Neonatal Gastroenteritis Triggers Long-Term Cardiomyocyte Atrophy, Remodeling and Irreversible Hyperpolyploidization

Growth retardation, inflammation and cardiac overload in early childhood are linked with hypertension and infarction in adults. This link was termed as developmental programming. Exact mechanisms and critical time frames for development of the heart are still unknown. To elucidate these questions, we developed a model of moderate cryptosporidial gastroenteritis triggering main programming factors. Sliding the lime point of infection day by day (from day 4 to day 18), we tested complete rat neonatal period. Also, we repeated all experiments 30 days after infection. Using methods of cytometry, immunocytochemistry and confocal microscopy, we compared sensitivity of ventricular cardiomyocyte shape, protein content and ploidy. Our data indicated that gastroenteritis lasting four days triggered cardiomyocyte atrophy, almost doubling cell length to width ratio, and premature and excessive polyploidization. Surprisingly, nucleus and cytoplasm reacted to the disease differently. Cardiomyocytes accumulated genomes only when the disease covered the time period between 6 and 14 days after birth, when cells substitute proliferative growth with hypertrophy. Contractile proteins and cell shape on the contrary, showed high sensitivity in the course of complete neonatal period. After restoration, ploidy did not regress, whereas cell shape and protein content revealed moderate restoration. Taking into account that somatic polyploidy is irreversible and that it alters global gene expression pattern, we may suggest that genome duplication is one of the instruments of developmental programming and that gastroenteritis is one if the triggers of this programming.