Departments of Physiology and Functional Genomics, and of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville, FL 32610, United States.
Department of Animal Reproduction, Universidad Nacional de Rio Cuarto, Rio Cuarto, Cordoba, Argentina.
Placenta. 2017 Dec;60:119-129. doi: 10.1016/j.placenta.2017.06.005. Epub 2017 Jun 9.
In normal human placentation, uterine invasion by trophoblast cells and subsequent spiral artery remodeling depend on cooperation among fetal trophoblasts and maternal decidual, myometrial, immune and vascular cells in the uterine wall. Therefore, aberrant function of anyone or several of these cell-types could theoretically impair placentation leading to the development of preeclampsia. Because trophoblast invasion and spiral artery remodeling occur during the first half of pregnancy, the molecular pathology of fetal placental and maternal decidual tissues following delivery may not be informative about the genesis of impaired placentation, which transpired months earlier. Therefore, in this review, we focus on the emerging prospective evidence supporting the concept that deficient or defective endometrial maturation in the late secretory phase and during early pregnancy, i.e., pre-decidualization and decidualization, respectively, may contribute to the genesis of preeclampsia. The first prospectively-acquired data directly supporting this concept were unexpectedly revealed in transcriptomic analyses of chorionic villous samples (CVS) obtained during the first trimester of women who developed preeclampsia 5 months later. Additional supportive evidence arose from investigations of Natural Killer cells in first trimester decidua from elective terminations of women with high resistance uterine artery indices, a surrogate for deficient trophoblast invasion. Last, circulating insulin growth factor binding protein-1, which is secreted by decidual stromal cells was decreased during early pregnancy in women who developed preeclampsia. We conclude this review by making recommendations for further prospectively-designed studies to corroborate the concept of endometrial antecedents of preeclampsia. These studies could also enable identification of women at increased risk for developing preeclampsia, unveil the molecular mechanisms of deficient or defective (pre)decidualization, and lead to preventative strategies designed to improve (pre)decidualization, thereby reducing risk for preeclampsia development.
在正常的人类胎盘形成过程中，滋养细胞向子宫侵袭和随后的螺旋动脉重塑依赖于胎儿滋养细胞与母体蜕膜、子宫肌层、免疫和血管细胞在子宫壁中的合作。因此，这些细胞类型中的任何一种或几种的功能异常都可能理论上损害胎盘形成，导致子痫前期的发生。由于滋养细胞侵袭和螺旋动脉重塑发生在妊娠的前半段，因此分娩后胎儿胎盘和母体蜕膜组织的分子病理学可能不能说明数月前发生的胎盘形成受损的发生机制。因此，在这篇综述中，我们重点介绍了支持以下概念的新兴前瞻性证据，即晚期分泌期和早期妊娠（即前蜕膜化和蜕膜化）中子宫内膜成熟不足或缺陷可能导致子痫前期的发生。第一个直接支持这一概念的前瞻性获得的数据是在妊娠 5 个月后发生子痫前期的女性的妊娠早期绒毛膜绒毛样本（CVS）的转录组分析中意外发现的。从对具有高阻力子宫动脉指数的女性的妊娠早期蜕膜中的自然杀伤细胞的研究中获得了额外的支持证据，高阻力子宫动脉指数是滋养细胞侵袭不足的替代指标。最后，在发生子痫前期的女性中，在妊娠早期循环中的胰岛素生长因子结合蛋白-1（由蜕膜基质细胞分泌）减少。我们通过提出进一步前瞻性设计研究的建议来结束这篇综述，以证实子痫前期的子宫内膜前体的概念。这些研究还可以识别出发生子痫前期风险增加的女性，揭示出（前）蜕膜化不足或缺陷的分子机制，并导致旨在改善（前）蜕膜化、从而降低子痫前期发生风险的预防策略。
