Metabotropic glutamate receptors (mGluRs) are best known for modulating synaptic transmission, yet accumulating evidence shows that they are also widely expressed in peripheral tissues, including the testis. Methodologically, this work integrates a narrative synthesis of the literature with an in-silico bioinformatic analysis of bulk (GTEx) and single-cell (HPA, CellxGene) RNA-seq datasets, aiming to clarify how mGluRs contribute to testicular physiology. After outlining the striking structural and metabolic parallels between brain and testis—tight barrier systems, selenium-dependent redox control, and exceptionally complex alternative splicing—we confirm that several mGluR subtypes are expressed in Sertoli, Leydig, and germ cells. GRM7 and GRM8 emerge as the dominant transcripts during the late stages of spermatogenesis, and their co-expression networks are strongly linked to axoneme assembly, cilium-driven motility, mitogen-activated protein kinase (MAPK) signaling, and spermatid differentiation. These results point to a role for mGluR-dependent, cyclic adenosine monophosphate (cAMP)-sensitive pathways in fine-tuning sperm maturation and motility. We further discuss how mGluR activity interfaces with the hypothalamic– pituitary–gonadal (HPG) axis and local estrogen signaling, highlighting implications for male infertility, novel contraceptive strategies, and the safe therapeutic targeting of mGluRs in neuropsychiatry. Overall, the data reinforce the concept of a brain–testis continuum, in which glutamatergic signaling is pivotal not only to neuronal plasticity but also to spermatogenesis, steroidogenesis, and sperm function. • Brain and testis share convergent metabolic, barrier, and redox architectures. • Group III metabotropic glutamate receptors (mGlu7/mGlu8) are expressed in human germ cells. • Bioinformatic network analyses link GRM7/GRM8 to axonemal assembly and motility. • mGluR-mediated cAMP and MAPK pathways integrate endocrine and metabolic cues. • Implications arise for reproductive safety of CNS-targeting drugs and novel contraceptive approaches.
Barlattani et al. (Fri,) studied this question.