Normal spermatogenesis and fertility in germ cell-specific genomic androgen receptor knockout mice

Abstract

Objective: The purpose of the present study is to generate the seprmatocyte specific androgen receptor knock out (ARKO) mice using cre-lox strategy and to study its influence on spermatogenesis. Design: A tissue-specific knock-out animal model. Materials and Methods: Previous, we have generated a strain of mice carrying a fragment of lox sequence within the androgen receptor genome (flox-AR). In the present study, we mated the flox-AR mice with a mice carrying cre recombinase driven by spermatocyte specific promoter synaptonemal complex protein 1 (Sycp1-Cre mice). Since Sycp1 is only expressed at the leptotene-zygotene stage of spermatocyte, the generated Sycp1-ARKO male mice lost androgen receptor at the process of spermatogenesis after leptotene-zygotene stage. We compared the wild type (wt) and the Sycp1-ARKO mice on the fertility, AR expression, sperm count and histology of seminiferous tubules to determine how the spermatogenensis was influenced. The efficiency of the knock-out is confirmed by checking the genotypes of female offspring from the Sycp1-ARKO fathers and the wt C57BL/6J mothers. Results: Histology analyses indicate that each stage of spermatogenesis is normal and the expression of AR in Sertoli, Leydig, and peritubular cells is unaffected in Sycp1-ARKO mice. Sperm count and motility in epididymis from Sycp1-ARKO are similar to that of the wt siblings. The overall knock-out efficiency is 78%. However, 3 of 4 Sycp1-ARKO mice show 100% efficiency. Conclusion: The results suggest that the expression of androgen receptor in the male germ cells beyond the spermatocyte stage is redundant for the sperm maturation.