Igenomix, Reproductive Genetics, 36063, Marostica, Italy.
Department of Lab Medicine, Unit of Clinical Genetics and Epidemiology, University Hospital of Padova, 35128, Padova, Italy.
J Assist Reprod Genet. 2022 Apr;39(4):847-860. doi: 10.1007/s10815-022-02411-5. Epub 2022 Feb 5.
The most important factor associated with oocytes' developmental competence has been widely identified as the presence of chromosomal abnormalities. However, growing application of genome-wide sequencing (GS) in population diagnostics has enabled the identification of multifactorial genetic predispositions to sub-lethal pathologies, including those affecting IVF outcomes and reproductive fitness. Indeed, GS analysis in families with history of isolated infertility has recently led to the discovery of new genes and variants involved in specific human infertility endophenotypes that impact the availability and the functionality of female gametes by altering unique mechanisms necessary for oocyte maturation and early embryo development. Ongoing advancements in analytical and bioinformatic pipelines for the study of the genetic determinants of oocyte competence may provide the biological evidence required not only for improving the diagnosis of isolated female infertility but also for the development of novel preventive and therapeutic approaches for reproductive failure. Here, we provide an updated discussion and review of the progresses made in preconception genomic medicine in the identification of genetic factors associated with oocyte availability, function, and competence.
与卵母细胞发育能力相关的最重要因素一直被广泛认为是染色体异常的存在。然而,全基因组测序(GS)在人群诊断中的广泛应用,使得人们能够识别出多种遗传易感性的亚致死性病理,包括那些影响 IVF 结局和生殖健康的病理。事实上,对有孤立性不孕史的家族进行 GS 分析,最近发现了新的基因和变体,这些基因和变体涉及特定的人类不孕表型,通过改变卵母细胞成熟和早期胚胎发育所需的独特机制,影响女性配子的可用性和功能。目前,卵母细胞能力遗传决定因素研究的分析和生物信息学管道的不断发展,不仅可能为改善孤立性女性不孕的诊断提供所需的生物学证据,而且可能为生殖失败的新型预防和治疗方法的发展提供所需的生物学证据。在这里,我们提供了一个关于在卵母细胞的可获得性、功能和能力相关的遗传因素的识别方面,在孕前基因组医学方面所取得的进展的更新讨论和综述。