Mutant phenotype analysis suggests potential roles for C-type natriuretic peptide receptor (NPR-B) in male mouse fertility

Background: C-type natriuretic peptide (CNP) signaling through its receptor natriuretic peptide receptor B (NPR-B) is a key molecule for mammalian reproduction, and known to play important roles in female fertility. However, the function of these peptides in mouse male reproduction remains largely unknown. To determine the role of CNP/NPR-B signaling in male reproduction we investigated phenotype of Npr2-deficient short-limbed-dwarfism (Npr2^slw/slw) mice, which have been shown to have gastrointestinal (GI) abnormalities.Findings: In homozygous Npr2^slw/slw mice, spermatogenesis is developmentally delayed at both 2 and 4 weeks of age, with vacuolation and degenerating apoptotic germ cells being observed at 3 weeks age. However, the adult Npr2^slw/slw mice exhibited apparently normal spermatogenesis, albeit with some aberrant spermatids, suggesting that developmental delay was overcome. In addition, the adult Npr2^slw/slw mice showed abnormal penile morphology (paraphimosis).Conclusions: The potential role of CNP signaling via the NPR-B receptor in male fertility appears to be mediated not through germ-cell development, but may be through maintenance of normal penile function.