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Dissertation
SERTOLI CELL DYNAMICS ACROSS THE CYCLE OF THE SEMINIFEROUS EPITHELIUM
Washington State University
Doctor of Philosophy (PhD), Washington State University
05/2025
DOI:
https://doi.org/10.7273/000007381
Abstract
Sertoli cells, omnipresent, somatic cells within the seminiferous tubules of the mammalian testis are essential to male fertility. Sertoli cells maintain the integrity of the testicular
microenvironment, regulate hormone synthesis, and of particular importance, synthesize the active derivative of vitamin A, all-trans retinoic acid (atRA), which is required for germ cell differentiation and the commitment of male germ cells to meiosis. Stages VIII-IX, when atRA synthesis occurs in the testis, coincides with multiple developmental and testicular restructuring events that rely on Sertoli cell gene products to proceed normally. Through this work, we have sought to elucidate the molecular drivers that regulate Sertoli cell behaviors during stages VIII-IX and expand our knowledge on proposed Sertoli cell products. We have synchronized and captured murine testes at four recurrent points of atRA synthesis to observe transcriptomic changes within Sertoli cells as the testicular microenvironment is exposed to increasingly developed germ cell subtypes. These experiments provided comprehensive, high-resolution characterization of when known, functional Sertoli cell genes are induced across the first wave of spermatogenesis, along with in silico predictions of germ cell derived signaling mechanisms targeting Sertoli cells. From these predictions, we have started investigations into the Notch signaling pathway as a potential driver of germ-Sertoli cell signaling by generating a germ cell specific conditional knockout mouse model of delta like non-canonical Notch ligand 1 (Dlk1) and evaluating the affected transcriptome of the Sertoli cells and germ cells prior to, and after, the “A to A1 transition” as induced by atRA treatment. From this work we have found evidence that Dlk1 regulates testicular Notch signaling during early postnatal development, and controls Sertoli cell proliferation, and may regulate germ cell differentiation. Finally, we have identified several potential Sertoli cell cytoskeletal proteins by evaluating the RNA and protein expression of several actin bundling and myosin-protein coding genes at a cell- and stage-specific resolution. Based on the specific expression observed through immunohistochemical analysis, we predict that these proteins may predominantly act to facilitate the formation and maintenance of Sertoli-germ cell adherent junctions and the blood-testis barrier and may play a role in mitotic and meiotic germ cell division. Together, this work has provided previously unseen resolution into the expression patterns of stage VIII-IX Sertoli cells, and the dynamics of germ-Sertoli cell communication, throughout spermatogenesis.
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Details
- Title
- SERTOLI CELL DYNAMICS ACROSS THE CYCLE OF THE SEMINIFEROUS EPITHELIUM
- Creators
- Shelby Lee Havel
- Contributors
- Michael Griswold (Chair)James MacLean II (Committee Member)Nathan Law (Committee Member)Erika Offerdahl (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- School of Molecular Biosciences
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Publisher
- Washington State University
- Number of pages
- 185
- Identifiers
- 99901220448801842
- Language
- English
- Resource Type
- Dissertation