Challenges and Potential for Ovarian Preservation with SERMs

Abstract

Tamoxifen (TAM) is a selective estrogen receptor modulator with tissue-specific effects on estrogen signaling used predominantly for treatment and chemoprevention of breast cancers. Recent studies have shown that TAM prevents infertility and decreases follicular loss from common cancer chemotherapy and radiation therapy in preclinical models. Here we review current and novel uses of selective estrogen receptor modulator s and advantages and challenges for translation of TAM for human fertility preservation.

Keywords: SERM; cancer; fertility; ovary; tamoxifen.

FIG. 1

A) Hematoxylin and eosin-stained sections of the ovary from rats exposed to vehicle (CONT), cyclophosphamide (Cy, 50 mg/wk), tamoxifen (TAM), or Cy + TAM for 2 wk. Arrowheads = primordial follicles; arrows = primary follicles. Cy decreased follicular reserves compared to CONT, and the addition of TAM inhibited this depletion. TAM alone elevated the number of follicles compared to CONT. Bar = 50 μm. B) Numbers of primordial follicle loss relative to CONT. Average number of follicles per ovary in CONT was 6.1 × 10³. Cy at 35 and 50 mg/kg/wk induced follicles loss compared to CONT, and the addition of TAM to both doses of Cy inhibited this depletion. TAM alone did not affect follicle numbers. Different letters indicate significant differences among different treatment groups. Adapted from Ting and Petroff (2010) [1] with permission.

FIG. 2

A) Mature rat oocytes exposed to vehicle (CONT), 4-hydroxytamoxifen (4HT), doxorubicin (DOX), or DOX+4HT for 26 h. Healthy oocytes surrounded by zona pellucida were observed after CONT and 4HT treatment. DOX induces fragmentation in cultured oocytes, an effect that is antagonized by the addition of 4HT. Original magnification ×400. B) Percentage of oocytes undergoing fragmentation. Oocytes incubated with DOX showed increased fragmentation rate compared with CONT. This elevated fragmentation rate was inhibited by the addition of 4HT. The total number of oocytes cultured in each treatment group is indicated in parentheses inside the respective bar. The asterisk (*) indicates a significant difference in comparison to CONT. Adapted from Ting and Petroff (2010) [1] with permission.