Male microchimerism is frequent in the adult female liver and is attributed to fetal cells originating from previous male offspring. It has never been studied in pregnant women, female children, or fetuses. We examined its frequency and cellular nature in normal and diseased female livers from fetal life to adulthood. Forty-six liver samples from 29 women, 6 female children, and 11 female fetuses were screened for the Y chromosome via polymerase chain reaction (PCR) assay and fluorescent in situ hybridization (FISH). The X chromosome was used as an internal control. A third PCR assay was used for Y genotyping. The Y chromosome was detected in 5 of 6 children, 7 of 11 fetuses, 3 of 9 women with normal liver, 7 of 10 women with chronic hepatitis C, 5 of 6 women with acute liver disease during pregnancy with male offspring, and 2 of 4 nonpregnant women with fulminant hepatitis. In positive samples, the mean XY/XX ratio was 0.012 (؎0.004). In women, male microchimerism was correlated with previous male offspring. Male hepatocytes, detected via FISH combined with anti-hepatocyte immunohistochemistry, were observed only in fetuses (4/9) and in postpartem women (4/6). Y genotypes were different from each other in 4 of 5 female livers. In conclusion, male liver microchimerism is frequent in normal and diseased female livers. The presence of male cells in the liver of female children and fetuses is probably due to the transplacental transmission of fetal cells preexisting in the mother and acquired either from previous pregnancy with male offspring or during the mother's own fetal life.
(HEPATOLOGY 2005;42:35-43.) M ale cells have been detected in the liver in 30% to 70% of adult women by means of polymerase chain reaction (PCR)-based screening for the Y chromosome. The presence of male cells in adult female tissues is usually attributed to fetomaternal microchimerism originating from previous male offspring. Indeed, fetal cells are transfused into the maternal circulation during pregnancy and can persist in maternal blood and tissues for decades after delivery. However, male cells have not yet been studied in the liver of female children or fetuses in whom such fetomaternal transmission is impossible.
The biological significance of these cells is unknown, although they have been incriminated in the pathogenesis of autoimmune diseases such as systemic scleroderma, 10-14 Grave's disease, Hashimoto's thyroiditis, Goujerot-Sjo ¨gren syndrome, 17 and primary biliary cirrhosis. In addition, these fetal cells may give rise to stem cells, which may participate in the repair of damaged tissues, in the same way as bone marrow-derived cells of donor origin in marrow transplant recipients. A recent study based on fluorescent in situ hybridization (FISH) detection of the Y chromosome suggested that male fetal cells could differentiate into mature thyroid follicles in the damaged thyroid. Johnson et al., using the same method, recently suggested the existence of male hepatocytes in the liver of a woman with chronic viral hepatitis C. The possibility of male hepatocytes in the adult female liver was clearly shown by the same group by combining hepatocyte-specific staining and FISH.