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The burden of male infertility is often unrecognized and its causes are poorly understood. Efforts to increase awareness and understanding are being undertaken to improve fertility outcomes and overall health for affected men.
Much of the Y chromosome has remained obscure owing to the challenge of sequencing repetitive genomic regions. Recently, the Y chromosome has been fully sequenced, revealing extensive heterochromatic areas and 41 new protein-coding genes. Furthermore, 43 Y chromosomes have been sequenced, showing extensive multi-sample variation and providing promising insights into male infertility.
Understanding the cell-type-specific mechanisms of cellular dysfunction is necessary to develop precision medicine strategies that promote regeneration of spermatogenesis. In this Review, the authors discuss mechanisms of cellular dysfunction that have been elucidated in non-obstructive azoospermia testicular cells, in both somatic cells and germ cells, and consider how identifying modulators of cellular transcription and translation will be key for future research.
In this Expert Recommendation, the authors provide a standardized nomenclature to improve the Human Phenotype Ontology tree with regard to the classification of non-syndromic male infertility. The implications of introducing this vocabulary in promoting communication across disciplines and institutions and in discovering novel genetic causes of non-syndromic male infertility are also discussed.
In this Expert Recommendation, the most pressing questions related to male reproductive health, spanning the spectrum of andrology, are identified. These questions encompass and highlight many opportunities to influence the wellness of future generations.