Establishment of Canine Pregnancy – New Insights

Establishment and maintenance of pregnancy are the result of a balanced interaction of hormones, immune cells, paracrine and autocrine factores, and both the maternal and the fetal part contribute to the success. In the bitch, progesterone (P4) is essential for the establishment and maintenance of pregnancy (1). Progesterone has been found to promote the endometrial synthesis of the cytokine leukemia inhibitory factor (LIF; 2), which together with the presence of its receptor on the surface of trophoblast cells is considered to be important for trophoblast growth and differentiation, and for a shift towards the intrauterine predominance of T helper (Th) 2 cells (3). Recently we investigated the relative expression of P4 receptor (PR) and LIF in uterine tissues from early pregnant bitches by means of quantitative RT-PCR. Hypothesis was that a relation exists between the biological effect of P4 after its binding to the receptor and the uterine change in LIF expression, as has been described in primates. We assessed a significant decrease in the relative uterine expression of PR mRNA from day 10 (preimplantation) to day 30 (placentation, p<0.01). However, at the same time, the relative expression of LIF mRNA increased until placentation (p<0.05; own unpublished results). In addition, from the phase of embryo invasion until placentation, PR was no longer detectable in the fallopian tube. We therefore suppose, that LIF participates essentially in the establishment of canine pregnancy and that a direct or indirect effect of receptor bound P4 on the uterine expression of LIF exists. In addition, the effect of P4 on the intrauterine activity of enzymes as well as the paracrine secretion of cytokines and other factors has to be elucidated. In a former study we found, that before and during implantation, the average activity of matrixmetalloproteinase (MMP) -2 was significantly higher in serum of pregnant bitches than in serum of non-pregnant animals (4). [...]