Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States.
Department of Pediatrics Division of Neonatology, University of Rochester School of Medicine, Rochester, NY, United States.
J Nutr. 2023 Jul;153(7):1950-1958. doi: 10.1016/j.tjnut.2023.05.023. Epub 2023 May 28.
The iron regulatory hormones erythroferrone (ERFE), erythropoietin (EPO), and hepcidin, and the cargo receptor nuclear receptor coactivator 4 (NCOA4) are expressed in the placenta. However, determinants of placental expression of these proteins and their associations with maternal or neonatal iron status are unknown.
To characterize expression of placental ERFE, EPO, and NCOA4 mRNA in placentae from newborns at increased risk of iron deficiency and to evaluate these in relation to maternal and neonatal iron status and regulatory hormones.
Placentae were collected from 114 neonates born to adolescents carrying singletons (14-18 y) and 110 neonates born to 54 adults (20-46 y) carrying multiples. Placental EPO, ERFE, and NCOA4 mRNA expression were measured by RT-qPCR and compared with maternal and neonatal iron status indicators (SF, sTfR, total body iron, serum iron) and hormones.
Placental ERFE, EPO, and NCOA4 mRNA were detected in all placentae delivered between 25 and 42 wk of gestation. Relationships between placental ERFE and EPO differed by cohort. In the multiples cohort, placental EPO and ERFE were positively correlated (P = 0.004), but only a positive trend (P = 0.08) was evident in the adolescents. Placental EPO and ERFE were not associated with maternal or neonatal iron status markers or hormones in either cohort. Placental NCOA4 was not associated with placental EPO or ERFE in either cohort but was negatively associated with maternal SF (P = 0.03) in the multiples cohort and positively associated with neonatal sTfR (P = 0.009) in the adolescents.
The human placenta expresses ERFE, EPO, and NCOA4 mRNA as early as 25 wk of gestation. Placental expression of ERFE and EPO transcripts was not associated with maternal or neonatal iron status. Greater placental NCOA4 transcript expression was evident in women and newborns with poor iron status (lower SF and higher sTfR, respectively). Further research is needed to characterize the roles of these proteins in the human placenta.
These clinical trials were registered at clinicaltrials.gov as NCT01019902 (https://clinicaltrials.gov/ct2/show/NCT01019902) and NCT01582802 (https://clinicaltrials.gov/ct2/show/NCT01582802).
铁调节激素红细胞生成素(EPO)、铁调素和核受体共激活因子 4(NCOA4)在胎盘中有表达。然而,这些蛋白质在胎盘表达的决定因素及其与母体或新生儿铁状态的关系尚不清楚。
描述铁缺乏风险增加的新生儿胎盘中红细胞生成素(EPO)、Erythroferrone(ERFE)和 NCOA4mRNA 的表达,并评估其与母体和新生儿铁状态及调节激素的关系。
从 114 名青少年(14-18 岁)单胎妊娠和 110 名 54 名成年(20-46 岁)多胎妊娠的新生儿中采集胎盘。采用 RT-qPCR 法测定胎盘 EPO、ERFE 和 NCOA4mRNA 的表达,并与母体和新生儿铁状态指标(SF、sTfR、总铁量、血清铁)和激素进行比较。
在 25 至 42 周妊娠期间分娩的所有胎盘中均检测到胎盘 ERFE、EPO 和 NCOA4mRNA。EPO 和 ERFE 与胎盘的关系因队列而异。在多胎妊娠队列中,胎盘 EPO 和 ERFE 呈正相关(P=0.004),但在青少年中仅呈正趋势(P=0.08)。在两个队列中,胎盘 EPO 和 ERFE 均与母体或新生儿铁状态标志物或激素无关。在两个队列中,胎盘 NCOA4 与胎盘 EPO 或 ERFE 均无相关性,但与多胎妊娠队列中母体 SF(P=0.03)呈负相关,与青少年中新生儿 sTfR(P=0.009)呈正相关。
人类胎盘早在 25 周妊娠时就表达 ERFE、EPO 和 NCOA4mRNA。ERFE 和 EPO 转录本在胎盘中的表达与母体或新生儿的铁状态无关。在铁状态较差(SF 较低,sTfR 较高)的妇女和新生儿中,胎盘 NCOA4 转录本的表达更为明显。需要进一步研究这些蛋白质在人类胎盘中的作用。
这些临床试验在 clinicaltrials.gov 上注册为 NCT01019902(https://clinicaltrials.gov/ct2/show/NCT01019902)和 NCT01582802(https://clinicaltrials.gov/ct2/show/NCT01582802)。