Related Experiment Videos
Ovarian toxicity of benzo(a)pyrene and metabolites in mice
D R Mattison1, H Singh, K Takizawa
1Department of Obstetrics and Gynecology, University of Arkansas for Medical Sciences, Little Rock.
Abstract:
The effect of intraovarian injection of benzo(a)pyrene (BP) or one of three metabolites: +7,8-oxide (7,8-O), (-)-dihydrodiol (DHD), and (+)-diol-epoxide-2 (DE2) on ovarian volume, weight, and follicle number was investigated in DBA/2N (D2), C57BL/6N (B6), and (DBA/2N x C57BL/6N)F1 (F1) mice. Female mice, 6 to 8 weeks old, were treated by injection into the right ovary with the indicated compound (10 micrograms in 1 microL DMSO). The left ovary was untreated. Two weeks following treatment both ovaries were removed, fixed in Bouin's medium, serially sectioned, and stained with hematoxylin and eosin. Right ovarian weight was decreased in D2 mice treated with BP (P less than 0.01 and DHD (P less than 0.01). Left ovarian weight was increased in D2 mice treated with DE2 (P less than 0.05). BP decreased right ovarian volume in D2 (P less than 0.01) and F1 (P less than 0.01) mice. 7,8-O decreased right ovarian volume in D2 mice (P less than 0.05). DHD decreased right ovarian volume in D2 (P less than 0.01) and F1 (P less than 0.05) mice. DE2 decreased right ovarian volume in D2 (P less than 0.01) and F1 (P less than 0.01) mice. Left ovarian volume was increased in B6 (P less than 0.01) and D2 (P less than 0.05) mice treated with DE2. The number of small follicles was decreased in D2, B6, and F1 mice treated with DE2 (P less than 0.01). BP and DHD also decreased small follicle number in D2 and F1 mice (P less than 0.01). The number of growing follicles was decreased in B6, D2, and F1 mice treated with DE2 (P less than 0.01). Treatment with DHD decreased the number of growing follicles in D2 mice (P less than 0.05). The number of antral follicles was reduced in F1 mice treated with BP (P less than 0.05), DHD (P less than 0.01), and DE2 (P less than 0.01). The number of antral follicles was also reduced in B6 mice treated with DE2 (P less than 0.01) and in D2 mice treated with DHD (P less than 0.05) and D2 mice treated with DE2 (P less than 0.01). These experiments suggest that toxic effects to one ovary may result in compensatory hypertrophy of the contralateral ovary. Morphometric analysis of the ovary, including ovarian volume, represents a useful objective measure of ovarian toxicity.
Insights
Benzo(a)pyrene and its metabolites induce ovarian toxicity, decreasing ovarian volume and follicle counts in mice. Toxic effects on one ovary may lead to compensatory hypertrophy of the other ovary.
Area of Science:
- Toxicology
- Reproductive Biology
- Environmental Health
Background:
- Benzo(a)pyrene (BP) is a polycyclic aromatic hydrocarbon found in the environment.
- BP and its metabolites can exert toxic effects on various organs, including reproductive systems.
- Understanding the specific impact of BP metabolites on ovarian function is crucial for assessing reproductive risks.
Purpose of the Study:
- To investigate the effects of intraovarian injection of benzo(a)pyrene (BP) and its metabolites on ovarian morphology and follicle counts in different mouse strains.
- To determine if toxic effects on one ovary can induce compensatory changes in the contralateral ovary.
- To evaluate morphometric analysis as an objective measure of ovarian toxicity.
Main Methods:
- Intraovarian injection of BP or its metabolites (+7,8-oxide, (-)-dihydrodiol, (+)-diol-epoxide-2) into the right ovary of DBA/2N, C57BL/6N, and F1 hybrid mice.
- Assessment of ovarian weight, volume, and follicle numbers (small, growing, antral) two weeks post-injection.
- Histological examination of ovarian tissues stained with hematoxylin and eosin.
Main Results:
- BP and DHD significantly decreased right ovarian weight and volume in DBA/2N mice.
- DE2 treatment led to increased left ovarian weight and volume in DBA/2N and B6 mice, suggesting compensatory hypertrophy.
- BP metabolites significantly reduced the number of small, growing, and antral follicles across all mouse strains, indicating widespread ovarian toxicity.
Conclusions:
- Intraovarian exposure to BP and its metabolites causes significant ovarian toxicity, characterized by reduced ovarian size and diminished follicle populations.
- The contralateral ovary may exhibit compensatory hypertrophy in response to unilateral ovarian toxicity.
- Ovarian morphometric analysis, including volume and weight, serves as a reliable indicator of chemical-induced ovarian toxicity.