Prolificacy traits have been widely explored during the last decades as a potential tool for increasing efficiency of sow productivity in the pig industry. Genetic improvement programmes have achieved moderate gains in prolificacy related traits owing to their low heritability, late expression in life and sex limitation . Increasing knowledge on the genetic architecture of prolificacy traits would provide new tools to improve the efficiency of genetic selection by implementing marker assisted selection (MAS).
So far a relatively low number of quantitative trait loci (QTL) for prolificacy traits reaching the genome-wide significance level have been identified [2, 3]. The most significant QTL affecting the number of piglets born alive (NBA) and the total number of piglets born (TNB) were described by Noguera et al.  in the same resource population as used in the present study, an Iberian (Ib) by Meishan (Me) F2 intercross. A number of epistatic QTL were also detected, thus indicating that the genetic architecture of reproductive traits is built as a complex network of interactions throughout the genome. Some of these epistatic QTL were further confirmed and putative candidate interacting genes were identified .
Porcine chromosome 13 (SSC13) harbours the most significant QTL for TNB and NBA . The Mucin 4 (MUC4) gene is located within the confidence interval of prolificacy QTL. Mucins are large heterodimeric glycoproteins commonly located on apical surfaces of many wet-surfaced epithelia that play a key role in the lubrication and protection of the uterine mucosa [5–7]. They have been shown to present anti-adhesive and anti-recognition properties which are necessary to protect the endometrium from the binding and invasion of the trophoectoderm [8, 9]. A role of MUC4 has been pointed out in rodents and pigs during pregnancy although its expression during the peri-implantational period varies depending on the type of implantation in each species. In mice and rats, which have an invasive type of implantation, MUC4 expression is downregulated to generate the receptive state for uterine implantation [8–12]. Conversely, in pigs, where a non-invasive epitheliochorial placental attachment takes place, MUC4 is upregulated in the uterus . A protective role has been suggested for MUC4 owing to the fact that it is localized on the endometrium epithelium blocking the access of different substrates to the cell surface . The endometrium is then protected from proteolytic activity of porcine conceptus  and from microbial invasion  resulting in better uterine conditions for embryo development. In pigs, the disruption of the uterine microenvironment could affect embryo viability which could lead to prenatal mortality rates ranging from 20 to 46% . The improvement of the uterine microenvironment would increase embryonic survival and, in consequence, the number of piglets born alive.
In humans, polymorphisms in the MUC4 nucleotide sequence have been significantly associated with the development of endometriosis and endometriosis related infertility . However, no association with implantation failure has been detected . In livestock species, the genetic association of MUC4 gene variants with reproductive traits has not yet been explored. In pigs, polymorphisms in the MUC4 gene were shown to be in linkage disequilibrium with susceptibility/resistance to Enterotoxigenic Escherichia
coli (ETEC) F4ab/ac infection .
In the current study, we have examined the porcine MUC4 gene as a functional and positional candidate gene to explain the prolificacy QTL previously identified on SSC13 in the Ib × Me population .