There are many signalling pathways, transcription factors and proteins that have been linked to CAVD, such as osteoblastic differentiation and skeletal morphogenesis regulating TF Runt-Related Transcription Factor 2 (RUNX2), bone morphogenic protein 2 (BMP2), several matrix metalloproteinases and interleukins, Tumour Necrosis Factor-Alpha (TNFα); however, the exact factors driving the CAVD progression are not known [57]. Here, TNF is linked to congenital bilateral aplasia of vas deferens from CFTR mutation.