Useful Blog Posts
The process of fertilization takes place long after other steps in reproduction like spermatogenesis, sperm transport, and sperm swimming through the reproductive tract. Once the sperm have reached the egg, or oocyte, they begin the process of binding to the egg via the acrosome reaction.
The acrosome, a structure at the head of sperm, contains enzymes that are required to bind and break through the coating of the egg. The acrosome reaction begins as the sperm approaches the zona pellucida (ZP). The ZP is a mixture of sugars and proteins that surround the outer membrane of an egg. When the ZP binds sperm, enzymatic interactions provide almost a “lock and key” recognition that allows the process to continue.
The enzymes stored in the acrosome play a number of functions, all required to penetrate the egg. Additionally, ion channels are involved in a process called sperm hyperactivation, which is crucial to fertilization. The whipping of the tail of sperm provides a mechanical boost to the sperm, thus allowing further penetration.
Once the sperm has made it’s way past the ZP, the cortical reaction occurs, where new enzymes stored in granules are expelled. These enzymes harden the ZP, making it impermeable to other sperm.
At this point, the membranes of the sperm and egg are prepared to fuse. Once they do, their genetic material combines to make a mature ovum.
All of these processes are tightly regulated, complicated orchestrations with multiple failure points. Some of them have been identified as possible targets for male contraception. MCI is funding work investigating the TSSK and CRISP families of proteins, as well as the interaction between the sperm / egg recognition targets Juno and Izumo.
A drug that prevents fertilization has some exciting potential, as theoretically they could be used by both men and women, providing true non-hormonal equity to the contraceptive world. Additionally, it would have the benefit of a short onset time, and could be taken possibly a few hours before sexual intercourse.
Male Reproduction & Contraception
The science behind male reproduction can be challenging, yet it is critical to understand the biology in order to know how the male contraceptives of the future will function. In an effort to make this science more accessible, we have developed a series of primers about male reproduction and contraception:
Inoue, N; Satouh, Y; Ikawa, M; Okabe, M; Yanagimachi, R (2011). “Acrosome-reacted mouse spermatozoa recovered from the perivitelline space can fertilize other eggs”. Proceedings of the National Academy of Sciences. 108 (50): 20008–11.
Mou L, Xie N. Male infertility-related molecules involved in sperm-oocyte fusion. J Reprod Dev. 2016;63(1):1-7.
Ikawa M, Inoue N, Benham AM, Okabe M. Fertilization: a sperm’s journey to and interaction with the oocyte. The Journal of clinical investigation 2010; 120:984-994
Sosnik J, Miranda PV, Spiridonov NA, Yoon SY, Fissore RA, Johnson GR, Visconti PE. Tssk6 is required for Izumo relocalization and gamete fusion in the mouse. J Cell Sci 2009; 122: 2741–2749.
Da Ros VG, Maldera JA, Willis WD, Cohen DJ, Goulding EH, Gelman DM, Rubinstein M, Eddy EM, Cuasnicu PS. Impaired sperm fertilizing ability in mice lacking Cysteine-RIch Secretory Protein 1 (CRISP1). Dev Biol 2008; 320: 12–18.