GIPR gene expression in testis is mouse specific and can impact male mouse fertility

Glucose-dependent insulinotropic polypeptide receptor (Gipr) gene expression has been reported in mouse spermatids and Gipr knockout male mice have previously been reported to have decreased in vitro fertilization, although the role of Gipr signaling in male mouse fertility is not well understood.

The purposes of these studies were to determine the role of glucose-dependent insulinotropic polypeptide receptor in male fertility using Gipr knockout mice and anti-glucose-dependent insulinotropic polypeptide receptor antibody-treated wild-type mice and to determine if the expression of Gipr in mouse testes is similar in non-human and human primates.

Adiponectin promoter-driven Gipr knockout male mice (Gipr^Adipo-/- ) were assessed for in vitro and in vivo fertility, sperm parameters, and testicular histology. CD1 male mice were administered an anti-glucose-dependent insulinotropic polypeptide receptor antibody (muGIPR-Ab) prior to and during mating for assessment of in vivo fertility and sperm parameters. Expression of Gipr/GIPR mRNA in the mouse, cynomolgus monkey, and human testes was assessed by in situ hybridization methods using species-specific probes.

Gipr^Adipo-/- male mice are infertile in vitro and in vivo, despite normal testis morphology, sperm counts, and sperm motility. In contrast, administration of muGIPR-Ab to CD1 male mice did not impact fertility. While Gipr mRNA expression is detectable in the mouse testes, GIPR mRNA expression is not detectable in monkey or human testes.

The infertility of Gipr^Adipo-/- male mice correlated with the lack of Gipr expression in the testis and/or adipocyte tissue. However, as administration of muGIPR-Ab did not impact the fertility of adult male mice, it is possible that the observations in genetically deficient male mice are related to Gipr deficiency during development.

Our data support a role for Gipr expression in the mouse testis during the development of sperm fertilization potential, but based on gene expression data, a similar role for glucose-dependent insulinotropic polypeptide receptor in non-human primate or human male fertility is unlikely.