Is there a relationship between the oocyte cytoplasmic maturation, metaphase plate conformation and aneuploidies?

Abstract

Nuclear and cytoplasmic oocyte maturation occurs in vivo during follicular growth and ovulation. Both processes are induced by changes in plasma levels of gonadotropins. During their growth, oocytes acquire the ability to restart meiotic maturation in response to gonadotropins stimulation, mainly LH increased. The nuclear envelope breaks down, the first polar body is released and meiosis progress until metaphase II (MII). The meiosis stops in MII and ovulation occurs. Maturation promoting factor (MPF) and mitogen activated protein kinases (MAPK) play an important role in oocyte maturation.Our group have previously reported that cdc2 phosphorilated in Y15 could be a good marker during oocyte meiosis. Thus, when the oocyte reach the MII stage cdc2-Y15 is very imperceptible, contrary in oocytes going through to MI to MII, cdc2-Y15 levels are high (1)(2). Prospective comparative study. Remanent oocytes were obtained from IVF cycles (2013-2016) under informed consent. From 68 patients, 42 MII and 64 unfertilized oocytes after ICSI were studied.The first polar body was collected for chromosomal analysis by aCGH (comparative genomic hybridization) and NGS (next generation sequencing). The remaining oocytes were processed by immunocytochemistry-ICC to determine oocyte maturation: assessment of inactive MPF (cdc2 - Y15) status and the metaphase plate alignment (Hoechst).Two groups were conformed according to the main feature observed: A: cytoplasmic immaturity and B: mature cytoplasm. Regarding MII - B (26), 89% (23) had a normal metaphase plate and 87% (20) were chromosomally eupolid. Contrary, in A oocytes (16), 38% (6) presented a normal metaphase plate and just 33% (2) were euploid.In unfertilized oocytes after ICSI: 92% (24) of mature oocytes (B) (26) had a normal metaphase plate and 83% (20) were euploid. When oocytes had a cytoplasmic immaturity (38), 37% (14) had a normal metaphase plate and 43% (6) were chromosomally normal.The global rate of aneuploidies and metaphase plate disarrangements in immature oocytes (MII+failed-fertilized) were significantly higher than mature oocytes (p<0.05). Our results suggest that cytoplasmic oocyte maturation has a higher relevance compared to nuclear maturity. An inadequate cytoplasmic maturation is associated with altered levels of metaphase plate alignment and aneuploidies.