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Updated: Aug 19, 2026

Quantitative Analysis of Dietary Vitamin A Metabolites in Murine Ocular and Non-Ocular Tissues Using High-Performance Liquid Chromatography
Published on: December 27, 2024
The administration of retinoic acid down-regulates cAMP-responsive element modulator (CREM) mRNA in vitamin
Mami Matsuda1, Tomomasa Hyoudou, Masanori Kadowaki
1Department of Agricultural Chemistry, Faculty of Agriculture, Tokyo University of Agriculture, Tokyo, Japan.
Abstract:
Studies using genetics and vitamin A deficiency (VAD) have shown that vitamin A and retinoids play essential roles in spermatogenesis at the pre-meiotic stage. To understand the mechanisms of control in spermatogenesis by retinoic acid, we investigated whether retinoic acids regulate the expression of downstream transcription factors that are essential for spermatogenesis. In this study, we found that administration of all-trans retinoic acid (ATRA) or retinol to VAD rats down-regulates the testicular mRNA levels of the cAMP responsive element modulator (CREM), an essential transcription factor for spermatogenesis. Conversely, depletion of retinoids from the diet leds to an up-regulation of CREM expression in adult testes. In addition, RT-PCR analysis indicated that ATRA specifically represses the expression of the activator spliced variant of CREM (CREMtau). These results suggest that retinoids function as a negative regulator of CREM expression in testes.
Insights
Retinoids, essential for sperm development, negatively regulate the expression of the transcription factor CREM (cAMP responsive element modulator). Vitamin A deficiency increases CREM levels, impacting spermatogenesis.
Area of Science:
- Reproductive biology
- Molecular endocrinology
- Spermatogenesis research
Background:
- Vitamin A and its derivatives (retinoids) are crucial for male reproductive functions, particularly spermatogenesis.
- The precise molecular mechanisms by which retinoids regulate spermatogenesis remain incompletely understood.
Purpose of the Study:
- To investigate the role of retinoic acid in regulating downstream transcription factors essential for spermatogenesis.
- To elucidate the effect of retinoids on the expression of cAMP responsive element modulator (CREM).
Main Methods:
- Utilized vitamin A deficiency (VAD) rat models.
- Administered all-trans retinoic acid (ATRA) or retinol to VAD rats.
- Analyzed testicular mRNA levels of CREM using RT-PCR.
Main Results:
- Administration of ATRA or retinol to VAD rats down-regulated testicular CREM mRNA levels.
- Dietary retinoid depletion led to up-regulated CREM expression in adult testes.
- ATRA specifically repressed the expression of the CREM activator spliced variant (CREMtau).
Conclusions:
- Retinoids act as negative regulators of CREM expression in the testes.
- This regulation is critical for maintaining proper spermatogenesis.
- Findings shed light on the molecular control of sperm development by vitamin A.
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