Combinations of genetic changes in the human cAMP-responsive element modulator gene: a clue towards understanding...

Area of Science:

• Reproductive biology
• Human genetics
• Molecular endocrinology

Background:

• The cAMP-responsive element modulator (CREM) gene is crucial for mouse spermatogenesis.
• Its specific role in human infertility remains largely uncharacterized.

Purpose of the Study:

• To investigate the role of CREM gene mutations in human male infertility, specifically in cases of round spermatid arrest.
• To identify genetic variations within the CREM gene in infertile Slovenian men.

Main Methods:

• Mutation screening of the CREM gene in 13 Slovenian men with round spermatid arrest and 6 controls.
• Identification and characterization of genetic changes, including single-nucleotide polymorphisms (SNPs), insertions, and nonsense mutations.
• Analysis of a patient with no CREM protein and assessment of nuclear protein binding affinity for identified mutations.

Main Results:

• Eleven genetic alterations were found in the human CREM gene, including three novel SNPs, one insertion (IVS2), and one nonsense mutation (exon gamma).
• A patient with no detectable CREM protein was homozygous for multiple nucleotide changes and heterozygous for an exon gamma mutation.
• An insertion in IVS2 (IVS2-58_55insT) led to a four-fold reduction in nuclear protein binding.

Conclusions:

• The study identified several genetic changes in the CREM gene, some potentially contributing to male infertility.
• Further research with larger cohorts is necessary to confirm the association between CREM gene variations and male infertility.
• The findings highlight the potential impact of CREM gene mutations on spermatogenesis and male reproductive health.