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

  • Fertility Preservation
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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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Author information

Authors and Affiliations

  1. Breast Cancer Prevention Center, University of Kansas Medical Center, Kansas City, KS, 66160, USA

    Alison Y. Ting & Brian K. Petroff

  2. Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, 66160, USA

    Alison Y. Ting

  3. Department of Internal Medicine, University of Kansas Medical Center, 3901 Rainbow Blvd., Mail Stop 3003, Kansas City, KS, 66160, USA

    Brian K. Petroff

  4. Center for Reproductive Sciences, University of Kansas Medical Center, Kansas City, KS, 66160, USA

    Brian K. Petroff

Authors
  1. Alison Y. Ting
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  2. Brian K. Petroff
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Correspondence to Brian K. Petroff.

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Tamoxifen decreases follicle loss and improves reproductive function following exposure to ovarian toxicants, including chemotherapy drugs, in the female rat.

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Ting, A.Y., Petroff, B.K. Tamoxifen decreases ovarian follicular loss from experimental toxicant DMBA and chemotherapy agents cyclophosphamide and doxorubicin in the rat. J Assist Reprod Genet 27, 591–597 (2010). https://doi.org/10.1007/s10815-010-9463-y

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  • DOI: https://doi.org/10.1007/s10815-010-9463-y

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