImplicationsFertility of the modern high-producing dairy cow has been decreasing for the last 30 to 50 years and has become a major concern of farmers and the dairy industry worldwide. Many reasons account for this reduced reproductive efficiency, but the most important component seems to be a reduction in embryonic survival and fertilization rates. As such, there is an urgent need to identify the genetic factors responsible for the decline in embryo survival. Identifying these factors would enable reduction in the frequency of the deleterious alleles at these loci by marker-or gene-assisted selection. IntroductionThere is growing concern with the decline in reproductive efficiency in high-producing dairy cows (Royal et al., 2008). A variety of reasons have been proposed to account for infertility in cattle, including genetic factors, nutrition, physiology and management (Lucy, 2001;Veerkamp and Beerda, 2007). It is of particular interest to identify polymorphisms among specific genes and/or interactions between them that are associated with infertility in cattle, as this not only helps to elucidate the biology of infertility, but also provides genetic markers for use in marker-assisted selection.Although heritability is generally low, there is substantial genetic variation for fertility traits (Veerkamp and Beerda, 2007), enabling possible identification of genetic factors. However, owing to the complex nature of fertility, it is very challenging to find significant associations between genetic polymorphisms and fertility traits. An in vitro fertilization (IVF) system has the advantage of a unified environment and well-isolated components of the embryonic development process. Indeed, using an IVF system developed in our laboratory, single-nucleotide polymorphisms (SNPs) in several genes have been successfully shown to be associated with fertilization rate and early embryonic survival rate (Khatib et al., 2008a and2008b). Importantly, SNP-SNP interactions between biologically interacting genes in the same signaling pathway were also found to contribute significantly to fertilization and early embryonic development (Khatib et al., 2009).Placental lactogen or chorionic soma...