TIMP-1 as candidate gene for embryo survival in two divergent lines selected for uterine capacity in rabbits

Selection on uterine capacity has been used in animal breeding as a way to improve the litter size. A divergent selection experiment for uterine capacity was performed in rabbits during ten generations. After the first generations of selection, large differences in number of implanted embryos were obtained between high and low lines. The major part of the differences between lines was due to embryo survival. A segregation analysis suggested the presence of a major gene affecting the reproductive traits. The objective of this work was to test the TIMP-1 gene as a candidate gene for embryo survival in rabbits since it stands up as a target for the investigation of reproductive problems in humans. We have analyzed the parental generation of a F2 cross which consists of 8 and 14 animals from the high and low uterine capacity lines, respectively. The rabbit TIMP-1 gene structure and sequence has been determined, including the proximal promoter region. Despite of the absence of polymorphism between lines in the screened regions (CDS, proximal promoter, exon 1, intron 1, and exon 2), a real-time RT-PCR quantification of the TIMP-1 mRNA in oviduct has shown significant differences between high and low lines at 62 hr of gestation, just when rabbit embryos are located in the oviduct, postulating TIMP-1 as an interesting candidate gene to be involved in the phenotypic differences between the two rabbit lines.