Physiopathologie de l'insuffisance ovarienne prématurée : faits et perspectives.

Abstract

L' insuffisance ovarienne prematuree est une maladie frequente dont la prevalence est estimee a 2 % de la population feminine. Elle se traduit cliniquement par une amenorrhee primaire ou secondaire survenant avant l' age de 40 ans avec des concentrations elevees de gonadotrophines et de faibles concentrations d' oestradiol. Cette affection souleve deux problemes pour le clinicien: la carence hormonale chez ces patientes jeunes et la prise en charge de leur infertilite. Plusieurs etiologies ont ete identifiees: toxiques (chimiotherapie et/ou radiotherapie), dysimmunitaires et genetiques. La physiopathologie de cette affection demeure cependant mal connue. L' identification des genes impliques dans la croissance, la selection et l' atresie folliculaire, et la connaissance des mecanismes moleculaires conduisant a l' apoptose folliculaire devraient permettre de mieux elucider ce phenomene.

Premature ovarian failure (POF) is an heterogeneous syndrome. Women can present with primary amenorrhea or secondary amenorrhea occurring before the age of 40. Nearly 2% of the female population is affected by this disorder. Its pathophysiology still remains obscure. Different hypotheses can be proposed: a reduction in the number of primordial follicles, an accelerated or increased atresia, a defect in the genes involved in follicular recruitement and finally a blockade in follicular growth. Up to now, few causes have been identified: toxic, autoimmune and genetic. Chemotherapy and radiotherapy lead either to a reversible or to a permanent gonadal dysfunction, according to the type of drug, the doses and the patient's age at the time of treatment. Polyendocrinopathies and animal models seem to involve autoimmune disorders as a cause of premature ovarian failure. The mechanisms, through which mutations in the AIRE gene responsable for the APECED syndrome can leed to ovarian insufficiency, are still unknown. It is likely that studies on the function of the AIRE protein, a transcription factor, might improve our knowledge. Among genetic causes, X monosomy as in Turner syndrome or X deletions and translocations are known to be responsible for POF. The genes or the X chromosome involved in ovarian function are still unknown. Furthermore, autosomal abnormalities have been identified as mutations of LH and FSH genes, their receptor genes, chromosome 3q, Ataxia-telangiectasia genes, the AIRE gene. Meanwhile, the cause of POF remains idiopathic in most cases. In the future, a better knowledge of the cellular and biochemical components implied in folliculogenesis and apoptosis should elucidate the mechanisms of POF. [References: 51]