The genetics of signal transduction and the feto-maternal relationship. A study of cytosolic low molecular weight phosphotyrosine phosphatase

Intracellular kinases mediate positive signalling ii-om surface receptors b y phosphorylating critical target proteins whereas phosphatases inhibit thi s process. Differential phosphatase activity at the fete-maternal interface could determine the appropriate relative growth and development on each si de of the placenta. The highly polymorphic cytosolic low molecular weight phosphotyrosine-phosp hatase (ACP1-cLMWPTPase) has been studied in 170 women who had at least two consecutive spontaneous abortions along with their husbands and in 352 nor mal puerperae along with their newborn babies. Symmetry analysis of joint wife/husband and mother/infant distribution sugg ests that when ACP1 activity is lower in the mother than in either her abor ted fetus or her child, the probability of abortion is higher and the survi val to term is lower as compared to pairs in which the ACP1 activity is hig her in the mother than in her fetus. Further analysis has shown that the ef fect is due to S isoform: i.e. a high mother/fetus Sisoform ratio favours i ntrauterine survival. Analysis of gestational duration and birth weight suggests that a high ACP1 maternal activity coupled with a low or moderate fetal activity favour fet al growth and developmental maturation. The present data indicate that maternal-fetal genetic differences in signal transduction could contribute significantly to variability of intrauterine developmental parameters manifestation of pregnancy.