Gene mutations impede oocyte maturation, fertilization, and early embryonic development

Abstract

Reproductive diseases are a long-standing problem and have become more common in the world. Currently, 15% of the world's population suffers from infertility, and half of them are women. Maturation of oocytes, successful fertilization, and high-quality embryos are prerequisites for pregnancy. With the development of assisted reproductive technology and advanced genetic assays, we have found that infertility in many young female patients is caused by mutations in various developmental regulators.These pathogenic factors may result in impediment of oocyte maturation, failure of fertilization or early embryonic development arrest. In this review, we categorize these clinically-identified, mutated genetic factors by their molecular characteristics: nuclear factors (PALT2, TRIP13, WEE2, TBPL2, REC114, MEI1 and CDC20), cytoplasmic factors (TLE6, PADI6, NLRP2/5, FBXO43, MOS and BTG4), a factor unique to primates (TUBB8), cell membrane factor (PANX1), and zona pellucida factors (ZP1-3). We compared discrepancies observed in phenotypes between human and mouse models to provide clues for clinical diagnosis and treatment of related reproductive diseases.

Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review

“…Second, PADI6 is one of the genes encoding the subcortical maternal complex (SCMC), which is necessary for oocyte maturation and early embryonic development. Therefore, the loss and mutation of PADI6 destabilizes SCMC, resulting in abnormal oocyte maturation, fertilization failure, early embryonic developmental arrest, multilocus imprinting disorder, molar pregnancy, miscarriage, and female infertility (32,(190)(191)(192)(193)(194)(195)(196)(197)(198)(199)(200)(201)(202)(203)(204)(205)(206)(207).…”

Editorial: Molecular and cytogenetic research advances in human reproduction

“…Other than such gross chromosomal changes, single-gene mutations have recently received attention as a cause of infertility (8)(9)(10)(11). Indeed, hundreds of mutations have been identified in men suffering from reproductive defects (12,13), and more or less a similar number of mutations have been identified in infertile women (14,15). Such mutations occur in genes responsible for germ cell development and other reproductive processes (16)(17)(18)(19).…”

PADI6: What we know about the elusive fifth member of the peptidyl arginine deiminase family

“…Of the PADI family, PADI6 was the last to be identified and is the least well-characterized. Predominantly expressed in the oocyte and early embryo, PADI6 is crucial for early embryonic development and female fertility in both humans and mice [7,[11][12][13][14][15][16][17][18][19][20][21][22][23][24]. However, the molecular mechanisms responsible for this role are unclear, and notably there is currently no reported catalytic activity of PADI6.…”