Selesniemi Kaisa, Lee Ho-Joon, Niikura Teruko, Tilly Jonathan L
Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114, USA.
Aging (Albany NY). 2008 Nov 14;1(1):49-57. doi: 10.18632/aging.100002.
The female reproductive axis is the first major organ system of the body to fail with advancing age. In addition to a permanent cessation of fertile potential, the loss of cyclic ovarian function in humans heralds the onset of menopause, which in turn underlies the emergence of a diverse spectrum of health issues in aging women. Recently, it was reported that bone marrow (BM) transplantation (BMT) into adult female mice conditioned a week earlier with highly cytotoxic drugs rescues ovarian function and fertility. Herein we show in mice receiving no prior conditioning regimen that once-monthly infusions of BM-derived cells retrieved from young adult female donors bearing an enhanced green fluorescent protein (EGFP) transgene sustain the fertile potential of aging wild-type females long past their time of normal reproductive senescence. The fertility-promoting effects of female donor BM are observed regardless whether the infusions are initiated in young adult or middle-aged females. Although the mechanism by which BM infusions benefit the reproductive performance of aging females remains to be elucidated, the absence of EGFP-expressing offspring suggests that it does not depend on development of mature eggs derived from germline-committed cells in the donor marrow. However, donor BM-derived somatic cells accumulate in the recipients, indicating efficient donor cell engraftment without prior conditioning. These findings provide a strong impetus to further explore development of adult stem cell-based technologies to safely extend function of the female reproductive axis into advanced age without the need for toxic pre-conditioning protocols routinely used in other models of stem cell delivery.
女性生殖轴是身体中随年龄增长而最先出现功能衰退的主要器官系统。除了生育能力永久丧失外，人类卵巢周期性功能的丧失预示着更年期的开始，而更年期又成为老年女性出现各种健康问题的根源。最近有报道称，对成年雌性小鼠进行一周前的高细胞毒性药物预处理后进行骨髓（BM）移植，可挽救卵巢功能和生育能力。在此我们表明，在未接受任何预处理方案的小鼠中，每月一次输注从携带增强型绿色荧光蛋白（EGFP）转基因的年轻成年雌性供体中获取的骨髓来源细胞，可使衰老的野生型雌性小鼠在正常生殖衰老时间之后很长一段时间内维持生育能力。无论输注是在年轻成年雌性还是中年雌性中开始，均可观察到雌性供体骨髓的促生育作用。尽管骨髓输注有益于衰老雌性小鼠生殖性能的机制仍有待阐明，但未出现表达EGFP的后代表明，这并不依赖于供体骨髓中生殖系定向细胞产生的成熟卵子的发育。然而，供体骨髓来源的体细胞在受体中积累，表明无需预处理即可实现高效的供体细胞植入。这些发现为进一步探索基于成体干细胞的技术发展提供了强大动力，以安全地将女性生殖轴的功能延长至高龄，而无需在其他干细胞递送模型中常规使用的有毒预处理方案。
