ALTERATIONS OF HUMAN PLACENTAL EPIDERMAL GROWTH-FACTOR RECEPTOR IN INTRAUTERINE GROWTH-RETARDATION

We studied human placental microvillous EGF receptor (EGFR) and its re lationship with maternal and placental features in 14 cases of intraut erine growth retardation. Placental EGFR phosphorylation was significa ntly decreased or absent in 12 cases of small for gestational age neon ates, as shown by SDS-PAGE, autoradiography, and scanning analysis. Sp ecific [I-125]EGF binding and Scatchard plots of the binding data show ed a decreased number of EGFR in 6 of the 12 cases, with a mean maxima l binding capacity of 1.09 +/- 0.32 pmol/mg for high affinity sites (m ean control value = 2.30 +/- 0.23 pmol/mg). Most of the hypertensive w omen and smokers belonged to this subgroup. In three of the remaining six cases of small gestational age placentas with low EGFR phosphoryla tion, there was no maternal pathology or significant parenchymatous pl acental lesions. Five showed a 175-kD EGFR species when probed by [I-1 25]EGF cross-linking and Western blotting with RK2 and C-Term, two pol yclonal anti-EGFR antibodies, suggesting abnormal transduction of the EGF-induced signal. The sixth placenta yielded a single 145-kD EGFR ba nd consistent with an abnormal EGFR structure; Western blot analysis s howed no immunoreactive band. In conclusion, maternal and placental pa thologies in intrauterine growth retardation are associated with vario us alterations of placental EGFR, pointing out the importance of EGFR ligands in the regulatory pathway of placental anf fetal growth.