In humans, studies of female germ cells are very limited by ethics. The cur
rent study investigated the usefulness of benign ovarian teratomas as a sub
stitute for ova in analyses of imprinted genes. Twenty-five human benign ov
arian teratomas were typed with 45 microsatellite DNA markers and classifie
d according to their genotypic features. Two oppositely imprinted genes, H1
9 and SNRPN, were then chosen for analysis of their methylation states in t
hese tumors. These analyses revealed that benign ovarian teratomas consist
of a mixture of genetically and epigenetically heterogeneous cell populatio
ns. In contrast to previous reports, we could document only one case rising
from germ cells by meiosis-II nondisjunction. H19 and SNRPN were methylate
d in individual teratomas to various degrees, ranging from normal somatic c
ell to expected ovum levels. The allele with residual methylation of H19 wa
s consistent with that methylated in the patient's blood DNA, thus being of
paternal origin. Degrees of H19 hypomethylation and SNRPN hypermethylation
increased as the cellular origin of the tumors advanced in oogenesis and w
ere closely correlated in individual teratomas. These results could be best
explained by the assumption that the primary imprinting is a progressively
organized process and suggest that the establishment of primary imprints o
n different genes might be mechanistically linked, even when those genes ar
e oppositely imprinted.