Dacarbazine depletes the ovarian reserve in mice and depletion is enhanced with age

Amy L. Winship, Monika Bakai, Urooza Sarma, Seng H. Liew, Karla J. Hutt

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Dacarbazine is commonly administered for the treatment of cancers prevalent in reproductive age females. However, investigations of off-target effects of dacarbazine on the ovary are limited. We assessed the impact of dacarbazine on the ovarian reserve of primordial follicles, essential for fertility. Eight week and 6 month old C57BL/6 J mice were administered with dacarbazine or saline on day (d)0 and d7, then sacrificed after 12 hours (h), or 14d (n = 4-5/group). Follicle numbers, follicle density, serum AMH and corpora lutea were quantified and estrous cyclicity monitored. In reproductively young mice, dacarbazine did not affect primordial follicle numbers at 12 h, but resulted in a 36% reduction at 14d (p < 0.05). Dacarbazine-mediated primordial follicle depletion was accelerated with age, with a 24% (p < 0.05) and 36% (p < 0.01) reduction at 12 h and 14d. Follicle density remained unchanged between treatment groups at either age. Dacarbazine depleted antral follicles at 14d (p < 0.05), at both ages. Despite partial reduction of antral follicles, serum AMH, estrous cyclicity and corpora lutea (indicative of ovulation) remained unchanged between treatment groups, at both ages. Importantly, diminished ovarian reserve can result in premature ovarian insufficiency and infertility, thus, fertility preservation options should be considered for young female patients prior to dacarbazine treatment.

Original languageEnglish
Article number6516
Number of pages13
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 25 Apr 2018

Keywords

  • ageing
  • cell death

Cite this

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title = "Dacarbazine depletes the ovarian reserve in mice and depletion is enhanced with age",
abstract = "Dacarbazine is commonly administered for the treatment of cancers prevalent in reproductive age females. However, investigations of off-target effects of dacarbazine on the ovary are limited. We assessed the impact of dacarbazine on the ovarian reserve of primordial follicles, essential for fertility. Eight week and 6 month old C57BL/6 J mice were administered with dacarbazine or saline on day (d)0 and d7, then sacrificed after 12 hours (h), or 14d (n = 4-5/group). Follicle numbers, follicle density, serum AMH and corpora lutea were quantified and estrous cyclicity monitored. In reproductively young mice, dacarbazine did not affect primordial follicle numbers at 12 h, but resulted in a 36{\%} reduction at 14d (p < 0.05). Dacarbazine-mediated primordial follicle depletion was accelerated with age, with a 24{\%} (p < 0.05) and 36{\%} (p < 0.01) reduction at 12 h and 14d. Follicle density remained unchanged between treatment groups at either age. Dacarbazine depleted antral follicles at 14d (p < 0.05), at both ages. Despite partial reduction of antral follicles, serum AMH, estrous cyclicity and corpora lutea (indicative of ovulation) remained unchanged between treatment groups, at both ages. Importantly, diminished ovarian reserve can result in premature ovarian insufficiency and infertility, thus, fertility preservation options should be considered for young female patients prior to dacarbazine treatment.",
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Dacarbazine depletes the ovarian reserve in mice and depletion is enhanced with age. / Winship, Amy L.; Bakai, Monika; Sarma, Urooza; Liew, Seng H.; Hutt, Karla J.

In: Scientific Reports, Vol. 8, No. 1, 6516, 25.04.2018.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Dacarbazine depletes the ovarian reserve in mice and depletion is enhanced with age

AU - Winship, Amy L.

AU - Bakai, Monika

AU - Sarma, Urooza

AU - Liew, Seng H.

AU - Hutt, Karla J.

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