Identification of nonfunctional PABPC1L causing oocyte maturation abnormalities and early embryonic arrest in female primary infertility

Abstract

Oocyte maturation arrest, fertilization failure, and early embryonic arrest are important causes of female infertility, whereas the genetic events that contribute to these processes are largely unknown. Loss‐of‐function of PABPC1L in mice has been suggested to cause female infertility involved in the absence of mature oocytes or embryos in vivo or in vitro. However, the role of PABPC1L in human female reproduction remains largely elusive. In this study, we identified a homozygous missense mutation (c.536G>A, p.R179Q) and a compound heterozygous mutation (c.793C>T, p.R265W; c.1201C>T, p.Q401*) in PABPC1L in two unrelated infertile females characterized by recurrent oocyte maturation abnormalities and early embryonic arrest. These variants resulted in nonfunctional PABPC1L protein and were associated with impaired chromatin configuration and transcriptional silencing in GV oocytes. Moreover, the binding capacity of mutant PABPC1L to mRNAs related to oocyte maturation and early embryonic development was decreased significantly. Our findings revealed novel PABPC1L mutations causing oocyte maturation abnormalities and early embryonic arrest, confirming the essential role of PABPC1L in human female fertility.

Application and discoveries of metabolomics and proteomics in the study of female infertility

“…Ovarian dysfunction includes premature ovarian failure and ovarian cysts. Female infertility symptoms may include irregular, abnormally lengthy, or short menstrual cycles, and difficulty ovulating ( 33 ). Proteomics and metabolomics are two significant omics technologies for studying and diagnosing female infertility.…”