Chromosome-substituted rat strains provide insights into the genetics of placentation

The rat possesses a hemochorial form of placentation. Pronounced intrauterine trophoblast cell invasion and vascular remodeling characterize this type of placentation. Strain-specific patterns of placentation are evident in the rat. Some rat strains exhibit deep intrauterine trophoblast invasion and an expanded junctional zone [Holtzman Sprague-Dawley (HSD), Dahl salt sensitive (DSS)], whereas placentation sites of other rat strains are characterized by shallow invasion and a restricted junctional zone [Brown Norway (BN)]. In this report, we identified a quantitative trait that was used to distinguish strain-specific features of rat placentation. Junctional zone prolactin family 5, subfamily a, member 1 (Prl5a1) transcript levels were significantly greater in BN rats than in HSD or DSS rats. Prl5a1 transcript levels were used as a quantitative trait to screen placentation sites from chromosome-substituted rat strains (BN chromosomes introgressed into the DSS inbred strain; DSS-BN panel). Litter size, placental weights, and fetal weights were not significantly different among the chromosome-substituted strains. Regulation of the junctional zone Prl5a1 transcript-level quantitative trait was multifactoral. Chromosome-substituted strains possessing BN chromosomes 14 or 17 introgressed into the DSS inbred rat strain displayed Prl5a1 transcript levels that were significantly different from the DSS pattern and more closely resembled the BN pattern. The in situ placental distribution of Prl5a1 mRNA and the structure of the junctional zone of DSS-BN17 rats mimicked that observed for the BN rat. Prl5a1 gene expression was also assessed in BN vs. HSD trophoblast stem cells and following reciprocal BN and HSD embryo transfer. Strain differences intrinsic to trophoblast and maternal environment were identified. In summary, we have identified chromosomes 14 and 17 as possessing regulatory information controlling a quantitative trait associated with rat placentation.