Guo Luyan, Gu Fang, Xu Yan, Zhou Canquan
Department of Obstetrics and Gynecology, Sun Yat-Sen University First Affiliated Hospital, Guangzhou, Guangdong, China.
Reproductive Medical Center, Department of Obstetrics and Gynecology, Sun Yat-Sen University First Affiliated Hospital, Guangzhou, Guangdong, China.
PeerJ. 2020 Nov 17;8:e10368. doi: 10.7717/peerj.10368. eCollection 2020.
A key step in embryo implantation is the adhesion to and invasion of the endometrium by the blastocyst trophectoderm. The envelope proteins of HERV-W and -FRD (human endogenous retrovirus-W and -FRD), syncytin-1 and syncytin-2, are mainly distributed in the placenta, and play important roles in the development of the placenta. The placenta originates from the trophectoderm of the blastocyst. It is unclear whether the envelope proteins of HERV-W and -FRD have an effect on the development of the trophectoderm and whether they have any association with the implantation of the blastocyst.
The whole-genome amplification products of the human blastocyst trophectoderm were used to measure the copy number of syncytin-1 and syncytin-2 using real time qPCR. In addition, clinical data associated with the outcome of pregnancies was collected, and included age, body mass index (BMI), basic follicle stimulating hormone(bFSH), rate of primary infertility and oligo-astheno-teratospermia, the thickness of the endometrium on the day of endometrial transformation, the levels of estrogen and progestin on the transfer day, the days and the morphological scores of the blastocysts. The expression of mRNA and the copy numbers of syncytin-1 and syncytin-2 in H1 stem cells, and in differentiated H1 cells, induced by BMP4, were measured using real time qPCR.
The relative copy number of syncytin-1 in the pregnant group (median: 424%, quartile: 232%-463%, < 0.05) was significantly higher than in the non-pregnant group (median: 100%, quartile: 81%-163%). There was a correlation ( = 0.681, < 0.001) between the copy number of syncytin-1 and blastocyst implantation after embryo transfer. As the stem cells differentiated, the expression of NANOG mRNA decreased, and the expression of caudal type homeobox 2(CDX2) and -human chorionic gonadotropin (-hCG) mRNAs increased. Compared to the undifferentiated cells, the relative expression of the syncytin-1 mRNA was 1.63 (quartile: 0.59-6.37, > 0.05), 3.36 (quartile: 0.85-14.80, > 0.05), 10.85 (quartile: 3.39-24.46, < 0.05) and 67.81 (quartile: 54.07-85.48, < 0.05) on day 1, 3, 5 and 7, respectively, after the differentiation. The relative expression of syncytin-2 was 5.34 (quartile: 4.50-10.30), 7.90 (quartile: 2.46-14.01), 57.44 (quartile: 38.35-103.87) and 344.76 (quartile: 267.72-440.10) on day 1, 3, 5 and 7, respectively, after the differentiation ( < 0.05). The copy number of syncytin-1 increased significantly during differentiation.
Preceding the transfer of frozen embryos, the increased copy number of syncytin-1 in the blastocyst trophectoderm was associated with good outcomes of pregnancies.
胚胎植入的关键步骤是囊胚滋养外胚层对子宫内膜的黏附和侵入。人内源性逆转录病毒-W和-FRD（HERV-W和-FRD）的包膜蛋白，即合胞素-1和合胞素-2，主要分布在胎盘，在胎盘发育中起重要作用。胎盘起源于囊胚的滋养外胚层。尚不清楚HERV-W和-FRD的包膜蛋白是否对滋养外胚层的发育有影响，以及它们与囊胚植入是否存在关联。
用人囊胚滋养外胚层的全基因组扩增产物，通过实时定量PCR测量合胞素-1和合胞素-2 的拷贝数。此外，收集与妊娠结局相关的临床数据，包括年龄、体重指数（BMI）、基础卵泡刺激素（bFSH）、原发不孕率和少弱畸精子症、子宫内膜转化日的子宫内膜厚度、移植日的雌激素和孕激素水平、囊胚的天数和形态学评分。用实时定量PCR测量BMP4诱导的H1干细胞及分化的H1细胞中合胞素-1的mRNA表达及合胞素-1和合胞素-2的拷贝数。
妊娠组合胞素-1的相对拷贝数（中位数：424%，四分位数：232%-463%，<0.05）显著高于非妊娠组（中位数：100%，四分位数：81%-163%）。合胞素-1的拷贝数与胚胎移植后囊胚植入之间存在相关性（r = 0.681，<0.001）。随着干细胞分化，NANOG mRNA的表达降低，尾型同源盒2（CDX2）和人绒毛膜促性腺激素（-hCG）mRNA的表达增加。与未分化细胞相比，分化后第1、3、5和7天合胞素-1 mRNA的相对表达分别为1.63（四分位数：0.59-6.37，>0.05）、3.36（四分位数：0.85-14.80，>0.05）、10.85（四分位数：3.39-24.46，<0.05）和67.81（四分位数：
