Stringer Jessica, Groenewegen Ella, Liew Seng H, Hutt Karla
Ovarian Biology Laboratory, Biomedicine Discovery Institute, Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.
Reproduction. 2020 Feb;159(2):105-113. doi: 10.1530/REP-19-0337.
Primordial follicle oocytes are extremely vulnerable to DNA damage caused by exogenous agents, such as those commonly used to treat cancer. Consequently, female cancer patients often have diminished ovarian reserve, which if severe enough, can cause premature ovarian failure and early menopause. Advances in cancer therapies have resulted in significantly improved cancer survival rates; therefore, it is becoming increasingly important to devise strategies to protect the ovarian reserve from cancer treatments, to avoid loss of fertility and endocrine dysfunction. In this study, we aimed to determine whether supplementation with nicotinamide mononucleotide (NMN) could preserve the ovarian reserve following exposure to DNA-damaging cancer treatments. Adult female mice (n = 5-6/group) received saline or NMN (500 mg/kg/day) for 8 days. Mice were left untreated or exposed to γ-irradiation (0.1 Gy) or cyclophosphamide (150 mg/kg) on day 7 and ovaries and serum collected for analysis on day 12. We report that γ-irradiation treatment significantly reduced the number of primordial follicles, but supplementation with NMN did not prevent the observed follicle loss. Similarly, cyclophosphamide treatment significantly reduced primordial follicle numbers, but these losses were not prevented by NMN supplementation. In conclusion, depletion of the ovarian reserve following γ-irradiation or cyclophosphamide was not protected by NMN supplementation under the conditions employed in this study.
原始卵泡卵母细胞极易受到外源性因素（如常用于治疗癌症的药物）所导致的DNA损伤。因此，女性癌症患者的卵巢储备往往会减少，如果严重的话，会导致卵巢早衰和过早绝经。癌症治疗的进展显著提高了癌症生存率；因此，制定策略来保护卵巢储备免受癌症治疗的影响，以避免生育能力丧失和内分泌功能障碍变得越来越重要。在本研究中，我们旨在确定补充烟酰胺单核苷酸（NMN）是否能在暴露于具有DNA损伤作用的癌症治疗后保护卵巢储备。成年雌性小鼠（每组n = 5 - 6只）接受生理盐水或NMN（500 mg/kg/天）处理8天。在第7天，小鼠不进行处理或接受γ射线照射（0.1 Gy）或环磷酰胺（150 mg/kg），并在第12天收集卵巢和血清进行分析。我们报告，γ射线照射处理显著减少了原始卵泡的数量，但补充NMN并不能防止观察到的卵泡丢失。同样，环磷酰胺处理显著减少了原始卵泡数量，但补充NMN并不能防止这些损失。总之，在本研究采用的条件下，补充NMN并不能保护γ射线照射或环磷酰胺处理后卵巢储备的耗竭。
