| First Author | Uri-Belapolsky S | Year | 2014 |
| Journal | Proc Natl Acad Sci U S A | Volume | 111 |
| Issue | 34 | Pages | 12492-7 |
| PubMed ID | 25114230 | Mgi Jnum | J:214079 |
| Mgi Id | MGI:5588040 | Doi | 10.1073/pnas.1323955111 |
| Citation | Uri-Belapolsky S, et al. (2014) Interleukin-1 deficiency prolongs ovarian lifespan in mice. Proc Natl Acad Sci U S A 111(34):12492-7 |
| abstractText | 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-1alpha and IL-1beta-KO mice. IL-1alpha-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-1alpha-KO ovaries compared with WT ovaries. Serum anti-Mullerian hormone, a putative marker of ovarian reserve, was markedly higher in IL-1alpha-KO mice from 2.5 mo onward, along with a greater ovarian response to gonadotropins. IL-1beta-KO mice displayed a comparable but more subtle prolongation of ovarian lifespan compared with IL-1alpha-KO mice. The protein and mRNA of both IL-1alpha and IL-1beta 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-1beta, IL-6, and TNF-alpha in ovaries of IL-1alpha-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. |
