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Potential Role of CREM in Diabetes-Associated Testicular Dysfunction: Current Evidence and Future Perspectives

Olabimpe Caroline Badejogbin1, Oyedayo Phillips Akano1, Oluwafisayo Elizabeth Boluwatife Julius1

  • 1Department of Physiology College of Basic Medical Sciences, Babcock University Ilishan-Remo Ogun State Nigeria.

Reproductive Medicine and Biology
|June 6, 2025
PubMed
Abstract

Insights

Type 2 diabetes causes male infertility by disrupting testicular function. The cyclic adenosine monophosphate (cAMP) response element modulator (CREM) protein is key to preserving male fertility in diabetic patients.

Area of Science:

  • Reproductive Endocrinology
  • Metabolic Disorders
  • Molecular Biology

Background:

  • Type 2 diabetes mellitus (T2D) is a global metabolic disorder linked to testiculopathy, a primary cause of male infertility.
  • Testiculopathy negatively impacts spermatogenesis and the testicular microenvironment.
  • Cyclic adenosine monophosphate (cAMP) response element modulator (CREM) is crucial for normal testicular function.

Purpose of the Study:

  • To investigate the role of CREM in diabetes-induced testicular dysfunction.
  • To understand the interplay between T2D and CREM dysregulation for potential therapeutic strategies.

Main Methods:

  • A systematic review of preclinical and clinical studies was performed.
  • Databases searched included PubMed, Web of Science, Scopus, and Google Scholar.
  • Data extraction focused on CREM expression, oxidative stress, apoptosis, and spermatogenic impairment in diabetic models.

Main Results:

  • Diabetes negatively affects the reproductive system, including the hypothalamic-pituitary-testicular (HPT) axis.
  • CREM regulates spermatogenic gene expression, influenced by hormones like LH and FSH, and cAMP signaling.
  • CREM disruption is implicated in testiculopathy associated with T2D.

Conclusions:

  • CREM plays a therapeutic role in maintaining testicular function.
  • CREM dysregulation contributes to testiculopathy in T2D, suggesting it as a therapeutic target.
  • Further research is needed to elucidate CREM's molecular mechanisms and therapeutic potential for diabetic male infertility.
Keywords:
CREMmale infertilityreproductionspermatogenesistesticulopathytype 2 diabetes mellitus

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