O'Hern Perfetto Candice, Fan Xiujun, Dahl Sabita, Krieg Sacha, Westphal Lynn Marie, Bunker Lathi Ruth, Nayak Nihar R
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Stanford University Medical Center, 900 Welch Rd, Suite 20, Palo Alto, CA, 94304, USA,
J Assist Reprod Genet. 2015 Jun;32(6):977-84. doi: 10.1007/s10815-015-0481-7. Epub 2015 May 1.
Researchers have hypothesized that an imbalance of immune cells in the uterine decidua and a dysfunction in cytokines they produce may contribute to recurrent pregnancy loss (RPL). The objective of this study was to determine if IL-22, IL-23 and IL-17 are expressed abnormally in the decidua of patients with RPL compared to those women with a normal pregnancy. We also sought to confirm that uterine natural killer (uNK) cells are lower in the decidua of patients with RPL, as well as identify IL-22 expression by uNK cells.
After meeting strict inclusion criteria, maternal decidua of nine patients with unexplained RPL and a confirmed euploid fetal loss, and 11 gestational age-matched patients undergoing elective pregnancy termination were included in our analysis. Quantitative real time-polymerase chain reaction (qRT-PCR) was performed to quantify RNA expression, Western blot was performed to quantify protein expression and immunohistochemistry (IHC) was performed to identify IL-22 and uNK cells.
We found that women with unexplained RPL and a euploid fetal loss had significantly less gene and protein expression of IL-22 in the decidua. Additionally, we found that IL-22 is primarily expressed by uNK cells in the decidua.
In conclusion, our results suggest that lower levels of IL-22 in the uterine decidua in patients with unexplained RPL may contribute to a disruption of decidual homeostasis and ultimately lead to early pregnancy loss.
研究人员推测,子宫蜕膜中免疫细胞失衡及其产生的细胞因子功能障碍可能导致复发性流产(RPL)。本研究的目的是确定与正常妊娠女性相比,RPL患者蜕膜中白细胞介素-22(IL-22)、白细胞介素-23(IL-23)和白细胞介素-17(IL-17)的表达是否异常。我们还试图证实RPL患者蜕膜中的子宫自然杀伤(uNK)细胞数量较少,并确定uNK细胞中IL-22的表达情况。
在满足严格的纳入标准后,我们分析纳入了9例原因不明的RPL且确诊为整倍体胎儿丢失患者的母体蜕膜,以及11例孕龄匹配的接受选择性妊娠终止的患者。采用定量实时聚合酶链反应(qRT-PCR)定量RNA表达,采用蛋白质免疫印迹法定量蛋白质表达,并采用免疫组织化学(IHC)鉴定IL-22和uNK细胞。
我们发现,原因不明的RPL且整倍体胎儿丢失的女性蜕膜中IL-22的基因和蛋白质表达显著降低。此外,我们发现IL-22主要由蜕膜中的uNK细胞表达。
总之,我们的结果表明,原因不明的RPL患者子宫蜕膜中IL-22水平较低可能导致蜕膜内环境稳态破坏,最终导致早期妊娠丢失。