Most mammalian species of the temperate zones of the Earth reproduce seasonally, existing a non-breeding period in which the gonads of both sexes undergo functional regression. It is widely accepted that photoperiod is the principal environmental cue controlling these seasonal changes, although several exceptions have been described in other mammalian species in which breeding depends on cues such as food or water availability. We studied the circannual reproductive cycle in males of the Mediterranean pine vole, Microtus duodecimcostatus, in the Southeastern Iberian Peninsula. Morphological, hormonal, functional, molecular and transcriptomic analyses were performed. As reported for populations of other species from the same geographic area, male voles captured in wastelands underwent seasonal testis regression in summer whereas, surprisingly, those living either in close poplar plantations or in our animal house reproduced throughout the year, showing that it is the microenvironment of a particular vole subpopulation what determines its reproductive status and that these animals are pure opportunistic, photoperiod-independent breeders. In addition, we show that several molecular pathways, including MAPK, are deregulated and that the testicular “immune privilege” is lost in the inactive testes, providing novel mechanisms linking seasonal testosterone reduction and testis regression.

In most mammals with seasonal reproduction, males undergo testis regression during the non-breeding period. We performed a morphological, hormonal, functional, and molecular study of the testes of sexually inactive males of two species of murine rodents, the wood mouse, Apodemus sylvaticus, and the Algerian mouse, Mus spretus, in syntopic populations of southern Iberian peninsula. Both species reproduce during most of the year, but wood mice stop breeding in the summer whereas Algerian mice do it in winter. Sexually inactive males of A. sylvaticus show complete testis regression with reduced levels of serum testosterone and abnormal distribution of cell-adhesion molecules. Contrarily, inactive males of M. spretus maintain almost normal spermotogenesis despite a significant reduction of androgenic function. The lack of an evident explanation for the divergent seasonal breeding patterns found in southern populations of A. sylvaticus and M. spretus, compared with northern ones, implies that very subtle species/population-specific features and/or non-conspicuous environmental cues probably operate to determine their seasonal breeding pattern. These results also support the notion that multiple models of circannual testis variation are possible for different populations of the same species, showing that the mechanisms controlling seasonal reproduction are in fact very plastic and fast evolving.

Testes of seasonally breeding species experience a severe functional regression before the non-breeding period, which implies a substantial mass reduction due to massive germ-cell depletion. Two alternative mechanisms of seasonal germ-cell depletion have been described in mammals, apoptosis and desquamation (sloughing), but their prevalence has not been determined yet due to reduced number of species studied. We performed a morphological, hormonal, and molecular study of the mechanism of seasonal testicular regression in males of the Egyptian long eared-hedgehog (Hemiechinus auritus). Our results show that live, non-apoptotic, germ cells are massively depleted by desquamation during the testis regression process. This is concomitant with both decreased levels of serum testosterone and irregular distribution of the cell-adhesion molecules in the seminiferous epithelium. The inactive testes maintain some meiotic activity as meiosis onset is not halted and spermatocytes die by apoptosis at the pachytene stage. Our data support the notion that apoptosis is not the major testis regression effector in mammals. Instead, desquamation appears to be a common mechanism in this class.

In species with seasonal breeding, male specimens undergo substantial testicular regression during the non-breeding period of the year. However, the molecular mechanisms that control this biological process are largely unknown. Here, we report a transcriptomic analysis on the Iberian mole, Talpa occidentalis, in which the desquamation of live, non-apoptotic germ cells is the major cellular event responsible for testis regression. By comparing testes at different reproductive states (active, regressing and inactive), we demonstrate that the molecular pathways controlling the cell adhesion function in the seminiferous epithelium, such as the MAPK, ERK and TGF-beta signalling, are altered during the regression process. In addition, inactive testes display a global upregulation of genes associated with immune response, indicating a selective loss of the immune privilege that normally operates in sexually active testes. Interspecies comparative analyses using analogous data from the Mediterranean pine vole, a rodent species where testis regression is controlled by halting meiosis entry, revealed a common gene expression signature in the regressed testes of these two evolutionary distant species. Our study advances in the knowledge of the molecular mechanisms associated to gonadal seasonal breeding, highlighting the existence of a conserved transcriptional program of testis involution across mammalian clades.

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