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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.
Abstract:
Studies show that psoralens have adverse effects on the reproductive system. This study investigated the impact of methoxsalen in combination with UVA on testicular parenchyma and the expression level of testosterone synthesis pathway genes as well as sperm quality and quantity, in rats. 24 adult male rats were randomly divided into 4 groups: control, sham group receiving the same volume of the corn oil + ultraviolet radiation (UVA): 0.046 J/cm2, for 20 min, and experimental groups receiving 37.5, and 75 mg/kg doses of Methoxalen + UVA, respectively (MTX 37.5 and MTX 75). After 48 days' serum samples were separated to measure the concentrations of LH, FSH, and Testosterone hormones. Spermatozoa were obtained from the epididymis for analysis of quality, quantity, morphology, viability and motility. Additionally, testicular tissue was subjected to stereological analysis to evaluate structural changes, and mRNA expression levels of STAR, Cyp11a1, Hsd17b3, Bcl-2, and Caspase-9 were measured. The results show detrimental effects of MTX in testosterone, sperm parameters, weight, and volume of the testis. Also, the volume of sperm and testosterone-producing cells such as Leydig cells decreased after treatment. The expression level of STAR, Cyp11a1, Hsd17b3, and Bcl-2 mRNAs were diminished, though the mRNA expression of caspase-9 and serum level of LH, and FSH in the high dose of the methoxsalen group increased compared to the sham group. Administering methoxsalen along with UVA can cause more severe damage to testicular parenchyma at high doses and reduce the mRNA expression level of genes involved in the testosterone synthesis pathway. Therefore, administering this drug is not recommended for people who are planning to become pregnant, although more studies are needed in this field.
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.
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