Department of Reproductive Medicine and Fertility Preservation, Hôpital Antoine Béclère, 92140 Clamart, France.
Inserm U1185 Université Paris-Sud, Université Paris Saclay, 94276 Le Kremlin Bicêtre, France.
Int J Mol Sci. 2019 Oct 27;20(21):5342. doi: 10.3390/ijms20215342.
Cancer treatment, such as chemotherapy, induces early ovarian follicular depletion and subsequent infertility. In order to protect gametes from the gonadotoxic effects of chemotherapy, several fertility preservation techniques-such as oocyte or embryo cryopreservation with or without ovarian stimulation, or cryopreservation of the ovarian cortex-should be considered. However, these methods may be difficult to perform, and the future use of cryopreserved germ cells remains uncertain. Therefore, improving the methods currently available and developing new strategies to preserve fertility represent major challenges in the area of oncofertility. Animal and ovarian culture models have been used to decipher the effects of different cytotoxic agents on ovarian function and several theories regarding chemotherapy gonadotoxicity have been raised. For example, cytotoxic agents might (i) have a direct detrimental effect on the DNA of primordial follicles constituting the ovarian reserve and induce apoptosis; (ii) induce a massive growth of dormant follicles, which are then destroyed; or (ii) induce vascular ovarian damage. Thanks to improvements in the understanding of the mechanisms involved, a large number of studies have been carried out to develop molecules limiting the negative impact of chemotherapy on the ovaries.
癌症治疗，如化疗，会导致早期卵泡耗竭和随后的不孕。为了保护配子免受化疗的性腺毒性作用，可以考虑几种生育力保存技术，如卵母细胞或胚胎冷冻保存，伴有或不伴有卵巢刺激，或卵巢皮质冷冻保存。然而，这些方法可能难以实施，并且冷冻保存的生殖细胞的未来使用仍然不确定。因此，改进现有的方法和开发新的策略来保存生育能力是肿瘤生育领域的主要挑战。动物和卵巢培养模型已被用于破译不同细胞毒性药物对卵巢功能的影响，并且已经提出了几种关于化疗性腺毒性的理论。例如，细胞毒性药物可能会：（i）直接对构成卵巢储备的原始卵泡的 DNA 造成损害，并诱导细胞凋亡；（ii）诱导休眠卵泡大量生长，然后将其破坏；或（iii）诱导血管性卵巢损伤。由于对相关机制的理解有所提高，已经进行了大量研究来开发分子，以限制化疗对卵巢的负面影响。
