Prenatal metformin treatment improves ovarian function in offspring of obese rats

Area of Science:

• Reproductive biology
• Developmental origins of health and disease
• Pharmacology

Background:

• Maternal obesity is linked to offspring metabolic and reproductive issues.
• Obese mothers' female offspring exhibit elevated serum estradiol and polycystic ovary syndrome (PCOS)-like conditions.
• Decreased hepatic cytochrome P450 3A2 levels in offspring may contribute to elevated estradiol.

Purpose of the Study:

• To investigate if metformin administration to obese mothers can prevent reproductive dysfunction in female offspring.
• To examine metformin's effects on serum estradiol, hepatic cytochrome P450 3A2, ovarian follicle development, and ovarian sympathetic activity.

Main Methods:

• Obese rats were treated with metformin during pregnancy and nursing.
• Offspring serum estradiol, hepatic cytochrome P450 3A2 levels, and ovarian morphology were assessed.
• Ovarian norepinephrine and 3-methoxy-4-hydroxyphenylglycol levels were measured to evaluate sympathetic activity.

Main Results:

• Metformin prevented increased serum estradiol and restored hepatic cytochrome P450 3A2 levels in offspring.
• While metformin did not prevent advanced puberty, it normalized antral follicle counts, reduced follicular cysts, and decreased multi-oocyte follicles.
• Metformin administration prevented increased ovarian norepinephrine and 3-methoxy-4-hydroxyphenylglycol levels, indicating reduced sympathetic activity.

Conclusions:

• Metformin partially prevents maternal obesity-induced ovarian dysfunction in female offspring.
• Metformin's protective effects involve restoring hormonal balance and mitigating increased ovarian sympathetic activity.
• This study highlights metformin's potential as a therapeutic intervention for offspring of obese mothers.