TY - JOUR
T1 - Morphological Evidence of 8-MOP-Induced Apoptosis in Rat Ovary
AU - McDermott, Danielle Cipolla
AU - Hoyer, Pat B.
AU - Diawara, Moussa M.
N1 - Funding Information:
We thank Dr. Kim Boekleheide of the Department of Pathology and Laboratory Medicine at Brown University for his technical advice during the study. This research was supported by the U.S. National Institutes of Health (NIGMS) SCORE grant 2S06 GM008197-20 MPRC-B and the Colorado State University-Pueblo Faculty Scholarly and ties grant.
PY - 2003
Y1 - 2003
N2 - 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.
AB - 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.
KW - Ovarian toxicity
KW - Psoralen skin photochemotherapy (PUVA)
KW - Xanthotoxin
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U2 - 10.1081/TXR-120026923
DO - 10.1081/TXR-120026923
M3 - Article
AN - SCOPUS:0347383942
SN - 0731-3837
VL - 22
SP - 701
EP - 708
JO - Journal of Toxicology - Toxin Reviews
JF - Journal of Toxicology - Toxin Reviews
IS - 4
ER -