Ovarian Biology Laboratory, Biomedicine Discovery Institute, Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia.
Sci Rep. 2018 Apr 25;8(1):6516. doi: 10.1038/s41598-018-24960-5.
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.
达卡巴嗪常用于治疗生殖期女性常见的癌症。然而，达卡巴嗪对卵巢的非靶向作用的研究有限。我们评估了达卡巴嗪对原始卵泡卵巢储备的影响，原始卵泡对生育至关重要。8 周和 6 月龄 C57BL/6J 小鼠于第 0 天和第 7 天给予达卡巴嗪或生理盐水，然后分别于 12 小时（h）或 14 天（n=4-5/组）处死。计数卵泡数量、卵泡密度、血清 AMH 和黄体，并监测发情周期。在生殖期年轻小鼠中，达卡巴嗪在 12 小时内不影响原始卵泡数量，但在 14 天内导致原始卵泡减少 36%（p<0.05）。达卡巴嗪介导的原始卵泡耗竭随年龄而加速，在 12 小时和 14 天分别减少 24%（p<0.05）和 36%（p<0.01）。在任何年龄，治疗组之间的卵泡密度均无变化。达卡巴嗪在 14 天耗尽了窦前卵泡（p<0.05），在两个年龄组都是如此。尽管窦前卵泡部分减少，但血清 AMH、发情周期和黄体（排卵的标志）在两个年龄组之间的治疗组之间均无变化。重要的是，卵巢储备减少可导致卵巢早衰和不孕，因此，在达卡巴嗪治疗前，年轻女性患者应考虑选择生育力保存方案。
