Does the Akt pathway play a role in follicle activation after grafting of human ovarian tissue?

Abstract

The aim was to elucidate the delay in and mechanisms of follicle activation after ovarian tissue transplantation, with particular emphasis on the role of the Akt signalling pathway. Ovarian tissue was collected from six patients and divided into four fragments in each case: one for control purposes and three for grafting to immunodeficient mice for 3, 7 and 21 days. Follicle density, classification, growth and atresia, and the Akt pathway were analysed. A significant decrease in primordial follicles and significant increase in growing follicles were detected 3 days after transplantation (both P=0.01). More than 50% of follicles were atretic after 3 days, and a further 50% after 7 days of grafting. Akt phosphorylation was significantly elevated in primordial follicles after 3 days of grafting (P=0.048). This study confirms that primordial follicle activation is an early event after transplantation, and significant follicle death also contributes to the burnout effect, eventually resulting in early depletion of the ovarian reserve. Increased Akt phosphorylation on day 3 post-grafting suggests it plays a role in follicle activation and subsequent burnout.