The Effect of Transient Neonatal Goitrogen Exposure on Akt1-Dependent Testicular Development and Gene Expression in the C57/Bl6 Mouse

Santos Ahmed, Jeena M.

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Year:: 2011
Contributor:: Santos Ahmed, Jeena M (creator); Hixon, Mary (Director); Boekelheide, Kim (Reader); Freiman, Richard (Reader); Messerlian, Geralyn (Reader); Gilbert, Mary (Reader); Brown University. BIOMED: Pathobiology (sponsor)
Genre:: theses
Subject:: Akt; Hypothyroid,Sertoli,Claudin; Testis
Extent:: ix, 124 p.
DOI: https://doi.org/10.7301/Z04Q7S89

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Abstract:: The Sertoli cell is the "support cell" of the testis. The number of Sertoli cells which populate the testis during peri-pubertal development dictate the number of germ cells that can be supported within the adult testis. Therefore, Sertoli cell and germ cell proliferation, differentiation, and communication are tantamount to normal testis development. Multiple signaling cascades exist within the testis to coordinate the proliferation and differentiation of both Sertoli cells and germ cells. The Akt gene family is one important signaling pathway implicated in testis growth and development. Our previous work has shown that Akt1-deficient testes are more sensitive than their wild type counterparts to both germ and Sertoli cell toxicants. Based on this information, we hypothesize that Akt1 plays a role in the promotion of Sertoli cell proliferation/ maturation following peri-pubertal exposure to a thyroid disrupting chemical. Previous studies have demonstrated that peri-pubertal Sertoli cell proliferation is also regulated by thyroid hormone. Transient neonatal hypothyroidism induced by exposure to the neonatal goitrogen, 6-N-propylthiouracil (PTU) prolongs Sertoli cell proliferation and differentiation. An increase in Sertoli cell number leads to an increase in germ cell number and a subsequent increase in adult testis size. We hypothesize that altered spermatogenesis due to endocrine disrupting thyroid toxicants may partially reflect changes in the normal function of the Sertoli cell population due to their effect of extending the period of Sertoli cell proliferation and/or delaying Sertoli cell maturation. This hypothesis is based on the following observations: first, our data indicate that the Akt1 signaling pathway mediates peri-pubertal testis growth and fertility following lactational exposure to PTU, and second, gene expression and bioinformatic analyses revealed that PTU targets proteins of testicular tight junctions, including several members of the claudin gene family. Our aims were designed to provide a comprehensive assessment of signaling pathways associated with thyroid toxicant-induced Sertoli cell injury. Specifically, we characterized the impact of the Sertoli cell toxicant, PTU, on postnatal development of the testis and to begin to identify the signaling networks targeted by thyroid toxicant-induced peri-pubertal testicular injury.
Notes:: Thesis (Ph.D. -- Brown University (2011)

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Rights: In Copyright
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Santos Ahmed, Jeena M., "The Effect of Transient Neonatal Goitrogen Exposure on Akt1-Dependent Testicular Development and Gene Expression in the C57/Bl6 Mouse" (2011). Pathobiology Theses and Dissertations. Brown Digital Repository. Brown University Library. https://doi.org/10.7301/Z04Q7S89

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Pathobiology Theses and Dissertations

Theses and Dissertations for the Pathobiology department.
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