Ovary in female aging

OvaryFemale reproductive senescence begins before birth and continues throughout a lifetime, culminating with menopause, the state of depletion of ovarian follicles. The female reproductive axis is unique in that it reaches a senescent state when other organs in the body are generally healthy. On average, women reach menopause at 50 years of age whereas their life expectancy is over 80 years. Hence, the majority of women will spend, or are spending, more than one-third of their life in a post-menopausal state. Epidemiological studies show that a late onset of menopause confers longevity and decelerates the appearance of much age-related morbidity, suggesting that delaying the onset of menopause will improve the health of aging women and therefore their quality of life. In this study, using animal models, we aim to develop an experimental procedure that will be conceptually applicable for delaying the natural onset of menopause in women. Once developed and successfully executed, this novel procedure may delay the onset of menopause by multiple years so that women may not experience menopause until they reach the age of 55, 60 or greater. Our project is based on the idea that by preserving ovarian tissues (cortices where most primordial follicles reside) at a young age when follicles are densely populated and then grafting this tissue back to her own ovary at an old age when follicles are sparsely populated, we will be able to increase the recipient’s follicle pool size. The increased follicular pool may therefore extend the functional life span of the ovary, resulting in a delay of menopausal onset. In this project, we aim to simulate human ovarian tissue grafting using well-established mouse menopausal models: naturally aging mice and 4-vinylcyclohexene diepoxide (VCD) injected mice. Briefly, young ovarian cortices will be transplanted to an older ovary, and we will determine whether the transplantation delays the onset of menopause of the recipient. Specifically, we will determine the effect of transplanting post-pubertal ovarian tissues to pre-, peri- and post-menopausal animals, and measure the on the onset of menopause. Our laboratory has successfully established an ovarian tissue transplantation protocol using the C57BL/6 strain of mice. Some studies in rodent models, however, have shown that the hypothalamus of a middle-aged female (when the ovary is functional) is less sensitive to preovulatory estradiol positive feedback stimulation, resulting in a reduction in the number of activated GnRH neurons and a delayed or attenuated secretion of LH from the pituitary. These observations may indicate that hypothalamic senescence may precede ovarian aging with the possibility that ovarian cortices may go through accelerated aging if transplanted to an older recipient. However, other studies suggest that ovarian aging itself is the predominant factor for the aging of reproductive axis and therefore the onset of menopause. In this study, we will use our ovary transplantation procedure to resolve these conflicting reports by measuring the aging rate of ovarian cortices when transplanted to different age groups of mice and the aging rate of the hypothalamus when varying age groups of mice receive ovarian cortices from different age groups of mice. Show is a microscopic image taken from an ovary that received an ovarian tissue graft that was taken from a green fluorescent mouse.