The unique endometrial expression and genomic organization of the porcine IGFBP-2 gene

The insulin-like growth factor-binding proteins (IGFBPs-1-6) modulate the mitogenic and differentiative actions of the IGFs and may have IGF-independent functions, This study examined the gene expression and pregnancy-regulation of the IGF/IGFBP system in porcine uterine endometrium and myometrium during the periimplantation period and later stages of pregnancy. Endometrial IGFBP-2 mRNA abundance exhibited stage of pregnancy-dependent induction; whereas little or no IGFBP-2 mRNA was found in myometrium. IGFBP-2 protein was immunolocalized to the endometrial glandular and luminal epithelia (staining on day 60 > day 12) with minimal or no immunostaining of uterine stroma observed. IGFBP-3 and IGFBP-4 transcript levels became elevated in endometrium after implantation; whereas, IGFBP-5 and IGFBP-6 mRNAs were in greater abundance in periimplantation than post-implantation endometrium. IGFBP-1 transcripts, in contrast, could not be identified in porcine endometrium or myometrium of pregnancy. As a pre-requisite to understanding the pregnancy-induction and endometrial-specificity of the uterine-expressed IGFBP-2 gene, cosmids encompassing the pig IGFBP-2 chromosomal locus were isolated and characterized. This gene is comprised of four exons that span > 29 kb and encode a 316 amino acid precursor protein, All four exons were found to be G/C rich with exon 1 and immediate 5' flank exhibiting hallmarks of a CpG island. This latter region was devoid of TATA and CAAT motifs. Results identify the preferential endometrial expression of different IGFBP genes at either the periimplantation or post-implantation periods, perhaps reflecting distinct actions of these proteins at the embryo-maternal and feto-maternal interfaces, respectively. Interactions of steroid receptors, endometrial transcription factors and their corresponding cis elements may confer the unique uterine expression of the IGFBP-2 gene.