NORMAL AND ATYPICAL BUTYRYLCHOLINESTERASES IN PLACENTAL DEVELOPMENT, FUNCTION, AND MALFUNCTION

1. In utero exposure to poisons and drugs (e.g., anticholinesterases, cocaine) is frequently associated with spontaneous abortion and placen tal malfunction. The major protein interacting with these compounds is butyrylcholinesterase (BuChE), which attenuates the effects of such x enobiotics by their hydrolysis or sequestration. Therefore, we studied BuChE expression during placental development. 2. RT-PCR revealed bot h BuChEmRNA and acetylcholinesterase (AChE) mRNA throughout gestation. However, cytochemical staining detected primarily BuChE activity in f irst-trimester placenta but AChE activity in term placenta. 3. As the atypical variant of BuChE has a narrower specificity for substrates an d inhibitors than the normal enzyme, we investigated its interactions with alpha-solanine and cocaine, and sought a correlation between the occurrence of this variant and placental malfunction. 4. Atypical BuCh E of serum or recombinant origin presented >10-fold weaker affinities than normal BuChE for cocaine and alpha-solanine. However, BuChE in th e serum of a heterozygote and a homozygous normal were similar in thei r drug affinities. Therefore, heterozygous serum or placenta can prote ct the fetus from drug or poison exposure, unlike homozygous atypical serum or placenta. 5. Genotype analyses revealed that heterozygous car riers of atypical BuChE were threefold less frequent among 49 patients with placental malfunction than among 76 controls or the entire Israe li population. These observations exclude heterozygote carriers of aty pical BuChE from being at high risk for placental malfunction under ex posure to anticholinesterases.