Meiotic arrest and germ cell apoptosis in androgen-binding protein transgenic mice

The fundamental role of androgen-binding protein (ABP) in spermatogenesis r emains obscure after nearly 25 yr since its first characterization. In the present investigation, we used a transgenic mouse model that overexpresses rat ABP to examine the potential involvement of this protein in the regulat ion of processes occurring during spermatogenesis. Specifically, homozygous or heterozygous transgenic mice were analyzed in terms of spermatogenic pr ogression, DNA fragmentation pattern, and germinal cell ploidy status. All animals homozygous for transgenic ABP exhibited an increased accumulati on of primary spermatocytes and cells at metaphase with abnormal morphology and localization within the seminiferous epithelium. Analysis of DNA fragm entation by in situ techniques and agarose gel electrophoresis provided evi dence for an increased occurrence of apoptosis in the transgenic animals, p rincipally involving pachytene spermatocytes and cells at metaphase. Flow c ytometric analysis of the DNA content of isolated germ cells revealed a red uction in the number of haploid cells, an increase in the number of tetrapl oid cells, and the appearance of a hypotetraploid cell population, consiste nt with degenerating primary spermatocytes. In mice heterozygous for the tr ansgene, the effects were less prominent, and the degree to which spermatog enesis was compromised correlated with the levels of ABP messenger RNA in i ndividual animals. The present results are interpreted to suggest that ABP can act as a modulator of spermatogenesis by regulating completion of the f irst meiotic division of primary spermatocytes.