title: Interleukin-1 deficiency prolongs ovarian lifespan in mice.
abstract: Oocyte endowment dwindles away during prepubertal and adult life until menopause occurs, and apoptosis has been identified as a central mechanism responsible for oocyte elimination. A few recent reports suggest that uncontrolled inflammation may adversely affect ovarian reserve. We tested the possible role of the proinflammatory cytokine IL-1 in the age-related exhaustion of ovarian reserve using IL-1α and IL-1β-KO mice. IL-1α-KO mice showed a substantially higher pregnancy rate and litter size compared with WT mice at advanced age. The number of secondary and antral follicles was significantly higher in 2.5-mo-old IL-1α-KO ovaries compared with WT ovaries. Serum anti-Müllerian hormone, a putative marker of ovarian reserve, was markedly higher in IL-1α-KO mice from 2.5 mo onward, along with a greater ovarian response to gonadotropins. IL-1β-KO mice displayed a comparable but more subtle prolongation of ovarian lifespan compared with IL-1α-KO mice. The protein and mRNA of both IL-1α and IL-1β mice were localized within the developing follicles (oocytes and granulosa cells), and their ovarian mRNA levels increased with age. Molecular analysis revealed decreased apoptotic signaling [higher B-cell lymphoma 2 (BCL-2) and lower BCL-2-associated X protein levels], along with a marked attenuation in the expression of genes coding for the proinflammatory cytokines IL-1β, IL-6, and TNF-α in ovaries of IL-1α-KO mice compared with WT mice. Taken together, IL-1 emerges as an important participant in the age-related exhaustion of ovarian reserve in mice, possibly by enhancing the expression of inflammatory genes and promoting apoptotic pathways.
authors.affiliation: The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel-Hashomer 52621, Israel; Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel; and.
authors.forename: Shiri
authors.initials: S
authors.lastname: Uri-Belapolsky
authors.affiliation: The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel-Hashomer 52621, Israel;
authors.forename: Aviv
authors.initials: A
authors.lastname: Shaish
authors.affiliation: Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sin, New York, NY 10029.
authors.forename: Efrat
authors.initials: E
authors.lastname: Eliyahu
authors.affiliation: Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel; and.
authors.forename: Hadas
authors.initials: H
authors.lastname: Grossman
authors.affiliation: Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel; and.
authors.forename: Mattan
authors.initials: M
authors.lastname: Levi
authors.affiliation: Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel; and.
authors.forename: Dana
authors.initials: D
authors.lastname: Chuderland
authors.affiliation: Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel; and.
authors.forename: Lihi
authors.initials: L
authors.lastname: Ninio-Many
authors.affiliation: Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel; and.
authors.forename: Noa
authors.initials: N
authors.lastname: Hasky
authors.affiliation: The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel-Hashomer 52621, Israel;
authors.forename: David
authors.initials: D
authors.lastname: Shashar
authors.affiliation: The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel-Hashomer 52621, Israel;
authors.forename: Tal
authors.initials: T
authors.lastname: Almog
authors.affiliation: The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel-Hashomer 52621, Israel;
authors.forename: Michal
authors.initials: M
authors.lastname: Kandel-Kfir
authors.affiliation: The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel-Hashomer 52621, Israel;
authors.forename: Dror
authors.initials: D
authors.lastname: Harats
authors.affiliation: Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel; and.
authors.forename: Ruth
authors.initials: R
authors.lastname: Shalgi
authors.affiliation: The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel-Hashomer 52621, Israel; yehuda.kamari@sheba.health.gov.il.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Kamari
mesh_terms: D000375:Aging; D000818:Animals; D054304:Anti-Mullerian Hormone / Q000097:blood; D017209:Apoptosis; D005260:Female; D015870:Gene Expression; D018836:Inflammation Mediators / Q000378:metabolism; D053582:Interleukin-1alpha / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D053583:Interleukin-1beta / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D008098:Litter Size; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010053:Ovary / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011962:Receptors, FSH / Q000235:genetics / Q000502:physiology; D053573:Receptors, Interleukin-1 Type I / Q000172:deficiency / Q000235:genetics / Q000502:physiology
chemical_list: C583355:IL1R1 protein, mouse; D018836:Inflammation Mediators; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D012333:RNA, Messenger; D011962:Receptors, FSH; D053573:Receptors, Interleukin-1 Type I; D054304:Anti-Mullerian Hormone
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