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Effects of exendin-4 on male reproductive parameters of d-galactose induced aging mouse model
Akram Ahangarpour1, Ali Akbar Oroojan2, Hamid Heidari3
1Health Research Institute, Diabetes Research Center, Department of Physiology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Purpose:
The purpose of this study was to evaluate the role of exendin-4 on reproductive alteration in a D-galactose-induced aging mouse model.
Materials And Methods:
In this experimental study, 72 male Naval Medical Research Institute mice (20~25 g) were randomly divided into six groups: control, exendin-4 (1 nmol/kg), exendin-4 (10 nmol/kg), D-galactose (500 mg/kg), D-galactose+exendin-4 (1 nmol/kg), and D-galactose+exendin-4 (10 nmol/kg). The aging model animals were gavaged with D-galactose for six weeks, and exendin-4 was injected intraperitoneally in the last 10 days. At the end of treatment serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone levels were evaluated and the cauda epididymis and testis were removed to analyze the sperm count and testis morphology.
Results:
The testis weight and volume decreased in the D-galactose group (p<0.01 and p<0.05) respectively. Exendin-4 (1, 10 nmol/kg) increased these parameters in the normal and aging mouse models. Serum LH and FSH levels increased and the sperm count decreased in the D-galactose group (p<0.05). Further, exendin-4 (1 nmol/kg) decreased LH and FSH levels and increased the serum testosterone level and sperm count in both normal and aging animals.
Conclusions:
D-galactose can induce aging alternations in the male reproductive system such as decreased sperm count and increased serum LH and FSH levels through reactive oxygen species over production and reduced antioxidant enzyme activity. Further, co-administration of exendin-4 reduced reproductive complications of D-galactose in an aging mouse model.
Insights
Exendin-4 treatment mitigated D-galactose-induced male reproductive aging in mice. It improved sperm count and testosterone levels while reducing harmful reproductive alterations in this aging model.
Area of Science:
- Reproductive Biology
- Aging Research
- Endocrinology
Background:
- D-galactose is widely used to establish aging models.
- Aging is associated with male reproductive dysfunction, including decreased sperm count and altered hormone levels.
- Exendin-4 is a glucagon-like peptide-1 receptor agonist with potential therapeutic benefits.
Purpose of the Study:
- To investigate the protective effects of exendin-4 against D-galactose-induced reproductive system alterations in male mice.
- To evaluate exendin-4's impact on hormone levels, sperm count, and testicular morphology in an aging mouse model.
Main Methods:
- Male mice were divided into control, exendin-4, D-galactose, and D-galactose + exendin-4 groups.
- D-galactose was administered for six weeks to induce aging, with exendin-4 administered during the final 10 days.
- Reproductive parameters assessed included serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, sperm count, and testis morphology.
Main Results:
- D-galactose administration significantly decreased testis weight and volume, serum testosterone, and sperm count, while increasing LH and FSH levels.
- Exendin-4 treatment (1 and 10 nmol/kg) reversed these D-galactose-induced changes, improving testis parameters and sperm count.
- Exendin-4 (1 nmol/kg) also normalized LH and FSH levels and increased testosterone in both normal and aging mice.
Conclusions:
- D-galactose induces male reproductive aging via oxidative stress, leading to reduced sperm count and elevated LH/FSH.
- Exendin-4 effectively counteracts D-galactose-induced reproductive complications in an aging mouse model.
- Exendin-4 demonstrates potential as a therapeutic agent for age-related male reproductive decline.
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