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Published on: January 26, 2024
Protective effects of cornus mas extract on in vitro fertilization potential in methotrexate treated male mice
Leila Zarei1, Rasoul Shahrooz2, Rajabali Sadrkhanlou2
1Solid Tumor Research Center, Urmia University of Medical Science, Urmia, Iran;
Abstract:
Current study was aimed to evaluating protective effects of cornus mas fruit extract (CMFE) in mice treated with methotrexate (MTX). For this purpose, 48 young mature male mice were divided into 6 groups. Control group received only normal saline (0.1 mL per day, intraperitoneally), and the second group was administered MTX (20 mg kg(-1) per week, intraperitoneally). The third, fourth and fifth groups received MTX daily oral doses of 250, 500 and 1000 mg kg(-1) CMFE as well as MTX. The sixth group was only given CMFE with a dose of 1000 mg kg(-1) per day, orally, for 35 days. Then, the animals were anesthetically euthanized and the sperms were separated from epididymis. DNA damage level, the amount of malondialdehyde (MDA) as well as in vitro fertility was evaluated. The number of sperms with damaged DNA and MDA level in MTX-treated group showed a significant increase compared to control group (p < 0.05). In groups receiving CMFE along with MTX, DNA damage level and MDA amount suggested a decrease in comparison with MTX group (p < 0.05). Also, in vitro fertilization and embryonic development in MTX-treated group was significantly lower than the control group, and the level of embryonic arresting was higher (p < 0.05). In groups which received CMFE along with MTX, in vitro fertility and embryonic development was higher than MTX group (p < 0.05) and the arrested embryos showed a decrease. This study suggested that cornus mas is able to ameliorate the side effects of MTX.
Insights
Cornus mas fruit extract (CMFE) protects against methotrexate (MTX) induced testicular toxicity in mice. CMFE reduced sperm DNA damage and improved in vitro fertility, mitigating MTX side effects.
Area of Science:
- Reproductive Toxicology
- Natural Product Chemistry
- Pharmacology
Background:
- Methotrexate (MTX) is a chemotherapy agent with known reproductive toxicity.
- Oxidative stress and DNA damage are key mechanisms underlying MTX-induced testicular dysfunction.
- Cornus mas fruit extract (CMFE) is investigated for its potential protective properties.
Purpose of the Study:
- To evaluate the protective effects of CMFE against MTX-induced testicular toxicity in male mice.
- To assess CMFE's impact on sperm DNA damage, malondialdehyde (MDA) levels, and in vitro fertility.
Main Methods:
- Male mice were divided into six groups: control, MTX-only, and four groups receiving MTX with varying doses of CMFE (250, 500, 1000 mg/kg) or CMFE-only.
- Treatment duration was 35 days.
- Sperm DNA damage, MDA levels, and in vitro fertilization/embryonic development were assessed post-treatment.
Main Results:
- MTX treatment significantly increased sperm DNA damage and MDA levels compared to controls.
- CMFE administration, particularly at higher doses, significantly reduced DNA damage and MDA levels in MTX-treated mice.
- In vitro fertilization rates and embryonic development were significantly impaired by MTX but improved with CMFE co-administration.
Conclusions:
- Cornus mas fruit extract (CMFE) demonstrates significant protective effects against methotrexate (MTX)-induced testicular toxicity.
- CMFE ameliorates MTX-induced oxidative stress and DNA damage, thereby improving sperm quality and reproductive parameters.
- CMFE holds potential as a complementary agent to mitigate the reproductive side effects of MTX therapy.

