COMMENTARY Site of the mammalian sperm physiological acrosome reaction J. M. Bedford1 Cornell Institute for Reproductive Medicine, Weill Medical College of Cornell University, New York, NY 10021 n mammals and the many other ani- oophorus, a multilayered mass of cells often spermatozoa. To reiterate, it shows that mals in which fertilization involves embedded in a hyaluronic acid-rich matrix. these spermatozoa frequently undergo the I the establishment of a penetration In early studies in the guinea pig and sev- AR within the cumulus before reaching the path through the egg coat, at the apex eral rodents, Austin and Bishop (2) re- zona pellucida and, using a fluorescent tail of the sperm head lies the acrosome— ported spermatozoa undergoing the AR tag, it also shows the key fact that such a membrane-limited organelle that houses within the cumulus and, mistakenly, they spermatozoa can then go on to fertilize. a complex of enzymes. For fertilization to then suggested that the reaction was a The observation that mouse spermato- occur, spermatozoa must first undergo the morphological manifestation of sperm ca- zoa with reacted acrosomes can then go acrosome reaction (AR), which involves pacitation—a sperm membrane-related on to adhere to and penetrate the zona point fusions between the outer acrosomal change undergone in the female tract, pe- pellucida has important implications for and overlying cell membrane. This reaction culiar to therian mammals, that finally efforts to characterize the sperm head releases the acrosome’s soluble lysins, confers on spermatozoa the ability to fer- surface component(s) involved in sperm/ which facilitate the creation of a path in tilize. Later, as seen in the electron micro- egg binding at fertilization. However, in the egg coat during penetration (although scope, rabbit spermatozoa at the fringe of considering other implications of this a variety of evidence now calls into ques- the cumulus oophorus generally had intact work, it needs to be shown eventually tion whether egg-coat lysis is the mecha- acrosomes, whereas most caught within that its findings represent the situation nism used by eutherian mammals). In during fertilization in vivo. Moreover, de- PNAS, using in vitro fertilization, Jin et al. spite the disappearance of the fluorescent (1) report their tracking of the site and Some spermatozoa acrosomal tag within the cumulus, it is timing of the AR in spermatozoa from presumed that the reacted acrosomal transgenic mice whose acrosome and reacting within the carapace is retained until and while the sperm tail midpiece were tagged with dif- sperm head binds to the zona surface. Al- ferent fluorescent markers. This approach, cumulus were then able though this has not been stressed in the which used video imaging, allowed them to to go on to fertilize literature, a broad cross-species survey of record that, compared with sperm on a na- the AR suggests that the reacted acrosome ked zona surface, the AR was generally the egg. in eutherian mammals has an unusual initiated more readily in the interstices of the stability and therefore, lifespan, possibly cell mass of the cumulus oophorus that sur- brought by an insoluble acrosomal matrix rounds the newly ovulated mouse egg. the cumulus had undergone some phase of component. This stability seems to be an Moreover, not only did the AR generally the AR by that time, as had most sperma- adaptation that then allows it to persist occur to a greater degree and often more tozoa bound to the zona pellucida (3). and tether the sperm head until penetra- rapidly in sperm penetrating the cumulus Subsequently, similar observations of the tion of the relatively formidable, dense than on a naked zona surface, but this was AR within the cumulus were made for zona matrix begins. also true for sperm interacting with naked spermatozoa of the Syrian (4, 5) and Chi- fi eggs in the presence of cumulus-invested nese hamster (6) and even man (7). Not Signi cance of the Cumulus Oophorus? oocytes. Most important, Jin et al. (1) es- long before that, however, inroads into the Finally, the paper of Jin et al. (1) serves to tablish by retroactive examination of re- problem of defining fertilization in molec- focus two further issues. Although the corded images that some spermatozoa ular terms had begun with the important identity of the AR induction agent in the reacting within the cumulus were then able finding that the (mouse) zona pellucida mouse cumulus oophorus is not known, to go on to fertilize the egg. Given that the comprises three glycoproteins—ZP1, ZP2, as a last point these authors note that in ARhasbeenexaminedindifferentways and ZP3 (8). Because cumulus-free eggs of several mammals, including man, pro- over the years and in a variety of mammals, most mammals can be fertilized in vivo or gesterone, which cumulus cells may pro- including man, why then is this current in vitro, the equally exciting observation duce, can induce the AR in capacitated study so important in the context of present a few years later that the mouse AR can be spermatozoa (13). This brings an impor- efforts to understand the mechanisms of induced by ZP3 (9) led to the view that the tant question as to whether the stimulus fertilization in eutherian mammals? zona pellucida induces the AR. Although for the AR in the cumulus oophorus seeming to discount previous observations and that on the zona surface, and the Initiation of the AR of the AR within the cumulus in other molecular steps involved, are the same or It has long been clear for the non- species and although, with occasional ex- very different. Second, the study serves to mammalian models of fertilization in which ceptions (10), most mouse studies were highlight a broader question as to the spermatozoa must create a penetration performed using cumulus-free eggs, this adaptive significance of the cumulus oo- path that, according to species, the AR is view of the zona pellucida as the physio- phorus, which appears to be unique to induced by the egg coat or often, by jelly logical inducer of the mammalian AR has eutherian mammals, the follicular cells that surrounds that coat. In eutherian mam- been a focus of other reports (11, 12), and mals, however, establishing the site where is now widespread. Thus, the observations the AR begins is made difficult by the fact of Jin et al. (1) represent a return to bi- Author contributions: J.M.B. wrote the paper. that the egg coat—the zona pellucida—is ological reality in this regard. The particu- The author declares no conflict of interest. surrounded for a species-variable number lar merit of their study lies not only in the See companion article on page 4892. of hours after ovulation by the cumulus observation of events in living mouse 1E-mail: [email protected]. www.pnas.org/cgi/doi/10.1073/pnas.1102296108 PNAS | March 22, 2011 | vol. 108 | no. 12 | 4703–4704 Downloaded by guest on September 24, 2021 being shed before ovulation even in zoa reach the zona pellucida, and in one compact and have little matrix in some marsupial mammals that have compara- case, the reacted spermatozoa penetrate species, but a hyaluronic acid-rich matrix bly small eggs. In fact, there is no single or and kill a line of cumulus cells in reaching expands the ovulated cumulus oophorus simple answer, because the cumulus oo- the zona surface (15). Because shrews are significantly where the eggs are fertilized phorus displays a variety of radiations in oftenconsideredtobeakintotheeu- in a spacious tubal ampulla, which is regard to its post-ovulatory life, its form, therian progenitors, this essential role of very common in eutherian mammals. Seen and its function. For instance, in two the cumulus in fertilization may represent in a range of species from ungulates and very different species of shrew, the dense the evolutionary situation, and based on primates to rodents and rabbits, this cumulus is stabilized by gap junctions and sperm head anatomy may apply at least expanded state of the cumulus may act has no intercellular matrix, but does have to other insectivores. However, although to provide a larger egg-associated target for an essential role in fertilization as the fertilization can occur in the absence of and sequester the very few spermatozoa inducer of the AR, which the zona pel- a cumulus in most mammals studied, its present in a voluminous ampulla (16), and lucida seems unable to stimulate (14). form and the postovulatory life can vary consistent with the present study, it may The acrosome is shed before spermato- widely. The cumulus oophorus may be foster early fertilization of the eggs (17). 1. Jin M, et al. (2011) Most fertilizing mouse spermatozoa 7. Chen C, Sathananthan AH (1986) Early penetration of 12. Florman HM, Jungnickel MK, Sutton KA (2008) Regu- begin their acrosome reaction before contact with the human sperm through the vestments of human eggs in lating the acrosome reaction. Int J Dev Biol 52:503– zona pellucida during in vitro fertilization. Proc Natl vitro. Arch Androl 16:183–197. 510. Acad Sci USA 108:4892–4896. 8. Bleil JD, Wassarman PM (1980) Structure and function 13. Melendrez CS, Meizel S, Berger T (1994) Comparison of fi 2. Austin CR, Bishop MWH (1958) Role of the rodent ac- of the zona pellucida: Identi cation and characteriza- the ability of progesterone and heat solubilized por- ’ rosome and perforatorium in fertilization. Proc R Soc tion of the proteins of the mouse oocyte s zona pellu- cine zona pellucida to initiate the porcine sperm acro- cida. Dev Biol 76:185–202. some reaction in vitro. Mol Reprod Dev 39:433–438.