ArticleJournal of andrology
Suppression of spermatogenesis by bisdichloroacetyldiamines is mediated by inhibition of testicular retinoic acid biosynthesis.
Article in Journal of andrology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
90 citing papers in PubMed, 132 citations in OpenAlex.
- Isotretinoin administration improves sperm production in men with infertility from oligoasthenozoospermia: a pilot study.Andrology · 2017Trial
- Novel male contraceptives.Future science OA · 2026Review
- Why male contraception still stalls: translational, social, and ethical gaps.Annals of medicine and surgery (2012) · 2026Article
- Article
- Identification and characterization of a novel aldehyde metabolite of WIN18,446 and associated WIN18,446-ALDH1A2 protein adducts using mass spectrometry.Drug metabolism reviews · 2026Article
- Reviewing the Implication of Aldehyde Dehydrogenases in Male Reproduction: Prospects for New Therapeutic Approaches.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Development of retinoid nuclear receptor pathway antagonists through targeting aldehyde dehydrogenase 1A3.iScience · 2025Article
- Kinetics of the inhibition and recovery of spermatogenesis induced by treatment with WIN 18,446, a male contraceptive, in mice.Andrology · 2025Article
- Safety and pharmacokinetics of the non-hormonal male contraceptive YCT-529.Communications medicine · 2025Article
- The effect of induced molting on the testicular physiological remodeling in no-semen roosters.BMC genomics · 2025Article
- Non-hormonal Contraception: Current and Emerging Targets.Advances in experimental medicine and biology · 2025Review
- Emerging approaches to male contraception.Andrology · 2024Review
- The pathogenic role of retinoid nuclear receptor signaling in cancer and metabolic syndromes.The Journal of experimental medicine · 2024Review
- Review
- Reversible Contraception in Males: An Obtainable Target?Biology · 2024Review
- Restoration of fertility in nonablated recipient mice after spermatogonial stem cell transplantation.Stem cell reports · 2024Article
- PRC1 directs PRC2-H3K27me3 deposition to shield adult spermatogonial stem cells from differentiation.Nucleic acids research · 2024Article
- Targeting nuclear receptor corepressors for reversible male contraception.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Return to fertility, toxicology, and transgenerational impact of treatment with WIN 18,446, a potential male contraceptive, in mice.Contraception · 2024Article
- Induction of Meiotic Initiation in Long-Term Mouse Spermatogonial Stem Cells Under Retinoid Acid and Nutrient Restriction Conditions.Methods in molecular biology (Clifton, N.J.) · 2024Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The bisdichloroacetyldiamine WIN 18,446 reversibly inhibits spermatogenesis in many species, including humans; however, the mechanism by which WIN 18,446 functions is unknown. As retinoic acid is essential for spermatogenesis, we hypothesized that WIN 18,446 might inhibit retinoic acid biosynthesis from retinol (vitamin A) within the testes by inhibiting the enzyme aldehyde dehydrogenase 1a2 (ALDH1a2). We studied the effect of WIN 18,446 on ALDH1a2 enzyme activity in vitro, and on spermatogenesis and fertility in vivo, in mature male rabbits for 16 weeks. WIN 18,446 markedly inhibited ALDH1a2 enzyme activity in vitro with an IC(50) of 0.3 μM. In vivo, the oral administration of 200 mg/kg WIN 18,446 to male rabbits for 16 weeks significantly reduced intratesticular concentrations of retinoic acid, severely impaired spermatogenesis, and caused infertility. Reduced concentrations of intratesticular retinoic acid were apparent after only 4 weeks of treatment and preceded the decrease in sperm counts and the loss of mature germ cells in tissue samples. Sperm counts and fertility recovered after treatment was discontinued. These findings demonstrate that bisdichloroacetyldiamines such as WIN 18,446 reversibly suppress spermatogenesis via inhibition of testicular retinoic acid biosynthesis by ALDH1a2. These findings suggest that ALDH1a2 is a promising target for the development of a reversible, nonhormonal male contraceptive.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.