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David C. Page. Anderson, Ericka L. (Ericka Lynne) Massachusetts Institute of Technology. Dept. of Biology. Massachusetts Institute of Technology. Department of Biology 2011-08-16T15:24:30Z 2011-08-16T15:24:30Z 2010 2011 http://hdl.handle.net/1721.1/65168 744980869 Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2011. This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. Cataloged from student submitted PDF version of thesis. Includes bibliographical references (p. 124-129). Spermatogenesis is a highly regulated, cyclical process where sperm are constantly produced. Previous work characterizing male rodents maintained on a Vitamin A Deficient diet has demonstrated that retinoic acid (RA) governs two transitions during mammalian spermatogenesis. These germ cell transitions include the transition from undifferentiated spermatogonia to differentiating spermatogonia, which continue to proliferate mitotically, and the transition from mitosis to meiosis. This work led to questions about the mechanisms through which RA governs these transitions. Here I will present my findings demonstrating that Stra8, previously demonstrated to be a RA-induced gene, is a target gene of RA in both the transition from undifferentiated spermatogonia to differentiating spermatogonia and the transition from mitosis to meiosis. I conclude that RA inducing Stra8 is the mechanism that regulates these developmental transitions. The architecture of germ cell development in the rodent testis is such that these two RA-governed transitions occur in immediate physical proximity, suggesting the possibility that the RA inducing Stra8 mechanism could regulate both transitions simultaneously. I conclude that this mechanism could play a part in the regulation of the seminiferous cycle during spermatogenesis. In the appendices I will also present my findings that demonstrate Stra8 functions in testicular germ cell tumors. I conclude that Stra8 function in the transition from undifferentiated spermatogonia to differentiating spermatogonia acts as a tumor suppressor for seminoma tumors. In contrast, I find that Stra8 is required for testicular teratomas to form, indicating a role for Stra8 in the formation of these tumors. by Ericka L. Anderson. Ph.D. 129 p. eng Massachusetts Institute of Technology M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 Biology. The Role of Stra8 in spermatogenesis : regulation of spermatogonial differentiation, meiotic initiation, and testicular tumor formation Thesis application/pdf false Publication unknown unknown <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="5997ae8c-adf9-4fcf-a2f4-450546f8f460"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Language>eng</Language> <Title>The Role of Stra8 in spermatogenesis : regulation of spermatogonial differentiation, meiotic initiation, and testicular tumor formation</Title> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2011</PublicationDate> <Authors> <Author> <DisplayName>Anderson, Ericka L. (Ericka Lynne)</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Massachusetts Institute of Technology</DisplayName> <OrgUnit /> </Publisher> </Publishers> <License>http://dspace.mit.edu/handle/1721.1/7582</License> <Keyword>Biology.</Keyword> <Abstract>Spermatogenesis is a highly regulated, cyclical process where sperm are constantly produced. Previous work characterizing male rodents maintained on a Vitamin A Deficient diet has demonstrated that retinoic acid (RA) governs two transitions during mammalian spermatogenesis. These germ cell transitions include the transition from undifferentiated spermatogonia to differentiating spermatogonia, which continue to proliferate mitotically, and the transition from mitosis to meiosis. This work led to questions about the mechanisms through which RA governs these transitions. Here I will present my findings demonstrating that Stra8, previously demonstrated to be a RA-induced gene, is a target gene of RA in both the transition from undifferentiated spermatogonia to differentiating spermatogonia and the transition from mitosis to meiosis. I conclude that RA inducing Stra8 is the mechanism that regulates these developmental transitions. The architecture of germ cell development in the rodent testis is such that these two RA-governed transitions occur in immediate physical proximity, suggesting the possibility that the RA inducing Stra8 mechanism could regulate both transitions simultaneously. I conclude that this mechanism could play a part in the regulation of the seminiferous cycle during spermatogenesis. In the appendices I will also present my findings that demonstrate Stra8 functions in testicular germ cell tumors. I conclude that Stra8 function in the transition from undifferentiated spermatogonia to differentiating spermatogonia acts as a tumor suppressor for seminoma tumors. In contrast, I find that Stra8 is required for testicular teratomas to form, indicating a role for Stra8 in the formation of these tumors.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>