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Long-term ovarian and gonadotropin changes in mice exposed to 4-vinylcyclohexene
S B Hooser1, D P Douds, D G DeMerell
1Department of Pharmacology and Toxicology, University of Arizona, College of Pharmacy, Tucson 85721.
Abstract:
This study investigated the relationships between 4-vinylcyclohexene-induced follicular destruction, plasma FSH levels, and the development of ovarian preneoplastic changes. Female, 28-day-old, B6C3F1 mice were administered VCH (800 mg/kg/day, ip) or sesame seed oil, ip daily for 30 days. At 30, 60, 120, 240, and 360 days following the beginning of treatment, groups were killed, their ovaries were harvested, and plasma was collected for measurement of FSH. Ovarian weight was less and oocytes contained in preantral follicles were significantly fewer than controls at all time points. Plasma FSH concentrations in VCH-treated animals were increased significantly above controls at 240 d and 360 d. Histologically, there was oocyte loss at all times, whereas at 240 and 360 days, small to medium, irregularly shaped foci of hypertrophic cells were present. In addition, at 360 days 80% of the VCH-treated mice had a 1- to 2-mm, blood-filled cystic structure present in one or both ovaries. These studies indicate that VCH-induced oocyte destruction and follicle loss are associated with increases in plasma FSH, are associated with ovarian failure at 360 days, and are temporally related to ovarian cellular hypertrophy and the formation of blood-filled cystic ovarian structures. These events are possibly related to ovarian neoplasms produced by long-term exposure to VCH.
Insights
Exposure to 4-vinylcyclohexene (VCH) causes ovarian damage and follicle loss in mice. This damage is linked to increased plasma FSH levels and the development of ovarian cysts, potentially leading to neoplasms.
Area of Science:
- Reproductive Toxicology
- Ovarian Physiology
- Endocrinology
Background:
- 4-vinylcyclohexene (VCH) is a chemical known to induce ovarian toxicity.
- Understanding the relationship between VCH exposure, hormonal changes, and ovarian pathologies is crucial for reproductive health.
- Follicular destruction and subsequent hormonal imbalances can lead to long-term ovarian dysfunction.
Purpose of the Study:
- To investigate the effects of VCH on ovarian follicular destruction.
- To examine the association between VCH-induced ovarian changes and plasma follicle-stimulating hormone (FSH) levels.
- To determine the temporal relationship between VCH exposure and the development of ovarian preneoplastic lesions.
Main Methods:
- Female B6C3F1 mice were administered VCH (800 mg/kg/day) or a control (sesame seed oil) daily for 30 days.
- Ovarian and plasma samples were collected at multiple time points (30, 60, 120, 240, 360 days post-treatment).
- Ovarian weight, oocyte counts, plasma FSH levels, and histological changes were analyzed.
Main Results:
- VCH treatment significantly reduced ovarian weight and the number of oocytes in preantral follicles.
- Plasma FSH levels were significantly elevated in VCH-treated mice at 240 and 360 days.
- Histological analysis revealed progressive oocyte loss, ovarian cellular hypertrophy, and the formation of blood-filled cystic structures in VCH-exposed mice.
Conclusions:
- VCH-induced oocyte and follicle loss are associated with elevated plasma FSH levels.
- The observed ovarian changes, including cellular hypertrophy and cyst formation, are temporally related to VCH exposure.
- These findings suggest a potential link between long-term VCH exposure and the development of ovarian neoplasms.