Endocrine Abstracts

During early development, the extravillous and villous placenta form by a process of proliferation and differentiation resulting in invasion of the uterine decidua and myometrium. The invasion of tissues during placentation is a model for the proliferative and invasive processes which occur during tumourogenesis. Pituitary tumor transforming gene (PTTG) interacts with a binding factor PBF, and PTTG expression correlates with tumor invasiveness in many neoplasms. We hypothesised that the invasive processes which occur during placentation may be related to PTTG and PBF expression and that their expression profile may be altered in malplacentation syndromes which are associated with reduced trophoblast invasion. We therefore examined the expression of these genes in placentae from normal pregnancies and those affected by intrauterine growth restriction (IUGR). PTTG mRNA expression increased with advancing gestational age reaching a peak at 13-20 weeks (13-fold increase compared with 6-8 weeks cohort, p=0.001), whereas PBF mRNA decreased through gestation reaching a nadir at 27-34 weeks (64% reduction compared with 6-8 weeks, p=0.001). Markedly increased PTTG mRNA levels were detected in both early (7.3-fold increase compared with gestation matched normal samples, p<0.001) and late (3.9-fold increase, p=0.017) IUGR-affected pregnancies. Similarly, PBF expression was increased in both early (7.9-fold, p<0.01) and late IUGR (5.1-fold, p<0.01). Western blotting of normal placentae confirmed the presence of PTTG protein in normal and IUGR affected placentae from the first trimester onwards. Immunohistochemical analysis demonstrated marked cytoplasmic and nuclear staining in the syncytio- and cytotrophoblast of villous placenta, with little immunostaining of the villous stroma.

Conclusion: We propose that PTTG and its binding factor PBF may play a role in influencing proliferation and migration of the trophoblast, processes which are abnormal in malplacentation syndromes, such as IUGR.