Testing for cytoplasmic abnormalities: Mitochondrial haplogroup and aneuploidy any correlation?

Introduction It is well known that oocyte aneuploidy, that originates from chromosome/chromatids segregation errors during oogenesis, negatively affects reproductive outcomes. Similarly, the abundance of functioning mitochondria which are deputed to the production of energy through the synthesis of ATP, has a strong effect on oocyte quality. The provision of energy is actually crucial for all cellular metabolic processes including the occurrence of a correct meiotic division. Recent data have shown that the amount of cellular ATP may be influenced by the mitochondrial haplogroup, whose variants mediate not only cell growth through the production of energy, but also cell signaling for major molecular pathways. In other words, mtDNA variants play important roles in most cellular functions and pathological conditions. The aim of this study was to assess the oocyte chromosomal status through the analysis of the corresponding polar bodies (PBs) and to evaluate any possible association between aneuploidy and the mitochondrial haplogroup. Materials and methods Whole Genome Amplification (WGA) of 89 PBs from 13 patients (mean age 40.2±1.5 years) was performed using the SurePlex™ amplification kit (Rubicon). Aneuploidy was assessed by array-Comparative Genomic Hybridization (CGH). Haplogroups were inferred using the HaploGrep software (http://haplogrep.uibk.ac.at/) by matching HVSI haplotypes with the most recent literature data from mtDNA tree Build 12 (http://www.phylotree.org/). Results Of the 89 studied PBs, 21 were euploid (11 PB1 and 10 PB2) and 68 aneuploid (36 PB1 and 32 PB2). Five different haplogroups were found, namely H (the most common haplogroup in Europe), J, T, K and U, each including several variants. Conclusion Literature data show that haplogroup J and T are associated with an increased risk of developing different degenerative diseases, while haplogroup H seems to act as a protective haplogroup. A similar trend was observed in the incidence of aneuploidy as the sister haplogroups J/T (belonging to the super-haplogroup R together with the sister haplogroups U/K) presented a significantly higher incidence of chromosome errors when compared with haplogroup H. More in detail, in the haplogroup J losses occurred more frequently than gains, whereas the two figures were similar in haplogroup H. Looking at the molecular level, it was reported that the efficiency of the electron transport chain and the ATP production were diminished in haplogroup J in comparison with haplogroup H. Since ATP is crucial for a correct chromosome segregation, it may be speculated that different haplogroups may affect the meiotic process through a diverse level of ATP production.