title: Telomeres and human reproduction.
abstract: Telomeres mediate biologic aging in organisms as diverse as plants, yeast, and mammals. We propose a telomere theory of reproductive aging that posits telomere shortening in the female germ line as the primary driver of reproductive aging in women. Experimental shortening of telomeres in mice, which normally do not exhibit appreciable oocyte aging, and which have exceptionally long telomeres, recapitulates the aging phenotype of human oocytes. Telomere shortening in mice reduces synapsis and chiasmata, increases embryo fragmentation, cell cycle arrest, apoptosis, spindle dysmorphologies, and chromosome abnormalities. Telomeres are shorter in the oocytes from women undergoing in vitro fertilization, who then produce fragmented, aneuploid embryos that fail to implant. In contrast, the testes are replete with spermatogonia that can rejuvenate telomere reserves throughout the life of the man by expressing telomerase. Differences in telomere dynamics across the life span of men and women may have evolved because of the difference in the inherent risks of aging on reproduction between men and women. Additionally, growing evidence links altered telomere biology to endometriosis and gynecologic cancers, thus future studies should examine the role of telomeres in pathologies of the reproductive tract.
authors.affiliation: Department of Obstetrics and Gynecology, New York University, Langone Medical Center, New York City, New York.
authors.forename: Keri Horan
authors.initials: KH
authors.lastname: Kalmbach
authors.affiliation: Department of Obstetrics and Gynecology, New York University, Langone Medical Center, New York City, New York; Graduate Program in Pathology, Fluminense Federal University, Rio de Janeiro, and CAPES Foundation, Ministry of Education of Brazil, Brasilia, Brazil.
authors.forename: Danielle Mota
authors.initials: DM
authors.lastname: Fontes Antunes
authors.affiliation: Department of Obstetrics and Gynecology, New York University, Langone Medical Center, New York City, New York; São Paulo University, São Paulo, Brazil.
authors.forename: Roberta Caetano
authors.initials: RC
authors.lastname: Dracxler
authors.affiliation: Department of Obstetrics and Gynecology, New York University, Langone Medical Center, New York City, New York.
authors.forename: Taylor Warner
authors.initials: TW
authors.lastname: Knier
authors.affiliation: Department of Obstetrics and Gynecology, New York University, Langone Medical Center, New York City, New York.
authors.forename: Michelle Louise
authors.initials: ML
authors.lastname: Seth-Smith
authors.affiliation: Department of Obstetrics and Gynecology, New York University, Langone Medical Center, New York City, New York.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Nankai University, Tianjin, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, New York University, Langone Medical Center, New York City, New York. Electronic address: david.keefe@nyumc.org.
authors.forename: David Lawrence
authors.initials: DL
authors.lastname: Keefe
mesh_terms: D000818:Animals; D016922:Cellular Senescence / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D023421:Models, Animal; D009865:Oocytes / Q000502:physiology; D012098:Reproduction / Q000502:physiology*; D012727:Sex Characteristics; D013094:Spermatozoa / Q000502:physiology; D016615:Telomere / Q000502:physiology*; D059505:Telomere Homeostasis / Q000502:physiology*; D059506:Telomere Shortening / Q000502:physiology*