The genetics of signal transduction and the feto-maternal relationship. A study of cytosolic low molecular weight phosphotyrosine phosphatase.
Intracellular kinases mediate positive signalling from surface receptors by phosphorylating critical target proteins whereas phosphatases inhibit this process. Differential phosphatase activity at the feto-maternal interface could determine the appropriate relative growth and development on each side of the placenta. The highly polymorphic cytosolic low molecular weight phosphotyrosine-phosphatase (ACP1-cLMWPTPase) has been studied in 170 women who had at least two consecutive spontaneous abortions along with their husbands and in 352 normal puerperae along with their newborn babies. Symmetry analysis of joint wife/husband and mother/infant distribution suggests that when ACP1 activity is lower in the mother than in either her aborted fetus or her child, the probability of abortion is higher and the survival to term is lower as compared to pairs in which the ACP1 activity is higher in the mother than in her fetus. Further analysis has shown that the effect is due to S isoform: i.e. a high mother/fetus S isoform ratio favours intrauterine survival. Analysis of gestational duration and birth weight suggests that a high ACP1 maternal activity coupled with a low or moderate fetal activity favour fetal 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 and to pathological manifestation of pregnancy.
Bottini
E
E
Chair of Preventive and Social Pediatrics, University of Rome Tor Vergata, School of Medicine, Italy. bottini@med.uniroma2.it
Cosmi
E
E
Nicotra
M
M
Santeusanio
G
G
La Torre
M
M
Bottini
N
N
Lucarini
N
N
D000026:Abortion, Habitual / Q000235:genetics*; D000022:Abortion, Spontaneous / Q000235:genetics*; D003600:Cytosol; D005314:Embryonic and Fetal Development; D004789:Enzyme Activation; D005260:Female; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D008970:Molecular Weight; D011247:Pregnancy; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D015398:Signal Transduction / Q000235:genetics
D007527:Isoenzymes; D011518:Proto-Oncogene Proteins; C490429:ACP1 protein, human; D017027:Protein Tyrosine Phosphatases