Retinoic Acid Signaling in Spermatogenesis: Spatial and Temporal Checkpoints, Male Infertility, and Contraceptive Development
- 1Hubei Key Laboratory of Embryonic Stem Cell Research, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan 442000, China
- 2Biomedical Engineering College, Hubei University of Medicine, Shiyan 442000, China
Abstract
Retinoic acid (RA), a bioactive vitamin A metabolite, is required at specific stages of mammalian spermatogenesis. This narrative review examines experimental evidence for these stage-specific functions and their relevance to infertility treatment and male contraception. We organize primary evidence around local ligand supply, exposure timing, cellular response, and developmental checkpoints, distinguishing causal findings in defined models from human associations and translational hypotheses. Genetic and pharmacological studies establish a requirement for RA in spermatogonial differentiation, whereas its requirements during subsequent meiosis and spermiogenesis depend on the experimental window and endpoint. The review also examines nutrition, thyroid status, environmental exposures, and DNA-damage responses. Human tissue studies describe variation in retinoid metabolism, but a clinical diagnosis of RA deficiency remains unvalidated. Small uncontrolled isotretinoin studies report semen changes and sperm-retrieval outcomes, but co-interventions and heterogeneous diagnoses limit causal attribution; spontaneous pregnancy, assisted reproduction, and live birth remain distinct outcomes. RA-synthesis inhibitors and selective receptor antagonists have stronger animal evidence for fertility suppression and recovery. Human contraceptive evidence remains limited to early clinical pharmacology. Translation requires controlled efficacy studies, appropriate measures of testicular exposure or response, and separate evaluation of sperm output, fertility, recovery, and safety.
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BibTeX
@article{liu2026retinoic,
title = {{Retinoic Acid Signaling in Spermatogenesis: Spatial and Temporal Checkpoints, Male Infertility, and Contraceptive Development}},
author = {Bowen Liu and Wending Wang and Chenchen Ye and Haixia Yu and Yidan Fan and Yutao Cai and Haili Wang and Ling Liu and Yan Tan},
journal = {Biomolecules},
year = {2026},
month = nov,
doi = {10.3390/biom16111582},
url = {https://www.mdpi.com/2218-273X/16/11/1582},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Retinoic Acid Signaling in Spermatogenesis: Spatial and Temporal Checkpoints, Male Infertility, and Contraceptive Development
AU - Bowen Liu
AU - Wending Wang
AU - Chenchen Ye
AU - Haixia Yu
AU - Yidan Fan
AU - Yutao Cai
AU - Haili Wang
AU - Ling Liu
AU - Yan Tan
PY - 2026
DA - 2026/11/01
JO - Biomolecules
DO - 10.3390/biom16111582
UR - https://www.mdpi.com/2218-273X/16/11/1582
AB - Retinoic acid (RA), a bioactive vitamin A metabolite, is required at specific stages of mammalian spermatogenesis. This narrative review examines experimental evidence for these stage-specific functions and their relevance to infertility treatment and male contraception. We organize primary evidence around local ligand supply, exposure timing, cellular response, and developmental checkpoints, distinguishing causal findings in defined models from human associations and translational hypotheses. Genetic and pharmacological studies establish a requirement for RA in spermatogonial differentiation, whereas its requirements during subsequent meiosis and spermiogenesis depend on the experimental window and endpoint. The review also examines nutrition, thyroid status, environmental exposures, and DNA-damage responses. Human tissue studies describe variation in retinoid metabolism, but a clinical diagnosis of RA deficiency remains unvalidated. Small uncontrolled isotretinoin studies report semen changes and sperm-retrieval outcomes, but co-interventions and heterogeneous diagnoses limit causal attribution; spontaneous pregnancy, assisted reproduction, and live birth remain distinct outcomes. RA-synthesis inhibitors and selective receptor antagonists have stronger animal evidence for fertility suppression and recovery. Human contraceptive evidence remains limited to early clinical pharmacology. Translation requires controlled efficacy studies, appropriate measures of testicular exposure or response, and separate evaluation of sperm output, fertility, recovery, and safety.
SN - 2218-273X
ER -