Morphological Evidence of 8‐MOP‐Induced Apoptosis in Rat Ovary

Psoralens have been shown to cause reproductive toxicity in both male and female rats. Recent research demonstrated that exposure to 8‐methoxypsoralen (or xanthotoxin) decreases 17‐β estradiol and aromatase translation in the ovary of Wistar rats. We initiated the present study to determine whether morphological evidence of apoptotic damage exists with xanthotoxin treatment. Female Wistar rats were dosed with xanthotoxin (180 mg/kg, p.o.) or the control vehicle for 30 days. Animals were then sacrificed and ovaries were removed, fixed and serially sectioned for histological examination. Ovaries from xanthotoxin‐dosed females revealed characteristics of extensive apoptotic damage not evident in control follicles. Follicles from these xanthotoxin‐treated rats displayed such characteristics of apoptosis as pyknotic nuclei in the antrum, detachment of the follicular membrane from the theca interna, and dissolution of the corona radiata. The present study provides visual evidence of xanthotoxin‐induced apoptotic damage, typical of exposure to high levels of reactive oxygen species. This proposed mechanism of follicular apoptosis is consistent with previously reported xanthotoxin‐induced reduction in circulating 17β‐estradiol levels, reduced transcription of cytochrome P450 aromatase, and an increased DNA fragmentation.