Tamoxifen decreases ovarian follicular loss from experimental toxicant DMBA and chemotherapy agents cyclophosphamide and doxorubicin in the rat.
BACKGROUND
we serendipitously observed a protective effect of tamoxifen against depletion of ovarian follicles by 7,12-dimethylbenzanthracene (DMBA), a chemical carcinogen, during a cancer prevention study. Such ovarian protection is being sought as an alternative approach to fertility preservation in human cancer patients.


METHODS
rats received tamoxifen (0, 1 mg or 2.5 mg/kg/d) and DMBA (0, 1, 2 mg/kg/wk) or cyclophosphamide (0, 35, 50 mg/kg/wk). Ovarian follicles were quantified and effects on fertility and litter size were tested. Cultured oocytes were exposed to chemotherapy drug doxorubicin, with or without 4-hydroxytamoxifen (4HT).


RESULTS
DMBA and cyclophosphamide decreased the number of primordial and total follicles, and this reduction was prevented by tamoxifen. Cyclophosphamide tended to reduce fertility and lessened neonatal survival. Tamoxifen reversed these defects. Doxorubicin caused oocyte fragmentation which was prevented by 4HT.


CONCLUSIONS
tamoxifen decreases follicle loss and improves reproductive function following exposure to ovarian toxicants including chemotherapy drugs in the female rat.
Ting
Alison Y
AY
Breast Cancer Prevention Center, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Petroff
Brian K
BK
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000633:toxicity*; D004317:Doxorubicin / Q000633:toxicity*; D005260:Female; D005298:Fertility / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects; D006080:Ovarian Follicle / Q000187:drug effects*; D010053:Ovary / Q000187:drug effects / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology*
D000970:Antineoplastic Agents; D020011:Protective Agents; D013629:Tamoxifen; C016601:afimoxifene; D015127:9,10-Dimethyl-1,2-benzanthracene; D004317:Doxorubicin; D003520:Cyclophosphamide