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-1? and IL-1?-KO mice. IL-1?-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-1?-KO ovaries compared with WT ovaries. Serum anti-Müllerian hormone, a putative marker of ovarian reserve, was markedly higher in IL-1?-KO mice from 2.5 mo onward, along with a greater ovarian response to gonadotropins. IL-1?-KO mice displayed a comparable but more subtle prolongation of ovarian lifespan compared with IL-1?-KO mice. The protein and mRNA of both IL-1? and IL-1? 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-1?, IL-6, and TNF-? in ovaries of IL-1?-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.

SUBMITTER: Uri-Belapolsky S 

PROVIDER: S-EPMC4151745 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature