The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

The ovarian follicle reserve is preserved in inflammasome-deficient mice (#56)

Carolina Lliberos Requesens 1 , Seng H Liew 1 , Ashley Mansell 2 , Steve Gerondakis 3 , Karla Hutt 1
  1. Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia
  2. Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, Australia
  3. Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia

Ovarian ageing is defined by a progressive decline in oocyte/follicle number and quality, leading to loss of fertility and ovarian function, cycle irregularity and eventually menopause. The factors that contribute to the depletion of follicles throughout reproductive life are poorly characterised. However, with more women delaying childbearing beyond the age of 35 years, there is a growing need to elucidate the mechanisms underlying the reproductive ageing process. Several recent studies have shown that low level chronic inflammation, driven by the NLRP3 inflammasome, is associated with normal and pathological ageing in many organ systems. Notably, mice lacking key components of the NLRP3 inflammasome, ASC or NRLP3, live for longer and exhibit a delayed ageing phenotype compared to wild type (WT) mice. Therefore, in this study we investigated the hypothesis that inflammatory processes contribute to ovarian ageing by comparing follicle numbers in WT mice with age-matched asc-/- and nlrp3-/- mice (n=3-4/genotype). At 12 months of age, WT mice were nearing the end of their reproductive lifespan and had significantly depleted primordial follicle reserves, consistent with ovarian ageing. In striking contrast, the primordial follicle reserves remained extremely high in asc-/- mice (WT= 229±32 vs asc-/-= 824±96, p<0.0001). Primordial follicle numbers were also significantly elevated in nlrp3-/- mice, though to a lesser extent (WT= 229±32 vs nlrp3-/-= 399±41, p=0.0194). The number of primary and secondary follicles did not show any statistically significant differences. However, the number of antral follicles was also significantly higher in 12 months old inflammation-deficient mice compared with WT (WT= 14±3 vs asc-/-= 36±6, p=0.017;  vs nlrp3-/-= 33±3,  p=0.0044). These findings suggest that the inflammation, and the NRLP3 inflammasome in particular, play a critical role in follicle loss during the normal reproductive ageing and raise the possibility that ovarian ageing could be delayed by suppressing inflammatory processes in the ovary.