Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC, USA.
Fertility Center of the Carolinas, Department of Obstetrics and Gynecology, Prisma Health - Upstate, Greenville, SC, USA.
J Assist Reprod Genet. 2019 Jul;36(7):1457-1469. doi: 10.1007/s10815-019-01489-8. Epub 2019 Jun 11.
To determine whether a selected set of mRNA biomarkers expressed in individual cumulus granulosa cell (CC) masses show association with oocyte developmental competence, embryo ploidy status, and embryo outcomes.
This prospective observational cohort pilot study assessed levels of mRNA biomarkers in 163 individual CC samples from 15 women stimulated in antagonist cycles. Nineteen mRNA biomarker levels were measured by real-time PCR and related to the development of their corresponding individually cultured oocytes and subsequent embryos, embryo ploidy status, and live birth outcomes.
PAPPA mRNA levels were significantly higher in CC from oocytes that led to euploid embryos resulting in live births and aneuploid embryos compared to immature oocytes by ANOVA. LHCGR mRNA levels were significantly higher in CC of oocytes resulting in embryos associated with live birth compared to immature oocytes and oocytes resulting in arrested embryos by ANOVA. Using a general linearized mixed model to assess ploidy status, CC HSD3B mRNA levels in oocytes producing euploid embryos were significantly lower than other oocyte outcomes, collectively. When transferred euploid embryos outcomes were analyzed by ANOVA, AREG mRNA levels were significantly lower and PAPPA mRNA levels significantly higher in CC from oocytes that produced live births compared to transferred embryos that did not form a pregnancy.
Collectively, PAPPA, LHCGR, and AREG mRNA levels in CC may be able to identify oocytes with the best odds of resulting in a live birth, and HSD3B1 mRNA levels may be able to identify oocytes capable of producing euploid embryos.
确定在单个卵丘颗粒细胞 (CC) 中表达的一组选定的 mRNA 生物标志物是否与卵母细胞发育能力、胚胎倍性状态和胚胎结局相关。
本前瞻性观察性队列研究评估了 15 名接受拮抗剂周期刺激的女性的 163 个单个 CC 样本中的 mRNA 生物标志物水平。通过实时 PCR 测量 19 种 mRNA 生物标志物的水平,并将其与相应的个体培养卵母细胞及其随后的胚胎发育、胚胎倍性状态和活产结局相关联。
方差分析显示,导致活产和非整倍体胚胎的卵母细胞的 CC 中 PAPPA mRNA 水平明显高于不成熟卵母细胞。LHCGR mRNA 水平在导致胚胎活产的卵母细胞的 CC 中明显高于不成熟卵母细胞和导致胚胎停滞的卵母细胞。使用广义线性混合模型评估倍性状态,产生整倍体胚胎的卵母细胞的 CC HSD3B mRNA 水平明显低于其他卵母细胞结局。当通过方差分析分析整倍体胚胎移植的结局时,与未形成妊娠的移植胚胎相比,产生活产的卵母细胞的 CC 中 AREG mRNA 水平明显降低,PAPPA mRNA 水平明显升高。
总体而言,CC 中的 PAPPA、LHCGR 和 AREG mRNA 水平可能能够识别出最有可能导致活产的卵母细胞,而 HSD3B1 mRNA 水平可能能够识别出能够产生整倍体胚胎的卵母细胞。