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2-Bromopropane causes ovarian dysfunction by damaging primordial follicles and their oocytes in female rats
1Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Abstract:
Ovarian dysfunction induced by 2-bromopropane (2-BP) has been described in female factory workers and experimental animals. However, the underlying mechanism is still unclear. To establish the reproductive target site and define mechanisms of 2-BP toxicity in adult female rats, we examined the effects of different doses and duration of exposure to 2-BP in female rats. In the dose-dependent experiments, female rats were exposed to 2-BP at 100, 300, or 1000 ppm or fresh air (n = 9 each) in exposure chambers for 8 h/day for 9 weeks. In the time-course experiments, female rats were exposed to 2-BP at 3000 ppm for 8 h (n = 7 each). The rats were then euthanized 1, 3, 5, and 17 days after exposure. Differential follicle counts and in situ terminal deoxynucleotidyl transferase assay were used to evaluate 2-BP effect on primordial, growing, and antral follicles. Exposure to 2-BP at 300 and 1000 ppm produced a significant reduction in the percentage of primordial, growing, and antral follicles in a dose-dependent manner. Significant reduction in the percentage of primordial follicles at 17 days after exposure was observed in time-course experiments. Exposure to 2-BP at 3000 ppm for 8 h resulted in histological changes in primordial follicles complex at 5 and 17 days after exposure. These changes consisted of distortion of the symmetry of oocytes and their nuclei at Day 5 after exposure and appearance of eccentric pyknotic cells and shrinkage of oocyte nuclei at Day 17 after exposure. In situ end labeling showed increased numbers of apoptotic oocytes and granulosa cells in primordial follicles at Days 5 and 17 after exposure. Our results suggested that ovarian dysfunction induced by 2-BP was caused by the destruction of primordial follicle and its oocyte due to the induction of apoptosis. Our studies also show that the follicle differential count is a more sensitive method than the vaginal smear in monitoring the female reproductive disorders induced by 2-BP.
Insights
2-bromopropane (2-BP) causes ovarian dysfunction by inducing apoptosis and destroying primordial follicles and oocytes in female rats. Follicle differential counts are more sensitive than vaginal smears for detecting 2-BP reproductive toxicity.
Area of Science:
- Reproductive Toxicology
- Environmental Health
- Cell Biology
Background:
- Ovarian dysfunction from 2-bromopropane (2-BP) is observed in humans and animals, but mechanisms remain unclear.
- Understanding 2-BP's reproductive toxicity is crucial for occupational safety and health.
- Identifying the specific target site and cellular mechanisms of 2-BP is essential.
Purpose of the Study:
- To determine the reproductive target site of 2-bromopropane (2-BP) in adult female rats.
- To elucidate the mechanisms underlying 2-BP-induced ovarian toxicity.
- To compare the sensitivity of follicle differential counts versus vaginal smears in monitoring 2-BP effects.
Main Methods:
- Dose-dependent exposure of female rats to 2-BP (100, 300, 1000 ppm) for 9 weeks.
- Time-course study with 2-BP (3000 ppm) exposure for 8 hours, followed by euthanasia at 1, 3, 5, and 17 days.
- Evaluation of follicle populations (primordial, growing, antral) using differential counts and apoptosis detection via in situ terminal deoxynucleotidyl transferase assay.
Main Results:
- 2-BP exposure significantly reduced primordial, growing, and antral follicles in a dose-dependent manner.
- Histological changes and apoptosis in oocytes and granulosa cells of primordial follicles were observed 5 and 17 days post-exposure.
- Follicle differential counts proved more sensitive than vaginal smears for detecting 2-BP-induced reproductive disorders.
Conclusions:
- 2-bromopropane induces ovarian dysfunction primarily through the destruction of primordial follicles and oocytes via apoptosis.
- The study identifies primordial follicles as a key target site for 2-BP toxicity.
- Follicle differential counting is a superior method for early detection of 2-BP-induced female reproductive toxicity.