Proinflammatory IL-1α Involvement in Premature Ovarian Failure: Impact On Fertility

Deanna Vuong

 Introduction: Premature Ovarian Failure (POF) is a disorder that affects a woman’s ovaries to function correctly prematurely before the age of 40. This disorder affects ~1% of the female population with an unknown etiology due to a multitude of factors. The main clinical manifestation is amenorrhea, accompanied by early menopausal symptoms such as hot flashes and loss of libido. Overall, POF lends to risk for osteoporosis, heart disease, and infertility. The female reproductive system is the first organ system to show overt signs of physiologic aging in humans. A study observed chronic inflammation in reproductively old mice.1 IL-1α is understudied despite its involvement during inflammation. 2  With IL-1α’s involvement in inflammation, researchers tested its role in age-related exhaustion of ovarian reserve and found increased IL-1α proteins expressed in ovaries as the mice age.3 There is currently no cure for POF, but with inflammation involved in POF, treatments involving bone-marrow derived mesenchymal cells are currently being researched. Methods: H&E staining on ovarian sections from 6-12 week old (young) and 14-17 month old (old) mice.Ovaries were collected from WT and IL-1α–KO female mice at progressively indicated ages and fixed in Bouin’s solution. WT and IL-1α–KO female mice were individually caged with a WT male for mating. Female mice were weighed before and after mating. Female mice that gained weight were considered pregnant and killed. Number of fetuses was recorded. Mice model POF by injection of cyclophosphamide. Ten mice were injected with BMMSCs, then sacrificed after 21 days for morphometric evaluation of the ovaries. Hormonal profile was evaluated. Another 10 mice were left for natural breeding with male mice, and 5 of these were injected with BMMSCs. Results: Multinucleated macrophage giant cells in ovarian stroma of reproductively old mice.1 IL-1α–KO mice showed a substantially higher pregnancy rate and litter size compared with WT mice at advanced age.3 Presence of newly formed primordial follicles. Contribution of MSCs to the formation of these follicles was proven by a labeling technique. The 5 mice that were injected with MSCs became pregnant after natural breeding.4 Conclusions: IL-1α involved in apoptotic and inflammatory pathogenesis of POF. BMMSCs have anti-oxidant and anti-inflammation properties that can heal ovarian damage. Option for those with POF-related infertility with unknown etiology. Replace current treatments with bad side effects such as HRT. Important for female cancer survivors that underwent chemo that destroyed their reproductive system.

 

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  3. Uri-Belapolsky S, Shaish A, Eliyahu E, et al. Interleukin-1 deficiency prolongs ovarian lifespan in mice. Proceedings of the National Academy of Sciences. 2014;111(34):12492-12497. doi:10.1073/pnas.1323955111.
  4. Badawy A, Sobh M, Ahdy M, Abdelhafez M. Bone marrow mesenchymal stem cell repair of cyclophosphamide-induced ovarian insufficiency in a mouse model. International Journal of Womens Health. 2017;Volume 9:441-447. doi:10.2147/ijwh.s13407.