Fertilization in Mammals

SUMMARY The mammalian egg is made up of the protoplasmic vitellus, which consists of cytoplasm, nucleus and yolk material, surrounded successively by a thin plasma membrane, a fluid‐filled perivitelline space, and the zona pellucida which is mucoprotein in nature. About the whole there exists the cumulus oophorus consisting of cells embedded in a hyaluronic‐acid matrix. The spermatozoon is composed of a head, bearing a cap or acrosome, and a tail. The latter is subdivided into the neck, the mid‐piece with its mitochondria and possibly Golgi material, the main‐piece, and the end‐piece. The evidence indicates that, within the female tract, both eggs and spermatozoa subsist as aerobic organisms. Presumably, too, fertilization in mammals is adapted to an aerobic environment. The acrosome is known to contain polysaccharide and probably carries the enzymes and other agents that are responsible for penetration of the cumulus, for attachment to and penetration of the zona, and for eliciting a specific response from the vitellus upon contact with its surface. This response is complex and finds rapid expression in the zona reaction and the vitelline block to polyspermy, both of which tend to exclude extra spermatozoa from the egg, and slower expression in the absorption of the spermatozoon into the vitellus, and in the activation of the egg. Activation is associated with resumption of the second meiosis, which completes the process of maturation, with extrusion of the second polar body, and with contraction of the vitellus. Shortly after entry into the vitellus, the nuclear part of the spermatozoon head undergoes transformation into a male pronucleus which becomes recognizable concurrently with the genesis of the female pronucleus from the egg chromosomes. The pronuclei develop at equivalent rates, though in some species the male pronucleus maintains a much larger volume than the female. Development of the pronuclei is competitive and at the expense of limited cytoplasmic stores of formative material, which largely determine the ultimate size of the pronuclei. There is evidence that throughout the whole of fertilization the changes undergone by the male and female elements are normally closely correlated and interdependent. The nucleoli are composed chiefly of basic proteins with some phospholipids and acid phosphatases, and may be involved in the synthesis of nucleoplasmic substances which eventually pass into the cytoplasm. The functions of pronuclei may include production of gene‐modified templates or plasmagenes of significance for future embryonic growth, and the synthesis of extra desoxyribonucleic acid preparatory to cleavage of the egg. Both growth and function of pronuclei are probably dependent upon the enzymic activity of cytoplasmic mitochondria. As a general rule the spermatozoon tail enters the vitellus; it contributes mitochondria and possibly Golgi material to the embryo. Failure of entry of the tail, however, need not prejudice normal development. Eggs remain capable of normal fertilization and development for less than 24 hr. in most mammals. Early evidence of deterioration or ageing appears soon after ovulation, and is shown by reduction in the rate of the zona reaction and particularly of the block to polyspermy. Experimental manipulation of eggs accelerates ageing; elevated temperatures are particularly detrimental to the mechanisms normally excluding extra spermatozoa. Polyspermy occurs spontaneously with a frequency of 1 or 2%. The extra male pronuclei, at least in the rat, participate in syngamy and so give rise to a triploid embryo which is most unlikely to survive to birth. Gynogenetic, androgenetic or parthenogenetic development has very rarely been seen under normal circumstances in most species, but the incidence of early parthenogenesis may be greatly increased by experimental procedures. The resulting embryos are probably non‐viable. Both spermatozoa and eggs may be manipulated and stored in vitro without loss of the capacity to take part in normal fertilization in vivo ; spermatozoa especially are resistant to environmental change. It is possible, but as yet by no means certain, that spermatozoon entry followed by fertilization in vitro has been observed. The phenomena of fertilization involve the entire egg and show many variations that are attributable not only to environmental differences but also to species and even strain differences.