BIOLOGY OF SPERMATOZOA 



745 



wall at the attachment site of the sper- 

 matophore and then passing into vascular 

 channels through which they actively mi- 

 grate to the ovary where sperm penetration 

 and fertilization occur. 



VI. Immunologic Problems Associated 

 with Spermatozoa 



A. ANTIGENICITY OF SPERM 



The antigenic properties of spermatozoa 

 have been recognized since the turn of the 

 century through the pioneer studies of 

 Landsteiner (1899), Metchnikoff (1899), 

 and Metalnikoff (1900), who, almost simul- 

 taneously, discovered that guinea pigs pro- 

 duce antibodies against heterologous and 

 homologous sperm. Landsteiner's work is 

 of classic interest not only because it was 

 barely the first, but also because he used 

 an in vivo method to demonstrate an im- 

 mune response against sperm. Bull sperma- 

 tozoa, he found, remain active when in- 

 jected into the peritoneal cavity of normal 

 guinea pigs, whereas if the pigs have been 

 l^reviously injected parenterally with bull 

 sperm, the peritoneally administered sperm 

 rapidly become immotile. These early dis- 

 coveries were to be followed by a great 

 wave of interest in sperm antigens, generally 

 assayed by in vitro methods, and attempts 

 to induce sterility in female animals by in- 

 jection of suspensions of spermatozoa or 

 testicular homogenate. After a lull in ac- 

 tivity, interest was rekindled by the de- 

 velopment of new immunologic procedures 

 and concepts, and the awareness of the im- 

 l^lication of immune processes to problems 

 of fertility and fertility control (Katsh, 

 1959a; Tyler and Bishop, 1961). 



Specific antigens have been demonstrated 

 in, or on, spermatozoa of many mammals, 

 including the rabbit, rat, mouse, guinea pig, 

 dog, ram, bull, and man. The methods used 

 for their determination have generally in- 

 volved the classical serologic procedures — 

 agglutination, immobilization, precipitin, 

 and complement fixation — and the more 

 recently introduced Oudin and Ouchterlony 

 agar gel-diffusion techniques. The results, in 

 general, indicate a relatively high degree 

 of species-specificity, but some cross-re- 

 activity does occur (Mudd and Mudd, 1929; 



Henle, 1938; Smith, 1949a). Tissue-spec- 

 ificity is also incomplete. The AB-blood 

 group antigens, for example, as pointed out 

 previously, are present in human sperm 

 (Landsteiner and Levine, 1926; Gullbring, 

 1957), and a comparable similarity of 

 sperm-erythrocyte agglutinins has been 

 claimed in cattle (Docton, Ferguson, Lazear 

 and Ely, 1952). Common antigenicity be- 

 tween brain and testicular tissue has been 

 demonstrated (Lewis, 1934; Freund, Lipton 

 and Thompson, 1953; Katsh and Bishop, 

 1958) and may relate to the mature germ 

 cells themselves. 



As routinely determined by means of ag- 

 glutination or immobilization of fresh sperm 

 in the presence of antisperm serum, the 

 antigenicity of the gametes is customarily 

 attributed to surface moieties and exposed 

 reactive groups. Smith (1949b), however, 

 called attention to the reactivity of the 

 more deeply situated antigenic substances 

 in her study of heterologous reactions among 

 rodent sperm. In part, of course, the mask- 

 ing and unmasking of combining groups are 

 a function of the technical procedures to 

 which the cells are exposed and arc features 

 wliich have to be circumvented or recog- 

 nized in investigations of this kind. The 

 surface properties of, and "leakage" from, 

 spermatozoa are known to change with 

 storage, dilution, washing, and centrifuga- 

 tion, which, when severe enough (Mann, 

 1954), can be expected to alter the apparent 

 natural antigenicity of the cells (Smith, 

 1949b; cf. Pernot, 1956). 



The number of antigenic sul)stancL's on 

 the sperm surface is a moot ])oint and may 

 prove merely a matter of definition, if not 

 of semantics, depending on the techniques 

 involved (see Table 3 in Tyler and Bishop, 

 1961). Henle, Henle and Chambers (1938) 

 localized three distinct antigens in bull 

 sperm by preparing, in rabbits, agglu- 

 tinating and complement-fixing antibodies 

 against the head and tail fractions. One 

 antigen was found to be head-specific, an- 

 other tail-specific, and the third common to 

 both head and tail of the intact sperm. On 

 the other hand, when the agar-diffusion 

 method was applied to the study of sperm 

 antigenicity, many reactive substances ap- 

 peared which seemed to be surface antigens. 



