Exposure to low doses of 3-methylcholanthrene impacts on the oocyte integrity without causing systemic cytotoxicity

ALICIA GRACIELA FALETTI; GALARZA, ROCÍO ALEJANDRA; ERIC ALEJANDRO RHON CALDERON

Honolulu, Hawaii

Congreso; 15th International Congress of Toxicology (IUTOX 2019); 2019

International Society of Toxicology

Previously, we showed that daily exposure to 3-methylcholathrene (3MC), a polyaromatichydrocarbon, at 0.1-1.0 mg/kg, alters the ovarian function by affecting follicle growth and ovulation in parallel with DNA damage in bone marrow cells and oocytes. Thus, the aim of this work was to study the effects of non-daily exposure to 3MC (lower doses than in our previous work) at gonadal and systemic level and the ability of α-naphthoflavone (αNF) to prevent this action. To this end, immature rats were exposed to a combination of 3MC 0.1 mg/kg and αNF 80 mg/kg three times a week, for three weeks. Follicular growth was examined by histology, oocyte integrity by morphological parameters, oocyte viability by fluorescent dyes, meiotic spindle by immunostaining, and apoptosis by the TUNEL assay. Compared with control animals (C), 3MC exposure i) decreased the percentage of immature and antral follicles (15-25%, P<0.05), the ovulation rate, expressed as the number of oocytes within oviducts (C 13.7±0.3; 3MC 11.1±0.4, P<0.01) and the percentage ofhealth oocytes (C 86±2; 3MC 76±1; P<0.01); ii) increased the oocyte area, expressed as μm2 (C 12.1±0.2; 3MC 12.7±0.1), the perimeter expressed as μm (C 79±1; 3MC 85±2; P<0.01), and the perivitelline space expressed as μm (C 1.57±0.08; 3MC 1.94±0.03; P<0.01); iii) decreased the thickness of the zona pellucida expressed as μm (C 1.7±0.1; 3MC 1.5±0.1; P<0.01), the percentage of oocytes with normal meiotic spindle (C 97±1; 3MC 91±1; P<0.01); and iv) increased the number of apoptotic follicles (C 3.6±0.2; 3MC 4.8±0.3; P<0.05). All these changes were prevented by the cotreatment with αNF. In addition, this 3MC exposure caused DNA damage in oocytes, but not in peripheral blood or bone marrow cells. In conclusion, exposure to low doses of 3MC was able to destroy the follicular pool, alter the oocyte integrity, and induce apoptosis, while αNF prevented all3MC-induced toxic effects. It is worthy to note that 3MC, at low doses, may be a potent ovotoxicant without causing systemic toxicity.