title: Systemic signals in aged males exert potent rejuvenating effects on the ovarian follicle reserve in mammalian females.
abstract: Through the use of parabiosis in mice, aging-related deterioration of skeletal muscle and liver has been linked to a loss of systemic factors that support adult stem or progenitor cell activity. Since aging-related ovarian failure has recently been attributed, at least in part, to a loss of de-novo oocyte-containing follicle formation associated with declining oogonial stem cell activity, herein we tested in mice if aging-related changes in systemic factors influence the size of the ovarian follicle reserve. Ovaries of young (2-month-old) females parabiotically joined with young females for 5 weeks possess comparable numbers of healthy and degenerative (atretic) oocyte-containing follicles in their ovaries as those detected in non-parabiotic young females. Joining of young females with young males significantly increases follicle atresia without a net change healthy follicle numbers. Surprisingly, young females joined with aged (24-month-old) males exhibit a significant increase in the number of primordial follicles comprising the ovarian reserve, and this occurs without changes in follicle growth activation or atresia. Blood of aged males also induces ovarian expression of the germ cell-specific meiosis gene,Stimulated by retinoic acid gene 8 (Stra8), in ovaries of female parabionts, further supporting the conclusion that the observed changes in the follicle reserve of females joined with aged males reflect increased oocyte formation. Thus, factors in male blood exert dramatic effects on ovarian follicle dynamics, and aging males possess a beneficial systemic factor that significantly expands the ovarian follicle reserve in females through enhanced oogenesis.
authors.affiliation: Vincent Center for Reproductive Biology, Vincent Department of Obstetrics and Gynecology, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Niikura
authors.forename: Teruko
authors.initials: T
authors.lastname: Niikura
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Chonthicha
authors.initials: C
authors.lastname: Satirapod
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Tilly
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000818:Animals; D005260:Female; D005496:Follicular Atresia; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009866:Oogenesis; D006080:Ovarian Follicle / Q000254:growth & development / Q000378:metabolism*; D010227:Parabiosis; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012060:Rejuvenation; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C508515:DAZL protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C102019:Stra8 protein, mouse