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

Abstract

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.

Candidate gene analysis for reproductive traits in two lines of rabbits divergently selected for uterine capacity1

“…In addition, a complex segregation analysis performed by Argente et al (2003) found evidence of major genes with a moderate effect on UC and a large effect on embryo survival and number of implanted embryos in these rabbit lines. Moreover, Estellé et al (2006) reported a greater expression of TIMP1 in the High line. This gene is expressed in the oviduct at 62 h of gestation.…”

La génomique du lapin : avancées, applications et perspectives

“…Les études de gènes candidats pour les caractères de reproduction sont toutes fondées sur une seule population expérimentale sélectionnée de façon divergente pour la capacité uté-rine (nombre maximal de foetus qu'une lapine peut porter lorsque le taux d'ovulation n'est pas facteur limitant) pendant 10 générations (Mocé et al, 2004). Une association entre le polymorphisme de trois gènes (OVGP1, PGR et TIMP1) et quelques caractères de reproduction, incluant l'implantation embryonnaire et la taille de portée, a été mise en évidence dans cette population expérimentale (Estellé et al, 2006 ;Peiró et al, 2008 ;Peiró et al, 2010 ;Argente et al, 2010 ;García et al, 2010).…”

Genome Mapping and Genomics in Domestic Animals

“…A divergent selection experiment for uterine capacity has been carried out, and results suggest the presence of a major gene affecting uterine capacity and a correlated trait, which is the number of implanted embryos (Argente et al 2003). Progesterone receptor (PRG) , oviductin , and tissue inhibitor of matrix metalloproteinase-1 (TIMP1) (Estellé et al 2006) have been studied as candidate genes. SNPs within the PRG promoter and exon 11 of oviductin identified previously (Merchan et al 2005) were tested.…”