Vessel remodelling, pregnancy hormones and extravillous trophoblast function.

During early human pregnancy, extravillous trophoblast (EVT) cells from the placenta invade the uterine decidual spiral arterioles and mediate the remodelling of these vessels such that a low pressure, high blood flow can be supplied to the placenta. This is essential to facilitate normal growth and development of the foetus. Defects in remodelling can manifest as the serious pregnancy complication pre-eclampsia. During the period of vessel remodelling three key pregnancy-associated hormones, human chorionic gonadotrophin (hCG), progesterone (P(4)) and oestradiol (E(2)), are found in high concentrations at the maternal-foetal interface. Potentially these hormones may control EVT movement and thus act as regulators of vessel remodelling. This review will discuss what is known about how these hormones affect EVT proliferation, migration and invasion during vascular remodelling and the potential relationship between hCG, P(4), E(2) and the development of pre-eclampsia.

The effects of human chorionic gonadotrophin, progesterone and oestradiol on trophoblast function.

Remodelling of the uterine vasculature during the first trimester of human pregnancy requires invasion of trophoblast from the placenta into decidual spiral arterioles. The pregnancy-associated hormones human chorionic gonadotropin (hCG), progesterone (P(4)) and oestradiol (E(2)) are present at high concentrations at the maternal-fetal interface during the remodelling period and thus may contribute to the regulation of trophoblast movement. This study examined the effects of these hormones on trophoblast functions. HTR8/SVneo cells were treated with hCG (5-100mIU/mL), P(4) (20nM-20µM) or E(2) (0.07-734nM). hCG significantly stimulated migration and MMP-9 activity but did not affect cell numbers. P(4) significantly inhibited migration, MMP-2 and -9 activity and reduced cell numbers. E(2) had no effect on migration, MMP activity or cell numbers. We conclude that hCG and P(4), but not E(2), play direct roles in controlling trophoblast invasion, acting as positive and negative stimuli respectively to regulate trophoblast movement during vascular remodelling in early pregnancy.