Files and links (1)
PDFOpen Access (License Unspecified), Open Access
Thesis
The role of CHTF18 in male meiotic cohesion
Master of Science (M.S.), Drexel University
May 2022
DOI:
https://doi.org/10.17918/00002029
Abstract
Male factor is the primary cause of infertility in 20% of infertile couples. At least 70% of male infertility is attributed to primary testicular defects in spermatogenesis. However, the majority of these defects do not have an identifiable etiology. Thus, the defects underlying male infertility remain largely unknown. Chromosome cohesion during mitosis and meiosis is a process established and maintained by the cohesin complex that ensures accurate chromosome segregation and, ultimately, safeguards spermatogenesis. Recently, we showed that CHTF18, a component of the conserved Replication Factor C-like complex, CHTF18-RFC, plays a role in chromosome cohesion in mammalian meiosis. Currently, we investigated the role of CHTF18 in male meiotic cohesion. We showed that CHTF18 physically interacts with mitotic and meiotic cohesins and that chromatin-associated cohesins are decreased in Chtf18-/- testis extracts. We validated these results cytologically by showing that chromosome-associated meiotic cohesins are decreased in Chtf18-/- spermatocytes. CHTF18 also appears to regulate levels of salt sensitive chromatin-associated meiotic cohesins, suggesting that CHTF18 stabilizes cohesins on chromatin during meiosis. In addition to structural cohesins, chromatin-associated cohesin accessory proteins implicated in cohesin loading (NIPBL), cohesion establishment (PDS5B), and cohesin release (WAPL) are also decreased in Chtf18-/- testis extracts. Therefore, we investigated chromosome-associated levels of these accessory proteins in spermatocytes. Collectively, our results and preliminary findings suggest that CHTF18 regulates meiotic cohesins via accessory proteins. Overall, these data reveal a role for CHTF18 in mediating meiotic cohesion, which could ultimately impact diagnosis and treatment of male infertility.
Metrics
20 File views/ downloads
24 Record Views
Details
- Title
- The role of CHTF18 in male meiotic cohesion
- Creators
- Bridget Ryan
- Contributors
- Karen M. Berkowitz (Advisor) - Drexel University, MD (Doctor of Medicine) Program
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- viii, 64 pages
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; College of Medicine; Drexel University
- Other Identifier
- 991020504715704721