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

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 fertilit...

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Autores principales: Winship, Amy L., Bakai, Monika, Sarma, Urooza, Liew, Seng H., Hutt, Karla J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5917018/
https://www.ncbi.nlm.nih.gov/pubmed/29695822
http://dx.doi.org/10.1038/s41598-018-24960-5
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author Winship, Amy L.
Bakai, Monika
Sarma, Urooza
Liew, Seng H.
Hutt, Karla J.
author_facet Winship, Amy L.
Bakai, Monika
Sarma, Urooza
Liew, Seng H.
Hutt, Karla J.
author_sort Winship, Amy L.
collection PubMed
description 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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spelling pubmed-59170182018-04-30 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. Sci Rep Article 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. Nature Publishing Group UK 2018-04-25 /pmc/articles/PMC5917018/ /pubmed/29695822 http://dx.doi.org/10.1038/s41598-018-24960-5 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Winship, Amy L.
Bakai, Monika
Sarma, Urooza
Liew, Seng H.
Hutt, Karla J.
Dacarbazine depletes the ovarian reserve in mice and depletion is enhanced with age
title Dacarbazine depletes the ovarian reserve in mice and depletion is enhanced with age
title_full Dacarbazine depletes the ovarian reserve in mice and depletion is enhanced with age
title_fullStr Dacarbazine depletes the ovarian reserve in mice and depletion is enhanced with age
title_full_unstemmed Dacarbazine depletes the ovarian reserve in mice and depletion is enhanced with age
title_short Dacarbazine depletes the ovarian reserve in mice and depletion is enhanced with age
title_sort dacarbazine depletes the ovarian reserve in mice and depletion is enhanced with age
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5917018/
https://www.ncbi.nlm.nih.gov/pubmed/29695822
http://dx.doi.org/10.1038/s41598-018-24960-5
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