Expression of PP1γ1 and PP1γ2 in testicular germ cells and Sertoli cells, respectively, is required for normal spermatogenesis

Male mice lacking Ppp1cc gene, which encodes the protein phosphatase isoforms PP1γ1 and PP1γ2, are infertile due to impaired spermatogenesis. Mutant females are fertile and normal suggesting that PP1α, PP1β can substitute for the loss of PP1γ isoforms. Transgenic expression of PP1γ2, but not PP1γ1, in testis of Ppp1cc null mice, driven by the Pgk2 promoter, restored spermatogenesis. However transgenic mice were infertile since sperm were immotile with varying degrees of morphological defects. The aims of this study were to determine how the spatio‐temporal expression of PP1γ isoforms within testis is required for spermatogenesis. We used the endogenous promoter of Ppp1cc to drive expression of the PP1γ isoforms. In‐silico and experimental studies predicted that the promoter as a 2.6 kb fragment upstream of the transcription start site of Ppp1cc . Our results show that this genomic region is able to drive testis specific expression of the PP1γ isoforms. Spermatogenesis was fully restored in transgenic mice expressing PP1γ2. Significantly ~30% of mature spermatozoa were motile with normal morphology. However a small but significant proportion of sperm still retained morphological abnormities. We conclude that appropriate levels of PP1γ2 in developing germ cells and a concomitant expression of the PP1γ1 isoform in Sertoli cells are required for normal spermatogenesis, sperm morphology and motility.