Bertoldo Michael J, Rodriguez Paris Valentina, Gook Debra A, Edwards Melissa C, Wu Katherine, Liang Cai Jun Jean, Marinova Maria B, Wu Lindsay E, Walters Kirsty A, Gilchrist Robert B
Fertility and Research Centre, School of Women's and Children's Health, University of New South Wales Sydney, New South Wales, Australia.
Laboratory for Ageing Research, School of Medical Sciences, University of New South Wales Sydney, New South Wales, Australia.
Reproduction. 2021 Feb;161(2):215-226. doi: 10.1530/REP-20-0539.
Ovarian tissue cryopreservation and future transplantation is the only strategy to preserve the fertility of young female adolescent and prepubertal patients. The primary challenge to ovarian graft longevity is the substantial loss of primordial follicles during the period of ischaemia post-transplantation. Nicotinamide mononucleotide (NMN), a precursor of the essential metabolite NAD+, is known to reduce ischaemic damage. Therefore, the objective of the current study was to assess the impact of short- and long-term NMN administration on follicle number and health following ovarian tissue transplantation. Hemi-ovaries from C57Bl6 mice (n = 8-12/group) were transplanted under the kidney capsule of bilaterally ovariectomised severe combined immunodeficient (SCID) mice. Recipient mice were administered either normal drinking water or water supplemented with NMN (2 g/L) for either 14 or 56 days. At the end of each treatment period, ovarian transplants were collected. There was no effect of NMN on the resumption of oestrous or length of oestrous cycles. Transplantation significantly reduced the total number of follicles with the greatest impact observed at the primordial follicle stage. We report that NMN did not prevent this loss. While NMN did not significantly impact the proportion of apoptotic follicles, NMN normalised PCNA expression at the primordial and intermediate stages but not at later stages. In conclusion, NMN administration did not prevent ovarian follicle loss under the conditions of this study.
卵巢组织冷冻保存及后续移植是保留年轻女性青少年和青春期前患者生育能力的唯一策略。卵巢移植后长期存活面临的主要挑战是移植后缺血期间原始卵泡大量丢失。烟酰胺单核苷酸（NMN）是必需代谢物NAD+的前体，已知其可减少缺血损伤。因此，本研究的目的是评估短期和长期给予NMN对卵巢组织移植后卵泡数量和健康状况的影响。将C57Bl6小鼠的半卵巢（每组n = 8 - 12）移植到双侧卵巢切除的严重联合免疫缺陷（SCID）小鼠的肾包膜下。受体小鼠饮用正常饮用水或补充NMN（2 g/L）的水，持续14天或56天。在每个治疗期结束时，收集卵巢移植组织。NMN对发情恢复或发情周期长度没有影响。移植显著减少了卵泡总数，在原始卵泡阶段观察到的影响最大。我们报告NMN并不能阻止这种损失。虽然NMN对凋亡卵泡的比例没有显著影响，但NMN使原始卵泡和中间阶段的PCNA表达正常化，但后期阶段没有。总之，在本研究条件下，给予NMN并不能阻止卵巢卵泡的丢失。
