Choo Sung Pil, Lee Inha, Lee Jae-Hoon, Lee Dowon, Park Hyemin, Park Joo Hyun, Cho SiHyun, Choi Young Sik
Department of Obstetrics and Gynecology, Inha University Hospital, College of Medicine, Inha University, Incheon, Korea.
Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Obstet Gynecol Sci. 2023 Sep;66(5):417-429. doi: 10.5468/ogs.22315. Epub 2023 Jul 17.
This study aimed to evaluate the endometrial transcriptomic patterns in the early secretory phase (ESP) and mid-secretory phase (MSP) of the natural menstrual cycle before in vitro fertilization and embryo transfer (IVF-ET).
Thirty patients whose endometrial tissues were obtained from the ESP or MSP of a natural menstrual cycle immediately before IVF-ET were included. Endometrial dating was histologically confirmed as ESP (cycle days 16-18) or MSP (cycle days 19-21), according to the noyes criteria. The patients were divided into two groups depending on the IVF-ET outcome: pregnant (n=14; 7 in ESP and 7 in MSP) or non-pregnant (n=16; 8 in ESP and 8 in MSP). Differentially expressed genes (DEGs) in the MSP, compared to the ESP, were identified using NanoString nCounter (NanoString Technologies, Seattle, WA, USA) data for both the pregnant and non-pregnant groups.
Thirteen DEGs in the pregnant group and 11 DEGs in the non-pregnant group were identified in the MSP compared to those in the ESP. In both groups, adrenoceptor alpha 2A, interleukin 1 receptor-associated kinase 2, a disintegrin and metalloproteinase with thrombospondin repeats 15 (ADAMTS15), serpin family E member 1, integrin subunit beta 3, transmembrane protein 252 (TMEM252), huntingtin associated protein 1, C2 calcium-dependent domain containing 4A, and integrin subunit alpha 2 were upregulated in the MSP, compared to the ESP. TMEM37, galactosidase beta 1 like 2, Rho family GTPase 3, and cytochrome P450 family 24 subfamily A member 1 were upregulated in the MSP only in the pregnant group. ADAMTS8 was downregulated and monoamine oxidase A was upregulated in the MSP only in the non-pregnant group.
Transcriptomic patterns in the endometrium immediately before IVF-ET appear to differ according to the IVF-ET outcome. These novel DEGs, which have not been previously studied, may have functional significance during the window of implantation and serve as potential biomarkers of endometrial receptivity.
本研究旨在评估体外受精与胚胎移植(IVF-ET)前自然月经周期中分泌期早期(ESP)和分泌期中段(MSP)的子宫内膜转录组模式。
纳入30例患者,其子宫内膜组织取自IVF-ET前自然月经周期的ESP或MSP。根据诺伊斯标准,经组织学确认子宫内膜处于ESP(月经周期第16 - 18天)或MSP(月经周期第19 - 21天)。根据IVF-ET结果将患者分为两组:妊娠组(n = 14;ESP组7例,MSP组7例)和非妊娠组(n = 16;ESP组8例,MSP组8例)。利用NanoString nCounter(美国华盛顿州西雅图市的NanoString Technologies公司)的数据,确定妊娠组和非妊娠组中与ESP相比,MSP中差异表达基因(DEG)。
与ESP相比,妊娠组在MSP中鉴定出13个DEG,非妊娠组在MSP中鉴定出11个DEG。在两组中,与ESP相比,MSP中肾上腺素能受体α2A、白细胞介素1受体相关激酶2、含血小板反应蛋白基序的解聚素和金属蛋白酶15(ADAMTS15)、丝氨酸蛋白酶抑制剂家族E成员1、整合素亚基β3、跨膜蛋白252(TMEM252)、亨廷顿蛋白相关蛋白1、含C2钙依赖性结构域4A和整合素亚基α2均上调。仅在妊娠组中,MSP中TMEM37、β1类半乳糖苷酶2、Rho家族GTP酶3和细胞色素P450家族24亚家族A成员1上调。仅在非妊娠组中,MSP中ADAMTS8下调,单胺氧化酶A上调。
IVF-ET前子宫内膜的转录组模式似乎因IVF-ET结果而异。这些以前未被研究过的新型DEG可能在着床窗口期具有功能意义,并可作为子宫内膜容受性的潜在生物标志物。