Pöllänen P, Cooper T G, Kokk K, Saari T, Setchell B P
Department of Anatomy, University of Turku, Finland.
J Reprod Immunol. 1997 Feb;32(3):221-40. doi: 10.1016/s0165-0378(96)01003-0.
Development of contraceptive vaccines has recently raised much interest following the cloning of the sperm and oocyte components involved in the sperm-oocyte interaction. The main difficulty of immunocontraception in the male is the poor access of antibodies to the luminal compartment. As recent literature suggests that many substances are transported to the testis by receptor-mediated or fluid-phase transcytosis, the dependence of the transport of IgG on the Fc receptor was studied in the present investigation by comparing the penetration of whole IgG and the F(ab')2 fragment of IgG to the testis and epididymis. The maximum volume of distribution (Veq) for the F(ab')2 fragment was significantly higher than that for whole IgG in the testis of 30-60-day old rats, in the caput and cauda of 30- and 45-day old rats and the corpus of 45-day old rats. The speeds at which equilibrium between tissue extracellular fluid and serum was reached (K) for the F(ab')2 fragment and whole IgG were significantly different in the testicular capsule of the 60-day old, in the caput and corpus of the 45- and 60-day old and in the cauda of the 45-day old rats. The microvascular permeabilities (PE) to the F(ab')2 fragment were more than 2-fold higher than those to whole IgG in the testis of the 20-, 45- and 60-day old, in the testicular capsule of the 20- and 45-day old, in the caput of 20-, 30- and 60-day old and in the corpus of 20-day old rats. The PE to whole IgG was more than 2-fold higher than that to the F(ab')2 fragment in the cauda of the 45-day-old rats. The PE to the F(ab')2 fragment increased steadily from 20 to 60 days of age in the testis and caput, but in the corpus there was a more abrupt increase between 30 and 45 days of age. In the cauda, PE remained in the same range of magnitude throughout pubertal development. These results suggest that the F(ab')2 fragment reaches the lumen of the reproductive tract more easily than whole IgG from 30 days of age onwards in the testis, whereas in the caput, corpus and cauda epididymidis the rate at which F(ab')2 fragment reaches the lumen increases only temporarily at the time of appearance of spermatozoa in the lumen. Transport of IgG to the male reproductive tract is thus unlikely to be mediated by Fc receptors.
随着参与精子 - 卵母细胞相互作用的精子和卵母细胞成分的克隆,避孕疫苗的研发最近引起了广泛关注。男性免疫避孕的主要困难在于抗体难以进入管腔部分。由于最近的文献表明许多物质通过受体介导或液相转胞吞作用转运至睾丸,本研究通过比较完整IgG及其F(ab')2片段进入睾丸和附睾的情况,研究了IgG转运对Fc受体的依赖性。在30 - 60日龄大鼠的睾丸、30日龄和45日龄大鼠附睾头和尾以及45日龄大鼠附睾体中,F(ab')2片段的最大分布容积(Veq)显著高于完整IgG。在60日龄大鼠的睾丸被膜、45日龄和60日龄大鼠的附睾头和体以及45日龄大鼠的附睾尾中,F(ab')2片段和完整IgG达到组织细胞外液与血清平衡的速度(K)显著不同。在20日龄、45日龄和60日龄大鼠的睾丸、20日龄和45日龄大鼠的睾丸被膜、20日龄、30日龄和60日龄大鼠的附睾头以及20日龄大鼠的附睾体中,F(ab')2片段的微血管通透性(PE)比完整IgG高2倍以上。在45日龄大鼠的附睾尾中,完整IgG的PE比F(ab')2片段高2倍以上。在睾丸和附睾头中,F(ab')2片段的PE从20日龄到60日龄稳步增加,但在附睾体中,在30日龄到45日龄之间有更突然的增加。在附睾尾中,整个青春期发育过程中PE保持在相同的数量级范围内。这些结果表明,从30日龄起,在睾丸中F(ab')2片段比完整IgG更容易到达生殖道管腔,而在附睾头、体和尾中,F(ab')2片段到达管腔的速率仅在管腔中出现精子时暂时增加。因此,IgG向雄性生殖道的转运不太可能由Fc受体介导。