Hassan Sibte, Ashraf Nomia, Hanif Khola, Khan Najeeb Ullah
Reproductive Medicine Physician SEHA Corniche Hospital, Abu Dhabi, UAE.
Department of obstetrics and gynaecology, Fatima Jinnah Medical University Lahore, Lahore, Pakistan.
Mol Biol Rep. 2025 Jan 8;52(1):108. doi: 10.1007/s11033-025-10220-z.
Female infertility is a significant healthcare burden that is frequently encountered among couples globally. While environmental factors, comorbidities, and lifestyle determine reproductive health, certain genetic variants in key reproductive genes can potentially cause unsuccessful pregnancies. Such crucial proteins have been identified within the subcortical maternal complex (SCMC) and play an integral role in the early stages of embryogenesis before embryo implantation. SCMC proteins are associated with crucial pathways during embryogenesis, causing changes that are necessary for the transition of an oocyte to an embryo. These vital processes include the formation of cytoplasmic spindles and lattices, accurate positioning of meiotic spindles, regulatory roles in various gene translations, organelle redistribution, and zygotic genome reprogramming. While these genes are well studied in animal models, often mice, translation to clinical studies is comparatively less. The present study elucidates the transition in genetic studies from animal to human models of SCMC proteins. The present literature review shows that the expression of various SCMC proteins impairs embryo development at different stages. The clinical translation of SCMC occurs via various pathways. Therefore, females experiencing multiple unsuccessful pregnancies after natural or assisted conception techniques are candidates for underlying SCMC mutations. Although the phenotype of affected individuals has been identified, the molecular mechanisms that lead to impaired pathways still require investigation. Therefore, the present study paves the way for future research leading to the early diagnosis of lethal variants and possible subsequent management.
女性不孕症是一个重大的医疗负担，在全球范围内的夫妻中经常遇到。虽然环境因素、合并症和生活方式决定生殖健康，但关键生殖基因中的某些遗传变异可能会导致妊娠失败。这些关键蛋白质已在皮质下母体复合体（SCMC）中被鉴定出来，并在胚胎植入前的胚胎发生早期阶段发挥不可或缺的作用。SCMC蛋白质与胚胎发生过程中的关键途径相关，导致卵母细胞向胚胎转变所必需的变化。这些重要过程包括细胞质纺锤体和晶格的形成、减数分裂纺锤体的准确定位、各种基因翻译中的调节作用、细胞器重新分布以及合子基因组重编程。虽然这些基因在动物模型（通常是小鼠）中得到了充分研究，但转化到临床研究相对较少。本研究阐明了从动物模型到SCMC蛋白质人类模型的遗传学研究转变。目前的文献综述表明，各种SCMC蛋白质的表达在不同阶段会损害胚胎发育。SCMC的临床转化通过多种途径发生。因此，在自然受孕或辅助受孕技术后经历多次妊娠失败的女性是潜在SCMC突变的候选者。虽然已确定受影响个体的表型，但导致途径受损的分子机制仍需研究。因此，本研究为未来导致致命变异早期诊断及后续可能治疗的研究铺平了道路。
