# Letrozole and Crocin: Protecting Leydig Cells and Modulating Androgen Receptor and CYP19 Gene Expression in Busulfan-Induced Azoospermia

**Authors:** Shahrzad Nokhbeh Zaeem, Mitra Heydari Nasrabadi, Masoud Salehipour, Somayeh Ehtesham

PMC · DOI: 10.3390/ani15050697 · 2025-02-27

## TL;DR

This study found that letrozole and crocin may help protect testicular cells and improve hormone balance in rats with busulfan-induced infertility, though more research is needed.

## Contribution

The study introduces a novel combination of letrozole and crocin to modulate androgen receptor and CYP19 gene expression in busulfan-induced azoospermia.

## Key findings

- Combination treatment reduced testicular fibrosis to approximately 15%.
- The treatment increased antioxidant enzyme activity and upregulated androgen receptor expression.
- Leydig cell morphology was preserved better in treated groups compared to the azoospermia group.

## Abstract

This study explored the impact of letrozole and crocin on Leydig cells in male rats with azoospermia induced by busulfan, a chemotherapy drug used to treat certain cancers. Azoospermia is a condition where sperm is absent in semen and is a major cause of male infertility. Researchers used rats during the experiments, dividing them into different groups. The rats received letrozole, crocin, or both after exposure to busulfan. The study found that while letrozole and crocin did not significantly restore cell viability, they improved sperm motility. The combination treatment also enhanced antioxidant activity, which protects against oxidative stress. Additionally, the treatment increased androgen receptor expression and CYP19A gene activity, both important for hormone balance and sperm production. In contrast, the busulfan-treated rats showed significant declines in these markers, indicating damage to testicular function. The findings suggest that letrozole and crocin may work together to support recovery from azoospermia. However, further research is needed to fully understand their effectiveness and potential for clinical use in male infertility treatment.

This study aimed to investigate the impact of letrozole and crocin on Leydig cells on busulfan-induced azoospermia using a rat model. A sample population consisting of thirty male rats was randomly assigned to five groups: (1) the control group, (2) azoospermia group, (3) azoospermia group treated with letrozole, (4) azoospermia group treated with crocin, and (5) azoospermia group treated with both letrozole and crocin. The treatment period with letrozole and crocin lasted for four weeks following busulfan administration. Subsequently, comprehensive analyses, including histopathological, molecular, and hormonal assessments, were performed, followed by immunohistochemical staining. This study found that the control group exhibited normal Leydig cell morphology, while the azoospermia group showed reduced Leydig cells and tissue disruptions. Letrozole and crocin treatments were associated with increased testicular fibrosis in the AZO and AZO + Cro groups, while their combination notably reduced fibrosis to approximately 15%. Furthermore, the combination treatment enhanced antioxidant enzyme activity and upregulated androgen receptor expression. Although a number of improvements were noted in sperm motility, they were not statistically significant. Further research is required to clarify the therapeutic implications of these findings in azoospermia treatment.

## Linked entities

- **Genes:** CYP19A (peptidyl-prolyl cis-trans isomerase, putative) [NCBI Gene 39732473]
- **Chemicals:** letrozole (PubChem CID 3902), crocin (PubChem CID 5281233), busulfan (PubChem CID 2478)
- **Diseases:** azoospermia (MONDO:0100459)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Cyp19a1 (cytochrome P450, family 19, subfamily a, polypeptide 1) [NCBI Gene 25147] {aka Aromatase, Cyp19, Cyp19a, p450arom}, Ar (androgen receptor) [NCBI Gene 24208] {aka Andr, Tfm}
- **Diseases:** fibrosis (MESH:D005355), Azoospermia (MESH:D053713)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11898426/full.md

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Source: https://tomesphere.com/paper/PMC11898426