Génétique mitochondriale des infertilités masculines

Abstract

Mitochondria play a central role in energy metabolism, homeostasis and apoptosis. These functions are in part under the control of a mitochondrial genome, support of cytoplasmic heredity, whose transmission is only maternal. The involvement of these organelles in human reproduction is a relatively new concept that arouses scientific and medical interest. Abnormalities both qualitative and quantitative of mitochondrial DNA (mtDNA) have been associated with male fertility disorders. Infertility concerns 10 to 15 % of couples wishing to have a child, a male component is found in almost half of cases. In a significant proportion of these cases, a known genetic basis, chromosomal or gene, sometimes transmitted from the parents, is involved. In this work, in a first part, different genetic polymorphisms in humans: (CAG)n POLG1, T3801C CYP1A1 and MTHFR A1298C, and their role as potential risk factors for male infertility in an Algerian population cohort were studied by sequencing or RFLP. Our results show that the variants described at the MTHFR and CYP1A1 genes are not associated with male infertility unlike that of POLG1 which appears to be involved in this dysfunction. In the second part of our work, we have prospected qualitative alterations of mitochondrial genome by analysis of macro-deletions by long PCR and quantitative by quantification of leukocyte mtDNA rate by real-time quantitative PCR (mitochondrial DNA vs nuclear) in idiopathic male infertility. The mtDNA deletion does not appear to be associated with this disorder but the assessment of the level of leukocyte mtDNA likely suggests the involvement of this parameter in male infertility especially in azoospermic and asthenospermic men. Molecular biology has led to the discovery of unexplored etiologies until now without denigrating the clinical and biological explanatory value of many recognized etiologies. This mitochondrial molecular appearance misunderstood opens up new perspectives and may in the future introduce profound changes in the genetic approach to male infertility."