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A Seminiferous Tubule Squash Technique for the Cytological Analysis of Spermatogenesis Using the Mouse Model
Published on: February 6, 2018
Mouse Pramel1 regulates spermatogonial development by inhibiting retinoic acid signaling during spermatogenesis
Mingyao Yang1, Wenzhi Ma1, Jon Oatley2
1Department of Animal Science, Center for Reproductive Biology and Health (CRBH), College of Agricultural Sciences, The Pennsylvania State University,University Park, PA 16803, USA.
Abstract:
Spermatogenesis begins when cell fate-committed prospermatogonia migrate to the basement membrane and initiate spermatogenesis in response to retinoic acid (RA) in the neonatal testis. The underlying cellular and molecular mechanisms in this process are not fully understood. Here, we report findings on the involvement of a cancer/testis antigen, PRAMEL1, in the initiation and maintenance of spermatogenesis. By analyzing mouse models with either global or conditional Pramel1 inactivation, we found that PRAMEL1 regulates the RA responsiveness of the subtypes of prospermatogonia in the neonatal testis, and affects their homing process during the initiation of spermatogenesis. Pramel1 deficiency led to increased fecundity in juvenile males and decreased fecundity in mature males. In addition, Pramel1 deficiency resulted in a regional Sertoli cell-only phenotype during the first round of spermatogenesis, which was rescued by administration of the RA inhibitor WIN18,446, suggesting that PRAMEL1 functions as an inhibitor of RA signaling in germ cells. Overall, our findings suggest that PRAMEL1 fine-tunes RA signaling, playing a crucial role in the proper establishment of the first and subsequent rounds of spermatogenesis.
Insights
The cancer/testis antigen PRAMEL1 regulates retinoic acid (RA) signaling during the initiation of spermatogenesis. PRAMEL1 fine-tuning of RA signaling is crucial for proper sperm development and male fertility.
Area of Science:
- Reproductive biology
- Developmental biology
- Molecular endocrinology
Background:
- Spermatogenesis initiation involves prospermatogonia migration and retinoic acid (RA) signaling.
- The precise molecular mechanisms governing RA responsiveness and germ cell homing are not fully elucidated.
- Cancer/testis antigens are implicated in reproductive processes, but their roles in spermatogenesis require further investigation.
Purpose of the Study:
- To investigate the role of the cancer/testis antigen PRAMEL1 in the initiation and maintenance of spermatogenesis.
- To determine how PRAMEL1 influences retinoic acid (RA) signaling and germ cell behavior in the neonatal testis.
- To understand the impact of PRAMEL1 deficiency on male reproductive function and fertility.
Main Methods:
- Analysis of global and conditional Pramel1-inactivated mouse models.
- Assessment of prospermatogonia homing and RA responsiveness in neonatal testes.
- Evaluation of fecundity in juvenile and mature male mice with Pramel1 deficiency.
- Investigation of the effects of RA inhibition (WIN18,446) on Pramel1-deficient phenotypes.
Main Results:
- PRAMEL1 regulates RA responsiveness and homing of prospermatogonia during spermatogenesis initiation.
- Pramel1 deficiency leads to altered fecundity: increased in juveniles, decreased in mature males.
- Pramel1 deficiency causes a regional Sertoli cell-only phenotype, which is reversible with RA inhibition.
- PRAMEL1 acts as an inhibitor of RA signaling in germ cells.
Conclusions:
- PRAMEL1 plays a critical role in fine-tuning RA signaling essential for establishing spermatogenesis.
- PRAMEL1 is vital for the proper initiation and maintenance of both the first and subsequent rounds of spermatogenesis.
- Understanding PRAMEL1's function provides insights into male reproductive health and potential therapeutic targets.
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