Abstract

Artificial oocyte activation (AOA) is considered an effective method to improve clinical outcomes in patients with some forms of male factor infertility and does not increase the risk of birth defects. However, the effects of AOA on patients with multiple morphological abnormalities of the sperm flagella (MMAF) caused by a DNAH1 mutation are still unknown. To explore the effects, our study analyzed a case with MMAF due to DNAH1 homozygous mutation that underwent testicular sperm extraction (TESE) combined with intracytoplasmic sperm injection (ICSI). The case had 28 MII oocytes. The 28 oocytes were divided randomly and equally into AOA and non-AOA groups. Ionomycin was used for AOA. We compared the clinical outcomes of two groups and selected three blastulation failure embryos from each group for transcriptome analysis (Data can be accessed through GSE216618). Differentially expressed genes (DEGs) were determined with an adjusted p-value <0.05 and a |log2-fold change| ≥1. The comparison of clinical outcomes showed that the two pronuclei (2PN) rate and grade 1–2 embryo rate at day 3 were not significantly different between the two groups. Transcriptome analyses of blastulation failed embryos showed that the use of AOA had potential risks of chromosome structure defects, transcriptional regulation defects, and epigenetic defects. In conclusion, when the case with MMAF due to DNAH1 mutation underwent TESE-ICSI, ionomycin-induced oocyte activation could not improve the clinical outcomes and introduced the risks of chromosome structure defect, transcriptional regulation defect, and epigenetic defect.

摘要

人工卵母细胞激活 (AOA) 被认为是改善某些形式的男性因素不育症患者临床结果的有效方法，并且不会增加出生缺陷的风险。然而，AOA 对由DNAH1突变引起的多种精子鞭毛形态异常 (MMAF) 患者的影响仍然未知。为了探索这些影响，我们的研究分析了一个由DNAH1引起的 MMAF 病例经睾丸精子提取（TESE）结合胞浆内单精子注射（ICSI）的纯合突变。该病例有 28 个 MII 卵母细胞。将28个卵母细胞随机平均分为AOA组和非AOA组。离子霉素用于 AOA。我们比较了两组的临床结果，并从每组中选择了三个囊胚失败的胚胎进行转录组分析（数据可以通过 GSE216618 访问）。差异表达基因 (DEG) 是用调整后的p确定的-值 <0.05 和 |log2 倍变化| ≥1。临床结局比较显示，两组第3天双原核（2PN）率和1-2级胚胎率无显着差异。对囊胚失败胚胎的转录组分析表明，使用 AOA 存在染色体结构缺陷、转录调控缺陷和表观遗传缺陷的潜在风险。总之，当DNAH1突变所致 MMAF 病例进行 TESE-ICSI 时，离子霉素诱导的卵母细胞激活不能改善临床结果，并引入染色体结构缺陷、转录调控缺陷和表观遗传缺陷的风险。