卵母细胞丘细胞中的卵泡大小与基因表达之间是否存在相关性，基因表达是否是胚胎发育的指标？
Is there a correlation between follicle size and gene expression in cumulus cells and is gene expression an indicator of embryo development?
机构信息
Istanbul Memorial Hospital, Assisted Reproductive Technologies and Reproductive Genetics Centre, Piyale Pasa Bulvari 34385 Okmeydani Sisli, Istanbul, Turkey.
ilabcomm GmbH, Eisenachstr. 34, 53757, Sankt Augustin, Germany.
出版信息
Reprod Biol Endocrinol. 2018 Jul 21;16(1):69. doi: 10.1186/s12958-018-0388-0.
BACKGROUND
In an article published in 2017, we discussed the results of the first part of our study into the morphokinetic development of embryos in relation to follicle diameter and homogeneity of follicular development. Our findings showed that embryos coming from small follicles in heterogeneous cycles had significantly higher rates of arrest or failure to reach blastocyst than embryos coming from large follicles in homogenous cycles. The aim of this further study was to investigate the relationship between follicular size and gene expression of cumulus cells (CCs) and evaluate whether gene expression could be an indicator of embryo development.
METHODS
This study was based on 2495 COCs from 184 patients. CC expressions of five genes (TNFAIP6, PTGS2, HAS2, PTX3 and GDF9) were studied by generalized linear mixed models (GLMMs) regarding follicular size. CC expressions were then separately analysed regarding patient-specific variables (age, BMI, AMH and follicular size) in relation to embryos reaching blastocyst (eRB) or top or good quality blastocysts (TQ + GQ) using GLMMs with logit link.
RESULTS
Follicular size significantly correlated with the potential of an oocyte to develop into a blastocyst: oocytes developing from large follicles were more than twice as likely to develop into an eRB than oocytes from small follicles (p < 0.001). Gene expression of HAS2 and GDF9 correlated with blastocyst quality when separately evaluated with follicular size and the patient specific variables of age, BMI and AMH. However, no such correlation was found in other gene expressions studied.
CONCLUSIONS
Our findings suggest that differences in the expression of genes studied could be related to follicular size rather than to embryo quality. Although gene expression of HAS2 and GDF9 correlated with blastocyst quality, the only variable correlating with eRB and TQ and GQ blastocysts for each of these five models was follicular size.
TRIAL REGISTRATION
This prospective cohort study was registered at clinicaltrials.gov (NCT02230449).
背景
在 2017 年发表的一篇文章中，我们讨论了我们对胚胎形态动力学发育与卵泡直径和卵泡发育均匀性关系的研究的第一部分结果。我们的发现表明，来自异质周期中小卵泡的胚胎，其阻滞或未能达到囊胚的比例明显高于同质周期中来自大卵泡的胚胎。本进一步研究的目的是探讨卵泡大小与卵丘细胞（CC）基因表达的关系，并评估基因表达是否可以作为胚胎发育的指标。
方法
本研究基于 184 名患者的 2495 个 COC。使用广义线性混合模型（GLMM）研究了五个基因（TNFAIP6、PTGS2、HAS2、PTX3 和 GDF9）的 CC 表达与卵泡大小的关系。然后，使用对数链接的 GLMM，分别分析了 CC 表达与患者特定变量（年龄、BMI、AMH 和卵泡大小）与胚胎达到囊胚（eRB）或优质囊胚（TQ+GQ）的关系。
结果
卵泡大小与卵母细胞发育成囊胚的潜力显著相关：来自大卵泡的卵母细胞发育成 eRB 的可能性是来自小卵泡的卵母细胞的两倍多（p<0.001）。当单独评估卵泡大小和患者特定变量（年龄、BMI 和 AMH）时，HAS2 和 GDF9 的基因表达与囊胚质量相关。然而，在研究的其他基因表达中未发现这种相关性。
结论
我们的研究结果表明，所研究基因的表达差异可能与卵泡大小有关，而与胚胎质量无关。尽管 HAS2 和 GDF9 的基因表达与囊胚质量相关，但这五个模型中唯一与 eRB 和 TQ 和 GQ 囊胚相关的变量是卵泡大小。
试验注册
本前瞻性队列研究在 clinicaltrials.gov 注册（NCT02230449）。
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