Human infertility: meiotic genes as potential candidates

Up to now, the identification of gene mutations causing infertility in humans remains poorly investigated. Temporal progression through meiosis and meiosis specific genes had been extensively characterized in yeast. Recently some mammalian homologous were found. The molecular mechanisms regulating e...

Full description

Saved in:
Bibliographic Details
Published in:Gynécologie, obstétrique & fertilité obstétrique & fertilité, 2002-10, Vol.30 (10), p.817-821
Main Authors: Mandon-Pépin, B, Derbois, C, Matsuda, F, Cotinot, C, Wolgemuth, D J, Smith, K, McElreavey, K, Nicolas, A, Fellous, M
Format: Article
Language:fre
Subjects:
Adenosine Triphosphatases - genetics
Animals
Cell Cycle Proteins
Cyclin A - genetics
Cyclin A1
DNA-Binding Proteins - genetics
Endodeoxyribonucleases
Esterases - genetics
Female
Humans
Infertility - genetics
Male
Meiosis - genetics
Mice
Mutation
Nuclear Proteins
Proteins - genetics
Space life sciences
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Up to now, the identification of gene mutations causing infertility in humans remains poorly investigated. Temporal progression through meiosis and meiosis specific genes had been extensively characterized in yeast. Recently some mammalian homologous were found. The molecular mechanisms regulating entry into and progression through meiosis in mammals are still unknown. However, disruption of some meiotic genes in mouse showed an essential role of them in meiotic chromosome synapsis and gametogenesis. Moreover, the phenotype of gonads in null mutant mice for some meiotic genes (failure to initiate or blockage in meiosis, lack of gametes or small size of gonads...) could be strikingly similar to clinical observations found in human infertility. The aim of this study was to identify putative mutations in 5 meiotic genes of several clinically well-characterized patients who present unexplained infertility (normal karyotype, women with premature ovarian failure, men with azospermia and without Y micro-deletion). For this purpose, the exons of these 5 genes (DMC1, SPO11, MSH4, MSH5, CCNA1) were all amplified by PCR with specific primers and each amplified-exon was sequenced. Sequences were aligned in comparison to the human corresponding gene available in Genbank. Many heterozygous mutations were found in different genes. Two homozygous mutations were found in MSH4 and DMC1 genes in a young man presenting a testis vanishing syndrome and a woman presenting a premature ovarian failure, respectively. Consequences of such mutations will be examined and verified in model organisms (yeast, mouse) to check the relevance of the mutations in clinical setting.
ISSN:1297-9589