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Relation between sperm protamine transcripts with global sperm DNA methylation and sperm DNA methyltransferases mRNA

Tahereh Rahiminia1, Ehsan Farashahi Yazd2, Saeed Ghasemi-Esmailabad3

  • 1Gametogenesis Research Center, Fertility and Infertility Center, Kashan University of Medical Sciences, Kashan, Iran.

Human Fertility (Cambridge, England)
|April 27, 2019
PubMed

Insights

Severe sperm abnormalities in men are linked to altered DNA methylation and protamine transcript levels. Increased DNA methyltransferases (DNMTs) correlate with higher global DNA methylation and protamine transcripts in these cases.

Area of Science:

  • Reproductive Biology
  • Epigenetics
  • Spermatozoa Function

Background:

  • Sperm DNA methylation patterns are crucial for male fertility.
  • Protamine proteins are essential for sperm DNA packaging and stability.
  • Aberrant DNA methyltransferases (DNMTs) and protamine expression are implicated in male infertility.

Purpose of the Study:

  • To investigate the association between mRNA expression of DNMTs (DNMT1, DNMT3A, DNMT3B) and sperm global DNA methylation.
  • To evaluate the relationship between these epigenetic factors and protamine transcripts (P1, P2) in men with severe sperm abnormalities.

Main Methods:

  • Sperm samples from 30 oligoasthenoteratozoospermic (OAT) and 30 normozoospermic men were analyzed.
  • Real-time quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) was used to measure mRNA expression of DNMTs and protamines.
  • Enzyme-linked immunosorbent assay (ELISA) quantified global DNA methylation levels in sperm.

Main Results:

  • OAT ejaculates showed significantly increased DNMT3A, DNMT3B mRNA, global DNA methylation, and total protamine (P1 + P2) mRNA.
  • A significant decrease in the P1/P2 ratio was observed in OAT samples.
  • Increased protamine transcript levels were associated with elevated DNMT mRNA, and increased DNMT1 may contribute to higher global methylation.

Conclusions:

  • Elevated DNMT3A and DNMT3B mRNA expression, along with increased global DNA methylation and protamine transcripts, characterize severe sperm abnormalities.
  • These findings suggest a potential role for altered DNA methylation and protamine expression in the pathophysiology of male infertility.
  • Targeting DNMTs could be a future avenue for addressing certain male reproductive issues.
Keywords:
DNASpermmethylationprotaminetranscription

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