Identification of Male Cardiomyocytes of Extracardiac Origin in the Hearts of Women with Male Progeny: Male Fetal Cell Microchimerism of the Heart

Abstract

Fetal progenitor cells may cross the placenta during pregnancy, persist for decades in the maternal bloodstream, and find a microenvironment conducive to colonization in a variety of maternal solid organs. Whether extracardiac fetal progenitors are present in the heart of women with male issue is unknown. The hearts from 2 non-pregnant women who had given birth to 2 and 3 male children, respectively, were studied. Myocardial specimens from 2 men and 2 women (without history of pregnancies) were used as controls. Real time polymerase chain reaction was performed to amplify the SRY gene located at the Y chromosome. Fluorescence in situ hybridization (FISH) with probes specific for X and Y chromosomes was combined with alpha-actin immunohistochemistry to identify cardiac muscle cells. Histocompatibility studies were conducted in both patients and their male relatives. The SRY gene was amplified in the myocardium of both patients. FISH analysis showed clear evidence of male cells with the typical cardiomyocyte phenotype within the myocardium. X- and Y-chromosome bodies in the nuclei were found in 0.25% and 0.20% of cells, respectively. Increased human leukocyte antigen compatibility was observed between patients and their sons. This study identified male cardiomyocytes of extracardiac origin, presumably fetal, in the hearts of 2 women with male progeny. Fetal progenitor cells may colonize the heart and under appropriate microenvironmental stimuli, differentiate into cardiomyocytes.