COVER: From “Deficiency in the Omega-3 Fatty Acid Pathway Results in Failure of Acrosome Biogenesis in Mice” by Manuel Roqueta-Rivera, Timothy L. Abbott, Mayandi Sivaguru, Rex A. Hess, and Manabu T. Nakamura. Biol Reprod 2011; 85:721-732. Published online in BOR-Papers In Press June 8, 2011; DOI: 10.1095/biolreprod.110.089524. A 3D image of a cap-phase round spermatid from wild-type mouse testis taken by laser-scanning confocal microscopy. A localized accumulation of the acrosomal marker acrosin (red) has organized against the left of the nucleus (blue) at the acrosome, though some remains dispersed throughout the cytosol. An omega-3 fatty acid, docosahexaenoic acid (DHA) is enriched in testicular membrane phospholipids, but its function is poorly understood. The Fads2 gene encodes an enzyme required for the endogenous synthesis of DHA. Using Fads2-null mice (Fads2-/-), our preceding studies have shown that DHA deficiency causes an arrest of spermiogenesis and male infertility, both of which are reversed by dietary DHA. In this study, we investigated a cellular mechanism underlying the DHA essentiality in spermiogenesis. In the Fads2-/- spermatids, acrosin was scattered throughout the cytoplasm, indicating the release of proacrosomal vesicles that contain acrosin. However, in contrast to the localized accumulation seen in the wild-type spermatids, acrosin failed to accumulate in the acrosome of Fads2-/- spermatids, suggesting an essential role for DHA in proacrosomal vesicle fusion. Cover design and layout: Jane Tenenbaum, Tenenbaum Design, Cambridge, Massachusetts. Biology of Reproduction is printed with soy-based inks on acid-free paper by Allen Press, Inc., Lawrence, Kansas.