Cellular and molecular aspects of ovarian follicle ageing

Abstract

It is well established that age-related decline of the biological capacity of a woman to reproduce is primarily related to the poor developmental potential of her gametes. This renders female ageing the most significant determinant of success in IVF. Starting with a reference picture of the main molecular and cellular failures of aged oocytes, granulosa cells and follicular microenvironment, this review focuses on age-related biochemical mechanisms underlying these changes. According to the most relevant concept of ageing, age-associated malfuction results from physiological accumulation of irreparable damage to biomolecules as an unavoidable side effect of normal metabolism. More than a decade after the free radical theory of ovarian ageing, biological and clinical research supporting the involvement of oxidative injuries in follicle ageing is discussed. Looking for the aetiology of oxidative stress, we consider the effect of ageing on ovarian and follicular vascularization. Then, we propose a potential role of advanced glycation end-products known to be involved in the physiological ageing of most tissues and organs. We conclude that future investigation of age-related molecular damage in the different ovarian components will be imperative in order to evaluate the possibility to save or rescue the developmental potential of aged oocytes.

Protein modification as oxidative stress marker in follicular fluid from women with polycystic ovary syndrome: the effect of inositol and metformin

“…Thiols, in fact, have the characteristic to be oxidized in an almost irreversible manner and this identifies them as key components in the mechanism involved in redox balance. In humans, research on ROS and oxidative stress is hampered by methodological difficulties in assessing the levels of markers of oxidative stress in biological samples [29,30]. In particular, the direct evaluation of the level of oxidative stress in cell-free biological fluids is very difficult since they lack ROS producing cells.…”

Age-related Accumulation of Non-heme Ferric and Ferrous Iron in Mouse Ovarian Stroma Visualized by Sensitive Non-heme Iron Histochemistry

“…The accumulation of damage exerted by increased levels of ROS is believed to be involved in ovarian aging (Tarin 1995(Tarin , 1996. Furthermore, it has been proposed that ROS play a role in the decline of ovarian function due to the aging of oocytes or reduced ability of granulosa cells (Agarwal et al 2005;Yin and Chen 2005;Tatone et al 2008). Although the mechanisms of ovarian functional decline due to ROS have been suggested by a decrease in enzymatic or nonenzymatic antioxidant defense, the details of the mechanisms are unclear (Tatone et al 2008).…”

Homeobox A7 increases cell proliferation by up-regulation of epidermal growth factor receptor expression in human granulosa cells

“…Granulosa cells surround the developing oocyte, providing a critical microenvironment for follicular growth. Multiple granulosa cell dysfunctions lead to disordered ovulatory and ovarian function [1]. Moreover, granulosa cell tumors (GCTs) are serious ovarian neoplasms that can occur in women of all ages [2].…”