Immunological aspects of ovarian function: role of the cytokines.

Interaction between the immune system and reproduction is multiple. Either directly or indirectly through their products, immune cells are associated with the regulation of every level of the hypothalamus-pituitary-ovarian axis. Immune cells are present in the ovaries and their numbers increase during the cycle. During the follicular development cytokines assist granulosa cell growth while inhibiting their differentiation. During the LH peak, an influx of immune cells occurs and several cytokines are released. The rupture of the follicle is considered as an inflammatory reaction. IL-1, TNF-alpha are the main cytokines involved in this process. During the luteal phase, the installation of the corpus luteum needs the setting up of neovascularization. Cytokines are probable candidates for this function, but they also promote cellular differentiation resulting in steroid synthesis. In the absence of pregnancy T lymphocytes and eosinophils are involved in corpus luteum regression. Their products are directly cytotoxic for the luteal cells. They attract macrophages which are locally activated to phagocytose the damaged luteal cells. They can induce apoptosis of endothelial and luteal cells through gene expression. Cytokines are members of a larger regulatory network residing in the ovary and involving hormones and growth factors. The various stages of ovarian cycle will be shown from an immunological point of view. Understanding the role of the cytokines should enable us to go beyond a purely descriptive stage, and allow us to envisage new ovulation induction therapy and treatment in certain cases of premature menopause.