Heme oxygenase/carbon monoxide system affects the placenta and preeclampsia

Vicki L. Mahan

¹Department of Surgery, Queen Elizabeth Central Hospital, Blantyre, Malawi²Drexel University Medical School, Philadelphia, PA, USA

Abstract

Preeclampsia affects 2% to 8% of pregnancies worldwide and results in significantly high maternal and perinatal morbidity and mortality, with delivery being the only definitive treatment. It is not a single disorder, but rather a manifestation of an insult(s) to the uteroplacental unit —whether maternal, fetal, and/or placental. Multiple etiologies have been implicated, including uteroplacental ischemia, maternal infection and/or inflammation, maternal obesity, sleep disorders, hydatidiform mole, maternal intestinal dysbiosis, autoimmune disorders, fetal diseases, breakdown of maternal-fetal immune tolerance, placental aging, and endocrine disorders. Early- and late-onset preeclampsia are associated with different etiologies: early-onset preeclampsia develops because of poor placentation, while late-onset preeclampsia occurs in women with latent maternal endothelial dysfunction. In preeclamptic placentas, acquired, genetic, and immune risk factors may result in impaired trophoblast invasion and spiral artery remodeling, which affects uteroplacental perfusion. The resulting placental hypoxia affects the heme oxygenase system—a known stress response pathway affected by hypoxia that is important during normal pregnancy and may offer a therapeutic approach in preeclampsia. This review will address the effect of the heme oxygenase/carbon monoxide system on the placenta and preeclampsia.

摘要：先兆子痫影响全世界2%至8%的妊娠，导致孕产妇和围产期发病率和死亡率极高，分娩是唯一确定的治疗方法。它不是一种单一的疾病，而是对子宫胎盘单位（无论是母体、胎儿还是胎盘）的侮辱的一种表现。涉及多种病因，包括子宫胎盘缺血、母体感染和/或炎症、母体肥胖、睡眠障碍、包虫痣、母体肠道生态失调、自身免疫性疾病、胎儿疾病、母胎免疫耐受破坏、胎盘老化和内分泌紊乱。早发性和晚发性先兆子痫与不同的病因相关：早发性先兆子痫的发生是因为胎盘不良，而晚发性先兆子痫发生在潜伏性母体内皮功能障碍的妇女。在子痫前期胎盘中，后天、遗传和免疫危险因素可导致滋养细胞侵袭和螺旋动脉重塑受损，从而影响子宫胎盘灌注。由此导致的胎盘缺氧影响血红素加氧酶系统，这是一种已知的受缺氧影响的应激反应途径，在正常妊娠期间是重要的，可能为子痫前期提供治疗方法。本文将讨论血红素加氧酶/一氧化碳系统对胎盘和子痫前期的影响。先兆子痫影响全世界2%至8%的妊娠，导致孕产妇和围产期发病率和死亡率极高，分娩是唯一确定的治疗方法。它不是一种单一的疾病，而是对子宫胎盘单位（无论是母体、胎儿还是胎盘）的侮辱的一种表现。涉及多种病因，包括子宫胎盘缺血、母体感染和/或炎症、母体肥胖、睡眠障碍、包虫痣、母体肠道生态失调、自身免疫性疾病、胎儿疾病、母胎免疫耐受破坏、胎盘老化和内分泌紊乱。早发性和晚发性先兆子痫与不同的病因相关：早发性先兆子痫的发生是因为胎盘不良，而晚发性先兆子痫发生在潜伏性母体内皮功能障碍的妇女。在子痫前期胎盘中，后天、遗传和免疫危险因素可导致滋养细胞侵袭和螺旋动脉重塑受损，从而影响子宫胎盘灌注。由此导致的胎盘缺氧影响血红素加氧酶系统，这是一种已知的受缺氧影响的应激反应途径，在正常妊娠期间是重要的，可能为子痫前期提供治疗方法。本文将讨论血红素加氧酶/一氧化碳系统对胎盘和子痫前期的影响。