Assuming that co-expression and co-storage of FVIII and VWF does occur in vivo, our data provide a molecular explanation for the fact that hemophilia A patients suffering from impaired complex assembly of FVIII and VWF in the circulation can be effectively treated with DDAVP. In particular, hemophilia A patients carrying a Tyr1680Phe, Ser2119Tyr, Arg2150His replacement or deletion of Ala2201, respond to DDAVP treatment by a concomitant increase of FVIII and VWF. In previous studies FVIII has been expressed in VWF-containing a-granules in mice. In this model, the benefit of FVIII Nutlin-3 release concomitant with platelet activation was convincingly demonstrated. Recently, targeting of FVIII to WPBs has been shown to restore hemostasis in a mouse model of hemophilia A. This finding further emphasizes the hemostatic potential of DDAVP-induced FVIII release from WPBs. Spermatogenesis is the process where male diploid spermatogonia develop into mature, haploid spermatozoa capable of fertilizing an oocyte. In all animals, this process involves a series of tightly regulated stages that include mitotic proliferation, meiotic division, and extensive cellular remodeling. The first step in spermatogenesis is the division of a self-renewing germline stem cell to produce a spermatogonial cell. This cell subsequently undergoes a series of mitotic divisions to produce spermatocytes that enter meiosis. Following meiosis the haploid spermatocytes undergo a series of morphological changes producing mature spermatozoa. Spermatogenesis has been extensively studied in Drosophila and mutations that affect each of the major steps in spermatogenesis have been described. Germline stem cells located at the apical tip of the testes divide asymmetrically to produce a new germline stem cell and a founder gonialblast. The gonialblast, enclosed in a two-cell syncytium cyst, undergoes four mitotic divisions to produce 16 primary spermatocytes that remain interconnected through cytoplasmic bridges as a result of incomplete cytokinesis. The 16 primary spermatocytes undergo two meiotic divisions to give rise to 64 spermatids that elongate and separate into individualized spermatozoa through a poorly understood process called individualization. During individualization protamines are incorporated into the chromatin resulting in nuclear condensation. Additionally, in a process called individualization, the membrane of the syncytium is remodeled to enclose each sperm. RNA interference has been implicated in normal male fertility. Failure to silence non-coding RNAs through PIWI causes a loss of germ line stem cells,. Similarly, mutations in the Argonaute family members aubergine and spindle-E de-repress Stellate which results in intracellular crystals in male germ cells causing sterility. Stellate silencing also requires Loquacious, a dsRNA binding protein that associates with Dicer-1 to process premiRNAs. Ago-3, an Argonaute protein enriched in the germline, has been implicated in both germline stem cell maintenance and Stellate silencing. Thus, several doublestranded binding proteins are required for normal male fertility.