Analysis of the testicular phenotype of the follicle-stimulating hormone beta-subunit knockout and the activin type II receptor knockout mice by stereological analysis

This study evaluated the role of FSH and activin A on testicular function u sing quantitative stereological analysis of testicular cell types in mice w ith targeted disruption of genes encoding the FSH beta -subunit and the act ivin type IIA receptor (ActRIIA). Using the optical dissector technique, th e numbers of Sertoli cells and germ cells per testis were determined. Testi s weights in homozygous males lacking the FSH beta gene or the ActRIIA gene were decreased approximately 60% compared with wild-type or respective het erozygotes. Sertoli cell numbers decreased in both homozygous mice by 30-39 %, and there was a comparable decline in germ cell numbers in both models. The degree of germ cell attrition increased in the later stages of spermato genesis from a 46% reduction of spermatogonia to a 60% decrease in round sp ermatids. As the FSH levels are decreased in both models, the cellular lesi on in both is most likely due to the FSH deficiency. Although the decrease in the Sertoli cell complement represents one cause of lower germ cell numb ers, the ability of Sertoli cells to nurture germ cells is compromised by t he lower FSH levels, as shown by a decrease in the round spermatid to Serto li cell ratios in both homozygous models. We conclude that the defects in F SH beta -subunit gene knockout and ActRIIA knockout mice are related to dim inished FSH action on both Sertoli cell proliferation and the capacity of S ertoli cells to nurture germ cells.