Human Reproduction Update Advance Access published online on January 31, 2008
Human Reproduction Update, doi:10.1093/humupd/dmm048
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Cellular and molecular aspects of ovarian follicle ageing
1 Department of Biomedical Sciences and Technologies, University of L’Aquila, L’Aquila, Via Vetoio 67100, Italy 2 Department of Basic and Applied Biology, University of L’Aquila, L’Aquila, Italy 3 Department of Reproductive Medicine and Child Development, Division of Obstetrics and Gynecology, University of Pisa, Pisa, Italy 4 Department of Obstetrics, Gynecology and Perinatology, S. Andrea Hospital, La Sapienza University, Rome, Italy 5 Department of Experimental Medicine, University of L’Aquila, L’Aquila, Italy 6 Department of Surgery, Section of Biology, University of Siena, Policlinico Le Scotte, Siena, Italy 7 Department of Evolutionary Biology, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy
To whom correspondence should be addressed at: 8 Correspondence address. Tel: +39-0862-433441; Fax: +39-0862-433433; E-mail: ctatone{at}univaq.it
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.
Key words: antioxidants / female infertility / follicle development / ovarian function / oxidative stress
Received on August 31, 2007; revised November 12, 2007; accepted on December 9, 2007