Morphological and transcriptomic alterations in neonatal lamb testes following developmental exposure to low-level environmental chemical mixture

Abstract

Exposure to anthropogenic environmental chemical mixtures could be contributing to the decline in male reproductive health. This study used the biosolid treated pasture (BTP) sheep model to assess the effects of exposure to low-dose chemical mixtures. Maternal BTP exposure was associated with lower plasma testosterone concentrations, a greater proportion of Sertoli cell-only seminiferous tubules, and fewer gonocytes in the testes of neonatal offspring. Transcriptome analysis highlighted changes in testicular mTOR signalling, including lower expression of two mTOR complex components. Transcriptomic hierarchical analysis relative to the phenotypic severity demonstrated distinct differential responses to maternal BTP exposure during pregnancy. Transcriptome analysis between phenotypically normal and abnormal BTP lambs demonstrated separate responses within the cAMP and PI3K signalling pathways towards CREB. Together, the results provide a potential mechanistic explanation for adverse effects. Exposure could lower gonocyte numbers through mTOR mediated autophagy, but CREB mediated survival factors may act to increase germ cell survival.

Keywords: Developmental toxicity; Environmental chemicals; Testicular dysgenesis syndrome.