Phosphodiesterases and regulation of female reproductive function

The function of the mammalian follicle is regulated by circulating gonadotropins and a myriad of local paracrine regulations functioning within the ovary. Cyclic nucleotide signaling plays an essential role in mediating both these endocrine and paracrine regulations. Given their role in controlling cyclic nucleotide levels, cyclic nucleotide phosphodiesterases (PDEs) are critical for ovarian function. PDEs modulate gonadotropin responses in the somatic compartment of the ovarian follicle. Specific PDEs are also essential for the oocyte entry and exit from the meiotic cell cycle. This review summarizes the function and regulation of PDEs in the somatic compartment and in the oocyte, and highlights the potential of PDEs as targets to improve assisted reproduction, as well as for fertility control.

► PDEs are differentially expressed in the somatic and germ cell compartments of the follicle.
► PDE4s are regulated by gonadotropins.
► PDE4 inhibitors enhance the sensitivity of granulosa cells to gonadotropins.
► PDE3A is critical for oocyte maturation.