Molecular Mechanisms and Signaling Pathways Involved in the Nutritional Support of Spermatogenesis by Sertoli Cells

Abstract

Sertoli cells play a central role in spermatogenesis. They maintain the blood-testis barrier, an essential feature of seminiferous tubules which creates the proper environment for the occurrence of the spermatogenesis. However, this confinement renders germ cells almost exclusively dependent on Sertoli cells' nursing function and support. Throughout spermatogenesis, differentiating sperm cells become more specialized, and their biochemical machinery is insufficient to meet their metabolic demands. Although the needs are not the same at all differentiation stages, Sertoli cells are able to satisfy their needs. In order to maintain the seminiferous tubule energetic homeostasis, Sertoli cells react in response to several metabolic stimuli, through signaling cascades. The AMP-activated kinase, sensitive to the global energetic status; the hypoxia-inducible factors, sensitive to oxygen concentration; and the peroxisome proliferator-activated receptors, sensitive to fatty acid availability, are pathways already described in Sertoli cells. These cells' metabolism also reflects the whole-body metabolic dynamics. Metabolic diseases, including obesity and type II diabetes mellitus, induce changes that, both directly and indirectly, affect Sertoli cell function and, ultimately, (dys)function in male reproductive health. Insulin resistance, increased estrogen synthesis, vascular disease, and pubic fat accumulation are examples of metabolic-related conditions that affect male fertility potential. On the other hand, malnutrition can also induce negative effects on male sexual function. In this chapter, we review the molecular mechanisms associated with the nutritional state and male sexual (dys)function and the central role played by the Sertoli cells.

Relevance of Fatty Acids to Sperm Maturation and Quality

“…For instance, the AMP-activated kinase is responsive to the global energetic status, the hypoxia-inducible factors are sensitive to oxygen concentration, and the peroxisome proliferator-activated receptors (PPARs) are influenced by FA availability in Sertoli cells. The development of metabolic diseases, including obesity and type II diabetes mellitus, induces these changes both directly and indirectly and as a consequence affects the Sertoli cell function and eventually male reproductive health [34].…”

Multiple signaling pathways in Sertoli cells: recent findings in spermatogenesis

“…The AMPK is a kind of heterotrimeric Ser/Thr kinase, which serves as the sensitive energy sensor and cellular energy metabolism regulator in Sertoli cells 19,83 . The AMPK signaling pathway in SCs has been found to regulate energy metabolism, junctional complex stability, and proliferation 84 .…”

“…Sertoli cells are the only somatic cells in the seminiferous epithelium 18 . Throughout mammalian spermatogenesis, SCs provide morphogenetic support via cell-cell interactions and also biochemical components via secreting lactate, cytokines, and hormones 19,20 . Apart from the mechanical and nutritional support, SCs also form an immune-protective environment to protect germ cells via the BTB [21][22][23][24] .…”

Spermatogenez, spermiyogenezis ve klinik yansımaları

“…[27] Sertoli hücreleri, yapısal ve biyokimyasal olarak olgunlaşan germ hücreleri için destekleyici bir ortam oluşturur. [28] Sertoli hücreleri, ayrıca germ hücreleri için testosteron bağımlı parakrin uyarıcıları salgılar. Ayrıca, FSH reseptörleri yoluyla FSH'nin de hedefindedir; böylece, Sertoli hücreleri, spermatogenezi desteklemek için testosteronun parakrin etkileri ve FSH stimülasyonu ile düzenlenmektedir.…”