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Estrogen Receptor Signaling Alters Sperm DNA Methylation Landscape in Adult Male Rats.

Kushaan Khambata1, Sanketa Raut2, Priyanka Parte1

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Estrogen signaling via ERα and ERβ significantly alters the sperm epigenome, impacting male fertility. Aberrant estrogen signaling may contribute to male infertility conditions by affecting sperm DNA methylation patterns.

Keywords:
DNA methylationestrogen receptorspermtestiswhole genome bisulfite sequencing

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Area of Science:

  • Reproductive Biology
  • Epigenetics
  • Endocrinology

Background:

  • Estrogen receptors (ERα and ERβ) play a crucial role in regulating spermatogenesis and male fertility.
  • The sperm epigenome, particularly DNA methylation, is vital for male reproductive success.
  • Understanding how estrogen signaling influences the sperm epigenome is key to deciphering male infertility causes.

Purpose of the Study:

  • To investigate the impact of estrogen receptor (ER) signaling activation on the sperm DNA methylome in adult rats.
  • To compare the effects of ERα and ERβ activation on global DNA methylation patterns in sperm.
  • To identify differentially methylated genes (DMGs) and assess their expression changes in the testis.

Main Methods:

  • Whole genome-bisulfite sequencing (WGBS) was performed on caudal sperm DNA from adult rats.
  • Differential DNA methylation sites (DMCs) were identified and validated using pyrosequencing.
  • Gene expression analysis of DMGs was conducted in testicular tissue via quantitative RT-PCR.

Main Results:

  • ERα signaling activation (using PPT) induced substantial changes in the sperm methylome, identifying 28,074 DMCs and 5,189 DMGs.
  • ERβ signaling activation (using DPN) resulted in fewer changes, with 1,492 DMCs and 336 DMGs identified.
  • Most DMCs were located in intronic, promoter, and upstream regions, affecting genes crucial for spermatogenesis, with altered expression observed in the testis.

Conclusions:

  • Estrogen signaling through ERα significantly shapes the sperm epigenome, influencing DNA methylation patterns.
  • Aberrant estrogen signaling, particularly via ERα, may contribute to male infertility by altering the sperm methylome.
  • The findings highlight the critical role of ERs in maintaining male fertility through epigenetic regulation of sperm DNA.