Studies on Sertoli cells and germ cells, as well as testes from CFTR knockout mice or a cryptorchidism model, indicate the involvement of CFTR in spermatogenesis through the HCO(3)(−)/sAC/cAMP/CREB(CREM) pathway and the NF-kappaB/COX-2/PGE(2) pathway.34 Studies on male infertility have mostly focused on studying the effect of the allele and genotype frequencies on polymorphisms of key genes that were identified to play a major role in various disease conditions associated with male infertility, such as azoospermia or severe oligozoospermia. This evidence concerns the gene CREM and Azoospermia.