During pregnancy the organism undergoes a variety of physiological changes affecting the cardiovascular system. The molecular mechanisms underlying these adaptations are poorly understood. Because of the recently developed concept of resident organotypic stem cells in the cardiovascular system, our aim is to explore the potential involvement of these cells and the related signaling cascades in this adaptation process. We have analyzed cell proliferation by immunostainings against pHH3/Ki67 and BrdU incorporation in mouse hearts at different stages during pregnancy. The different cardiac cell types, particularly cardiomyocytes (CMs), fibroblasts and endothelial cells (ECs) were identified by immunostainings. The average percentage of Ki67+ nuclei increased from virgin controls to gestational day 3 (G3), peaked at G14 and immediately stopped after delivery. Co-staining revealed that approximately 2/3 of the proliferating cells were fibroblasts and 1/3 ECs. The lack of CM proliferation was corroborated using BrdU pulse chase experiments, followed by Langendorff perfusion. Results were confirmed by flow cytometric analysis. The proliferation of fibroblasts and ECs appears to reflect angiogenesis and extracellular matrix remodeling known to occur during pregnancy induced hypertrophy. In accordance with these findings we detected CM hypertrophy and increased capillary density during pregnancy. Both parameters peaked postnatal but only CM hypertrophy decreased to virgin levels after lactation while capillary density remained elevated. To analyze the role of hormones in these physiological adaptive processes, plasma levels of progesterone, prolactin and estrogen were quantified. Progesterone- and prolactin- levels showed their maximal blood concentrations at G14 and declined at the day of delivery coinciding with the course of proliferation, whereas estrogen showed two distinct peaks at G3 and G18. We are currently investigating the mechanisms underlying pregnancy induced proliferation in cardiac ECs and fibroblasts.