Female infertility from oocyte maturation arrest: assembling the genetic puzzle

Abstract

Assisted reproduction procedures often encounter an issue called oocyte maturation arrest (OMA), which is manifested as failed IVF/ICSI attempts using oocytes from some infertile women. In this issue of EMBO Molecular Medicine, Wang et al identify infertile women bearing novel DNA sequence variants in a gene called PABPC1L, which is essential for translation of maternal mRNAs. By conducting a series of in vitro and in vivo experiments, they demonstrated certain variants as being causal for OMA, confirming a conserved requirement for PABPC1L in human oocyte maturation. This study offers a promising therapeutic target for treating OMA patients.

Figure 1. Unpuzzling PABPC1L variants in women with oocyte maturation arrest

This study utilized a systematic process to confirm the genetic causality of PABPC1L variants in patients with OMA. It was accomplished by assembling four pieces of puzzle: (1) clinical investigations of patient history and IVF phenotype; (2) sequencing and in silico analysis to identify candidate variants; (3) in vitro analysis of PABPC1L variants for altered behavior; and (4) generation and analysis of mouse models for variants. The figure was created in part using BioRender.