Unexplained recurrent miscarriages are associated with an aberrant sperm protamine mRNA content

Area of Science:

• Reproductive Biology
• Spermatozoa Research
• Genetics and Epigenetics

Background:

• Aberrant sperm protamine ratios are linked to male infertility.
• The role of protamine mRNA levels in recurrent miscarriage (RM) is not fully understood.

Purpose of the Study:

• To investigate the association between protamine-1 and protamine-2 mRNA levels in spermatozoa and unexplained recurrent miscarriages.
• To determine if protamine mRNA ratios in spermatozoa differ between men with RM and control groups.

Main Methods:

• Spermatozoa were collected from men with RM, healthy donors, and men undergoing IVF/ICSI.
• Reverse transcription quantitative PCR (RTqPCR) was used to analyze protamine-1 and protamine-2 mRNA levels.
• Semen parameters were also assessed and correlated with protamine mRNA levels.

Main Results:

• Protamine-1 and protamine-2 mRNA levels and their ratio were significantly different in men with RM compared to healthy controls (P < 0.01).
• Men with RM showed significantly higher protamine mRNA Ct-values and a lower protamine mRNA ratio compared to couples undergoing IVF/ICSI (P < 0.01).
• Significant negative correlations were found between progressive motility and protamine-2 mRNA levels, and non-progressive motility and the protamine mRNA ratio.

Conclusions:

• Spermatozoa protamine mRNA levels and ratios are significantly altered in men experiencing recurrent miscarriages.
• These alterations suggest a potential role for protamine mRNA in early embryo development, extending beyond its known association with male infertility.