Background
Fatty acid oxidation plays an important role in a variety of developing and mature organ systems. However, the role of this metabolic pathway in different stages of testis development remains unknown. Here, we elucidate the mechanisms by which fatty acid oxidation regulates the maintenance and differentiation of gonocytes and spermatogonial stem cells.
Results
During E13.5-E15.5, male germ cells gradually enter the mitotic arrest phase, while the expression of CPT1A, a rate-limiting enzyme for fatty acid oxidation, gradually increases. Therefore, we treated pregnant mice (E13.5 to E15.5) with etomoxir, which is an inhibitor of CPT1A. Etomoxir-treated mice showed no difference in embryonic morphology; however, etomoxir-treated male gonocytes exited mitotic arrest, and cells of the gonad underwent apoptosis. In addition, etomoxir-treated mice at P7 displayed impaired homing of spermatogonia and increased cell apoptosis. We further demonstrated that inhibition of fatty acid oxidation in gonads was associated with gonocyte differentiation events and the histone modification H3K27ac.
Conclusions
Inhibiting fatty acid oxidation can specifically reduce the level of H3K27ac in the reproductive crest, which may be the cause of the down-regulation of male differentiation-specific gene expression, which ultimately leads to the male primordial germ cells exited from mitotic arrest. Our work uncovers metabolic reprogramming during male gonadal development, revealing that it plays an important role in the maintenance of gonocytes in a differentiated and quiescent state during foetal testis development.
The hydroxyl groups in the amino acid residues of echinocandin B were related to the biological activity, the instability, and the drug resistance. The modification of hydroxyl groups was expected...
Marine natural products (MNPs) are an important source of biologically active metabolites, particularly for therapeutic agent development after terrestrial plants and nonmarine microorganisms. Sequencing technologies have revealed that the number of biosynthetic gene clusters (BGCs) in marine microorganisms and the marine environment is much higher than expected. Unfortunately, the majority of them are silent or only weakly expressed under traditional laboratory culture conditions. Furthermore, the large proportion of marine microorganisms are either uncultivable or cannot be genetically manipulated. Efficient heterologous expression systems can activate cryptic BGCs and increase target compound yield, allowing researchers to explore more unknown MNPs. When developing heterologous expression of MNPs, it is critical to consider heterologous host selection as well as genetic manipulations for BGCs. In this review, we summarize current progress on the heterologous expression of MNPs as a reference for future research.
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