Young adult donor bone marrow infusions into female mice postpone age-related reproductive failure and improve offspring survival.
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.
Selesniemi
Kaisa
K
Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114, USA.
Lee
Ho-Joon
HJ
Niikura
Teruko
T
Tilly
Jonathan L
JL
D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000502:physiology*; D046528:Chimerism; D005260:Female; D005298:Fertility / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008098:Litter Size; D008297:Male; D008423:Maternal Age; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009026:Mortality; D010053:Ovary / Q000166:cytology; D011247:Pregnancy; D012098:Reproduction / Q000502:physiology*; D015996:Survival Rate
C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins