2026-09-18T19:34:27Zhttps://dspace.mit.edu/server/oai/requestoai:dspace.mit.edu:1721.1/409542022-01-13T07:54:15Zcom_1721.1_7582com_1721.1_7581col_1721.1_131022
David C. Page.
Koubová, Jana C
Massachusetts Institute of Technology. Dept. of Biology.
Massachusetts Institute of Technology. Department of Biology
2008-03-27T18:28:08Z
2008-03-27T18:28:08Z
2007
2007
http://hdl.handle.net/1721.1/40954
212907400
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2007.
Includes bibliographical references.
Germ cells are the only cell type to undergo meiosis, a specialized cell division process necessary for the formation of haploid gametes. Timing of this process is sex-specific. Ovarian germ cells initiate meiosis during embryonic development, while testicular germ cells initiate meiosis after birth. In a series of gonad explant culture experiments, I show that retinoic acid (RA) is required for meiotic initiation in embryonic ovaries, because it is necessary for Stra8 (Stimulated by retinoic acid gene 8) expression. Stra8 is required for pre-meiotic DNA replication in embryonic ovaries and it is only expressed in testes after birth. I also show that a cytochrome p450 enzyme CYP26B 1, specifically expressed in embryonic testes but not ovaries, prevents Stra8 expression in testes during embryonic development. To confirm our results in vivo, and to examine if RA is sufficient to induce meiosis in embryonic testes, I generated Cyp26bl-/- and Cyp26bl-/-Stra8-/- mice. I show that germ cells in Cyp26bl-/- embryonic testes initiate a meiotic program but fail to complete meiotic prophase. Instead, germ cells proliferate until birth. RA also causes somatic cell defects. It inhibits Leydig cell differentiation and disturbs testis cord maintenance. Thus, RA has distinct effects in embryonic ovaries and embryonic testes. In ovaries, it is required for meiotic entry with no known effects on somatic cell development. In embryonic testes, RA is not sufficient for functional meiotic prophase and it induces proliferation in germ cells. RA also disrupts embryonic testicular somatic cell development.
by Jana C. Koubova.
Ph.D.
321 leaves
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 retinoic acid in germ cell development in embryonic mouse gonads
Role of RA in germ cell development in embryonic mouse gonads
Thesis
application/pdf
false
Publication
unknown
unknown
<Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="d0e68da3-ab69-415f-ae15-f42a0cc075a3">
<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 retinoic acid in germ cell development in embryonic mouse gonads</Title>
<Subtitle>Role of RA in germ cell development in embryonic mouse gonads</Subtitle>
<PublishedIn>
<Publication>
</Publication>
</PublishedIn>
<PublicationDate>2007</PublicationDate>
<Authors>
<Author>
<DisplayName>Koubová, Jana C</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>Germ cells are the only cell type to undergo meiosis, a specialized cell division process necessary for the formation of haploid gametes. Timing of this process is sex-specific. Ovarian germ cells initiate meiosis during embryonic development, while testicular germ cells initiate meiosis after birth. In a series of gonad explant culture experiments, I show that retinoic acid (RA) is required for meiotic initiation in embryonic ovaries, because it is necessary for Stra8 (Stimulated by retinoic acid gene 8) expression. Stra8 is required for pre-meiotic DNA replication in embryonic ovaries and it is only expressed in testes after birth. I also show that a cytochrome p450 enzyme CYP26B 1, specifically expressed in embryonic testes but not ovaries, prevents Stra8 expression in testes during embryonic development. To confirm our results in vivo, and to examine if RA is sufficient to induce meiosis in embryonic testes, I generated Cyp26bl-/- and Cyp26bl-/-Stra8-/- mice. I show that germ cells in Cyp26bl-/- embryonic testes initiate a meiotic program but fail to complete meiotic prophase. Instead, germ cells proliferate until birth. RA also causes somatic cell defects. It inhibits Leydig cell differentiation and disturbs testis cord maintenance. Thus, RA has distinct effects in embryonic ovaries and embryonic testes. In ovaries, it is required for meiotic entry with no known effects on somatic cell development. In embryonic testes, RA is not sufficient for functional meiotic prophase and it induces proliferation in germ cells. RA also disrupts embryonic testicular somatic cell development.</Abstract>
<Access xmlns="http://purl.org/coar/access_right"
>
</Access>
</Publication>