Methoxsalen deteriorative effects on the testicular parenchyma and testosterone synthesis gene expression in male

Zahra Gholipour1, Abbas Fazlinia2, Farhad Koohpeyma3,4

  • 1Department of Genetics, Zarghan Branch, Islamic Azad University, Shiraz, Iran.

Scientific Reports
|December 14, 2025
PubMed

Insights

Methoxsalen combined with UVA negatively impacts rat reproductive health, reducing testosterone and sperm quality. High doses increase damage and alter gene expression, suggesting caution for pregnancy planning.

Area of Science:

  • Reproductive Toxicology
  • Pharmacology
  • Genetics

Background:

  • Psoralens, including methoxsalen, are known to have adverse effects on the reproductive system.
  • Investigating the specific impact of methoxsalen and UVA on male reproductive parameters is crucial.

Purpose of the Study:

  • To evaluate the effects of methoxsalen and UVA on testicular function, sperm quality, and testosterone synthesis gene expression in rats.
  • To determine dose-dependent toxicity of methoxsalen and UVA on the male reproductive system.

Main Methods:

  • Adult male rats were exposed to varying doses of methoxsalen plus UVA radiation.
  • Hormone levels (LH, FSH, Testosterone), sperm parameters (quality, quantity, motility, viability), testicular histology, and gene expression (STAR, Cyp11a1, Hsd17b3, Bcl-2, Caspase-9) were analyzed.
  • Stereological analysis was used to assess structural changes in testicular tissue.

Main Results:

  • Methoxsalen and UVA significantly reduced testosterone levels, sperm parameters, and testicular weight/volume.
  • A decrease in the volume of Leydig cells and reduced mRNA expression of key testosterone synthesis genes (STAR, Cyp11a1, Hsd17b3) and Bcl-2 were observed.
  • High methoxsalen doses led to increased Caspase-9 mRNA expression and elevated LH/FSH levels, indicating potential testicular damage and hormonal disruption.

Conclusions:

  • Methoxsalen in combination with UVA causes detrimental effects on the male rat reproductive system, particularly at higher doses.
  • The drug combination impairs testosterone synthesis pathways and sperm parameters, advising against its use for individuals planning pregnancy.
  • Further research is warranted to fully elucidate the long-term reproductive consequences.