The possible role of prolactin in preeclampsia: 2001, a hypothesis revisited a quarter of century later

Abstract 

A genetic predisposition (theory 1) to preeclampsia in a woman with or without risk factors, may lead to an immune maladaptation to pregnancy (theory 2) (Th1 type of immune response predominance over Th2). In turn, they may contribute to an early defective `switch' (quantitatively or out of timing) with a predominant decidual production of 16-kDa PRL over that of a 23-kDa PRL (our hypothesis), which induces an antiangiogenic process with a shallow invasion of the spiral arteries by the endovascular cytotrophoblast. Afterwards, a high-resistance arteriolar system and placental ischemia or hypoxia ensue, leading to endothelial cell dysfunction (theory 3) and an increased oxidative stress (theory 4). We are not proposing any strict chronological sequence of events, but the early occurrence (first 10 weeks) during pregnancy of the predominant decidual secretion of a 16-kDa PRL over that of 23-kDa PRL inducing a defective angiogenic process. No other specific mechanism(s) to explain the `shallow' invasion of the spiral arteries has been previously proposed. Furthermore, it seems to happen early enough in pregnancy, as a `very early change which may give a clue to the etiology,' as first suggested 25 years ago by Horrobin.