P-605 Hypoxia leads to diminished ovarian reserve in an age dependent manner

Abstract Study question To determine whether hypoxic ovarian damage is due to increased growth and follicles “burnout” or apoptosis, this age dependent. Summary answer Direct tissue hypoxia causes activation recruitment of dormant without apoptotic changes. This effect dependent, more pronounced in adult- versus newborn ovaries. What known already In a previous study we have shown that perinatal premature initiation leading diminished reserve. Other reports also linked intrauterine deprivation conditions, delivery small for gestational newborns with reserve follicular exhaustion. Nevertheless, an indirect mechanism influencing follicle under such as the release stress related hormones cannot be ruled out. design, size, duration Animal studies were carried out using adult 6-week-old (n = 8) one-day-old 20) ICR (CD-1) female mice. Throughout study, animals housed alternating 12-h light/dark cycle access food water ad libitum, constant room humidity temperature. Animals sacrificed ovaries harvested immediately cultured Leibovitz media L-Glutamine 10% Fetal Bovine Serum. Participants/materials, setting, methods Ovarian from dams pups was 3 hours at 37oC (1% O2 99% N2) normoxia (21% 5% CO2). Afterwards embedded 4% formaldehyde further processing analyses. Sections stained H&E counts. For immunohistochemistry, sections Ki-67 (proliferation marker), anti-Caspase anti-FOXOp (apoptosis markers). Main results role chance Hypoxia led significant decrease percentage primordial total compared normoxia, both among (3.17±2.75% vs. 17.89±4.4%; p 0.004 40.59±14.88 81.92±31.56%, 0.001 respectively). accompanied by concomitant increases percentages growing (primary secondary) follicles. Strikingly, (6 fold 2 Ki67 staining indicated cell proliferation scores granulosa cells following . Both Caspase FoxoP did not detect any changes markers apoptosis either oocytes, cells, theca stromal when exposed normoxia. Limitations, reasons caution model performed mice generalization human physiology remains determined. Wider implications findings We hereby show direct apoptosis. dependent being Taken together it supports “burn out” potential induced loss Trial registration number IL-117-08-2017