Endocrine Abstracts

Background: Down syndrome (DS) is caused by the triplication of chromosome 21, and it is considered one of the most common chromosomal abnormalities. The genetic overload leads to several endocrine irregularities, including early onset of obesity and diabetes, hypothyroidism, and reduced fertility. While the onset and progression of puberty is similar to that of the general population, fertility, particularly in males, has been reported to be reduced in individuals with DS. Here we aim to investigate possible mechanisms behind the reduced fertility using a mouse model of DS.

Methods: The Dy1Tyb mouse strain has an extra copy of 63% of Hsa21-orthologous mouse genes and was used as our in vivo model of DS. Breeding data from Dy1Tyb colony was obtained from our in-house animal facility management system database and compared to wild-type (C57BL/6J) public data from the Mouse Phenome Database (Jackson Laboratory). Animals were sacrificed at 30 weeks of age. Gonads were weighed, and then stained with hematoxylin and eosin and analysed with QuPath software. Plasma hormones and markers involved in fertility and sexual maturation were analysed by ELISA and RT-qPCR.

Results: Male and female Dy1Tyb breeders (crossed with wild-type mice) produced fewer litters per dam, with fewer pups per litter, compared to wild-type breeders. Interestingly, female mutants showed a trend of producing less litters with smaller litter sizes compared to male mutants. The ovaries of female Dp1Tyb mice were similar in weight to that of wild-type, but showed fewer antral follicles and corpus lutea. In contrast, the testicles from Dp1Tyb males showed significantly reduced weight compared to WT, but similar morphology.

Conclusion: Our data shows that Dy1Tyb animals replicate the phenotype seen in the human population with lower fertility observed in both sexes, suggesting that this would be a good model to investigate mechanisms of infertility in DS.