Sperm acrosome antigen-1, a molecule crucially involved in the regulation of the acrosome reaction: further immunohistochemical characterization towards immunocontraceptive applicability

Introduction: Sperm acrosome antigen-l (SAA-l) is a molecule of 220 kD located on the acrosome of sperm from the human and other mammalian and lower species. SAA-l was initially characterized using first generation monoclonal antibody (mab) AG7. AG7 inhibits the human sperm acrosome reaction (AR) and attenuates progesterone-induced calcium influx. Furthermore, AG7 inhibits fertilization in the mouse in vitro and in vivo. The cross-reactivity of AG7 and second generation mabs to SAA-l was examined in the human. Materials and Methods: AG7 and second generation mabs were tested for their effect on the progesterone-induced human sperm AR, and subsequently utilized for a broad immunohistochemical screening of tissue specificity. Electron microscopy (EM) was performed on selected tissues to determine the subcellular localization of SAA-l. Results: All second generation mabs against SAA-l inhibited the progesterone-induced AR at various degrees. Although AG7 showed only weak cross-reactivity to a few secretory and neuroendocrine tissues (pancreas, parotid, follicular epithelium, adrenal marrow, neurons and peripheral nerves), some of the second generation mabs displayed strong cross-reactivity to a larger panel of secretory tissues, additionally including endometrium, breast, stomach, sublingual gland, and tracheal and epididymal epithelium. Using EM, SAA-l was localized to the cell-membrane in neurons of the human brain as well as in testicular sperm, whereas in pancreas, specific staining was observed on the endoplasmic reticulum. Conclusion: Although SAA-I has a proven role in fertilization, its applicability in immunocontraception may be limited by the apparent cross-reactivity of mabs to SAA-l with secretory and neuro-endocrine tissues. Further biochemical characterization may allow to define peptide epitopes with exclusive sperm specificity.