Research Info

Background: Numerous factors intricately regulate the metabolism of Sertoli cells and sperm, with sex steroid hormones emerging as a pivotal player. These hormones not only maintain energy homeostasis but also wield considerable influence over the metabolic equilibrium of the human body. Given the critical role of energy status in reproductive function, understanding its regulation is paramount, as the reproductive axis demonstrates responsiveness to metabolic cues. Methods: To delve into this intricate interplay, advanced methodologies such as microarray and bioinformatics were employed. These techniques shed light on the activity of metabolite interconversion enzymes within the context of 200 genes expressed in sperm and Sertoli cells. Results: In sperm, heightened expression of monooxygenase DBH like 1 (MOXD1) and cytochrome P450 family 46 subfamily A member 1 (CYP46A1) was observed, juxtaposed with decreased expression of arginine decarboxylase (ADC) and cytochrome b5 type B (C0YB5B). Conversely, Sertoli cells from individuals with non-obstructive azoospermia (NOA) exhibited upregulation in RPIA, PIK3C3, LYPLA2, and HDHD2 expression, while a slew of genes—including L2HGDH, GALNTL2, OXCT1, GSTT2, HSD17B7, PDPR, SESN1, ESCO2, SYNJ2, EBPL, DHFR, SORD, and CES1—showed downregulation. To unravel the functional and molecular networks underlying these changes, STRING and Cytoscape online assessments were employed. They revealed intricate connections among proteins and helped identify master genes. Notably, G1/S-specific transcription, pyruvate and citric acid metabolism, and alkylation damage caused by DNA dioxygenases emerged as primary molecular functions of the up/down-regulated genes in sperm. In Sertoli cells, folate metabolism and the p53 signaling pathway took precedence. Conclusion: Validation of these findings through weighted gene co-expression network analysis and single-cell data corroborated the observed changes in gene expression patterns. Collectively, t