Tamoxifen decreases ovarian follicular loss from experimental toxicant DMBA and chemotherapy agents cyclophosphamide and doxorubicin in the rat

Alison Ting, Brian K. Petroff

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Introduction 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.

Original languageEnglish (US)
Pages (from-to)591-597
Number of pages7
JournalJournal of Assisted Reproduction and Genetics
Volume27
Issue number11
DOIs
StatePublished - Nov 2010
Externally publishedYes

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9,10-Dimethyl-1,2-benzanthracene
Tamoxifen
Doxorubicin
Cyclophosphamide
Drug Therapy
Ovarian Follicle
Oocytes
Fertility
Fertility Preservation
Litter Size
Pharmaceutical Preparations
Carcinogens
Neoplasms
Survival

Keywords

  • Cancer
  • Chemotherapy
  • Ovary
  • Rat
  • Toxicology

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Reproductive Medicine
  • Developmental Biology
  • Genetics
  • Genetics(clinical)

Cite this

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abstract = "Introduction 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.",
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AU - Petroff, Brian K.

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N2 - Introduction 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.

AB - Introduction 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.

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KW - Toxicology

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