Dissertation
SOURCES OF RETINOIC ACID SYNTHESIS AND HISTONE MODIFICATIONS DURING POSTNATAL TESTIS DEVELOPMENT
Doctor of Philosophy (PhD), Washington State University
01/2018
Handle:
https://hdl.handle.net/2376/111253
Abstract
The importance of all-trans-retinoic acid (at-RA; hereafter referred to as RA) in normal sperm production has been recognized for many years. Consistent with this, an excess or deficiency of RA results in a range of male reproductive abnormalities. It has been widely postulated that the aldehyde dehydrogenase 1A (ALDH1A) family of enzymes, specifically the isozyme ALDH1A2 residing within the meiotic and post-meiotic germ cells, are responsible for RA synthesis after the first round of spermatogenesis. However, the studies presented within this dissertation demonstrate that the genetic elimination of ALDH1A2 is not sufficient to arrest spermatogenesis. Surprisingly the potent inhibition of the ALDH1A enzyme family (i.e. ALDH1A1, ALDH1A2, and ALDH1A3) after a single RA injection was not able to immediately arrest spermatogenesis. We identified the aldehyde oxidases as potential contributors to RA synthesis, thus compensating for the loss of ALDH1A enzymes within experimental testes. Collectively, these results suggest that an additional source of RA synthesis exists in the postnatal testis. Additionally, a large number of testis-specific histone variants have been identified, however little is known about the role that these variants play during male germ cell development. Unpublished studies in our laboratory suggest that two histone variants, Hist1h2b (TH2B) and Hist1h2a (TH2A), may be differentially expressed between the first round and subsequent rounds of spermatogenesis. To test this, we employed a unique double immunofluorescence protocol to illustrate that TH2B and TH2A are localized to the undifferentiated spermatogonia within the neonatal testis. However, once the first preleptotene spermatocytes appear, we identified a unique switch in the expression of TH2B from the undifferentiated spermatogonia to the spermatocyte population. These studies contribute to the growing body of evidence demonstrating that spermatogonia within the neonate are epigenetically distinct from spermatogonia residing within the adult.
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Details
- Title
- SOURCES OF RETINOIC ACID SYNTHESIS AND HISTONE MODIFICATIONS DURING POSTNATAL TESTIS DEVELOPMENT
- Creators
- My-Thanh Beedle
- Contributors
- Michael Griswold (Advisor)Wipawee Winuthayanon (Committee Member)Jon Oatley (Committee Member)John Wyrick (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Molecular Biosciences, School of
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Number of pages
- 209
- Identifiers
- 99900581424501842
- Language
- English
- Resource Type
- Dissertation