DAHFMO, Unit of Histology and Medical Embryology, Sapienza, University of Rome, Rome, Italy.
Casa di cura Villa Salaria, Rome, Italy.
J Assist Reprod Genet. 2019 May;36(5):875-887. doi: 10.1007/s10815-019-01410-3. Epub 2019 Feb 1.
To investigate the association of cumulus cell (CC)-related expression of a selected cluster of key genes (PTGS2, CAMK1D, HAS2, STC1, and EFNB2) with embryo development to blastocyst.
Exploratory study at a private clinic. Eighteen advanced maternal age patients were enrolled (37.3 ± 4.0 years). Seventy-five cumuli were collected, whose oocytes resulted in either developmental arrest (N = 33) or blastocyst formation (N = 42). The noninvasive CC gene expression was combined with time-lapse morphokinetic parameters and, for blastocysts, with qPCR-based aneuploidy testing on trophectoderm biopsies.
The detection rate was 100% for all transcripts, but STC1 (96%) and CAMK1D (89%). Among amplified assays, CC mean expression levels of CAMK1D, PTGS2, and HAS2 were higher from oocytes that developed to blastocyst. No difference in CC key gene expression was reported between euploid (N = 21) and aneuploid (N = 21) blastocysts. Some timings of early embryo development were faster in embryos developing to blastocyst (time of pronuclei appearance and fading, division to two- and four-cells, first and second cell cycles). However, the generalized linear models outlined increasing CAMK1D expression levels as the strongest parameter associated with oocytes' developmental potential from both a general (AUC = 0.78 among amplified samples) and an intrapatient perspectives (AUC = 0.9 among patients obtaining ≥ 2 zygotes from the cohort with different developmental outcomes).
CAMK1D level of expression in CCs associated with blastocyst development. If confirmed from larger studies in wider populations of patients, the investigation of CC key gene expression might suit IVF clinics not adopting blastocyst culture. Future investigations should clarify the role of CAMK1D in ovarian physiology and could provide novel insights on how oocytes gain competence during folliculogenesis.
研究选定的一组关键基因（PTGS2、CAMK1D、HAS2、STC1 和 EFNB2）在卵丘细胞（CC）中的相关表达与胚胎发育至囊胚的关系。
在一家私人诊所进行的探索性研究。纳入 18 名高龄产妇（37.3±4.0 岁）。收集了 75 个卵丘，其卵母细胞要么发育停滞（N=33），要么形成囊胚（N=42）。非侵入性 CC 基因表达与时间延迟形态动力学参数相结合，对于囊胚，还与滋养外胚层活检的 qPCR 基础非整倍体检测相结合。
所有转录本的检测率均为 100%，但 STC1（96%）和 CAMK1D（89%）除外。在扩增的检测中，发育至囊胚的卵母细胞的 CC 平均 CAMK1D、PTGS2 和 HAS2 表达水平更高。整倍体（N=21）和非整倍体（N=21）囊胚的 CC 关键基因表达无差异。一些早期胚胎发育的时间在发育至囊胚的胚胎中更快（原核出现和消失的时间、二细胞和四细胞的分裂、第一和第二细胞周期）。然而，广义线性模型概述了随着 CAMK1D 表达水平的增加，卵母细胞的发育潜力与卵丘细胞的发育潜力呈正相关（在扩增样本中 AUC=0.78，在获得不同发育结果的患者队列中从每位患者的角度来看 AUC=0.9）。
CC 中 CAMK1D 的表达水平与囊胚发育相关。如果在更大的患者人群中进行的更大规模研究中得到证实，那么对 CC 关键基因表达的研究可能适合不采用囊胚培养的 IVF 诊所。未来的研究应阐明 CAMK1D 在卵巢生理学中的作用，并为卵母细胞在卵泡发生过程中获得能力提供新的见解。
