Spiral artery remodeling in preeclampsia revisited.

T he first observations that placental bed defects were potentially linked to clinical outcomes such as pre-eclampsia (PE) were made nearly 50 years ago. 1 This study followed prior findings that the placental clearance of radio-labeled saline was significantly decreased in women with hypertensive gestations. 2 Histological examination of pla-centas and placental bed biopsies obtained from complicated gestations and compared with normotensive controls were performed in hopes to discern histopathologic causes for clinical outcomes. Decades of research into placental histo-pathology have held fast to certain dogma; defects in spiral artery remodeling and trophoblast invasion are characteristic of hypertensive disorders of pregnancy and fetal growth restriction (FGR). These 2 processes, deemed essential for normal pregnancy, are mechanistically not understood. Our current understanding of spiral artery remodeling and tropho-blast invasion is that they are highly interrelated , but separate processes. Regulation is likely multifactorial, including genetic, immune, maternal, fetal, endocrine, and cardiovascu-lar influences. Temporal regulation is known, making timing of study and sampling a large issue, particularly in women. Typically, samples are only available as terminations in first trimester, before presentation of maternal disease, or at term, well after disease presentation. There is no opportunity for serial sampling, which is an understandable limitation, to our current knowledge, in humans. Data from animal models have yielded important findings, although the potential for translation to humans is questionable. Even in studies of animals with hemochorial placentation, several differences are apparent. Perhaps the best studied are mice, with short (19–20) day gestations and significant decidual spiral artery remodeling. In mice, specialized terminally differentiated lymphocytes called uterine natural killer cells are primarily responsible for arterial remodeling in this species. Trophoblastic invasion in mice is relatively shallow and is temporally restricted to late gestation, generally considered a minor contributor to arterial remodeling. In rats, invasion of trophoblast is more robust, extending deep into the myometrium in normal gestations. In a rat model of PE, trophoblast invasion was observed to be more extensive than control gestations at term. 7 Mice with impaired spiral artery remodeling remained normotensive throughout gestation without development of proteinuria or fetal growth restriction. 8 The range of genetically manipulated rodents available for study has undoubtedly broadened our knowledge; however, whether impaired spiral artery remodel-ing is the cause or consequence of the complicated pregnancy is still unclear. Thus, to gain better understanding of human complications of pregnancy, we require more careful study of humans. Currently, …