Evidence map›Paper›PMID 42212558›Full record

ArticleHuman reproduction (Oxford, England)2026

ABHD2 activity is not required for the non-genomic action of progesterone on human sperm.

Madison Edwards, Alexandra Amaral, Eve M Carter, Oliver Arnolds, Karen Vester, Anna Thrun, Edvard Wigren, Evert Homan, Pauline Ribera, Kirsty Bentley and 20 more

Abstract read
In one paragraph

Article in Human reproduction (Oxford, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

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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.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

30 authors.

Madison EdwardsStructural Genomics Consortium (SGC), University of Toronto, Toronto, Canada.
Alexandra AmaralNuvisan ICB GMBH, Berlin, Germany.
Eve M CarterSchool of Pharmacy and Structural Genomics Consortium, University College London, London, UK.
Oliver ArnoldsStructural Genomics Consortium (SGC) and Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Karen VesterNuvisan ICB GMBH, Berlin, Germany.
Anna ThrunNuvisan ICB GMBH, Berlin, Germany.
Edvard WigrenStructural Genomics Consortium (SGC) and Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-7933-0939
Evert HomanDepartment of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Pauline RiberaChemical Biology Consortium Sweden (CBCS), Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Kirsty BentleyDepartment of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Martin HaraldssonChemical Biology Consortium Sweden (CBCS), Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Nmesoma Theo-EmeganoStructural Genomics Consortium (SGC), University of Toronto, Toronto, Canada.
Peter LoppnauStructural Genomics Consortium (SGC), University of Toronto, Toronto, Canada.
Magdalena M SzewczykStructural Genomics Consortium (SGC), University of Toronto, Toronto, Canada.
Michelle A CaoStructural Genomics Consortium (SGC), University of Toronto, Toronto, Canada.
Dalia Barsyte-LovejoyStructural Genomics Consortium (SGC), University of Toronto, Toronto, Canada.ORCID 0000-0002-6560-9621
Nicole DittmarNuvisan ICB GMBH, Berlin, Germany.
Anika HansNuvisan ICB GMBH, Berlin, Germany.
Mandy WeberNuvisan ICB GMBH, Berlin, Germany.
Jens MünchowInstitute of Pharmaceutical and Medicinal Chemistry, University of Münster, Münster, Germany.
W Felix ZhuInstitute of Pharmaceutical and Medicinal Chemistry, University of Münster, Münster, Germany.
Louisa TemmeGRK 2515, Chemical Biology of Ion Channels (Chembion), University of Münster, Münster, Germany.
Christoph BrenkerCenter of Reproductive Medicine and Andrology, University of Münster, University Hospital Münster, Münster, Germany.ORCID 0000-0002-4230-2571
Timo StrünkerGRK 2515, Chemical Biology of Ion Channels (Chembion), University of Münster, Münster, Germany.ORCID 0000-0003-0812-1547
Michael SundströmStructural Genomics Consortium (SGC) and Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Matthew H ToddSchool of Pharmacy and Structural Genomics Consortium, University College London, London, UK.
Aled M EdwardsStructural Genomics Consortium (SGC), University of Toronto, Toronto, Canada.
Ralf LescheNuvisan ICB GMBH, Berlin, Germany.
Opher GileadiStructural Genomics Consortium (SGC) and Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-6886-898X
Claudia TredupInstitute of Pharmaceutical Chemistry, Goethe University Frankfurt, Frankfurt, Germany.ORCID 0000-0001-6518-3344

Funding

Contraception Research 01GR2501AContraception Research 01GR2502ADeutsche Forschungsgemeinschaft (DFG, German Research Foundation) 329621271Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) 404595355Gates FoundationGates Foundation INV-040467Gates Foundation INV-072213German Federal Ministry of Education and Research (BMBF)
6 · The paper itself

Abstract

study questionIs the hydrolase ABHD2 required for progesterone-induced Ca2+ influx via CatSper and the resulting motility responses in human sperm? SUMMARY ANSWER: Progesterone-induced Ca2+ influx via CatSper and the resulting motility responses in human sperm do not require ABHD2 activity. WHAT IS KNOWN ALREADY: Sperm motility is tightly regulated by signalling pathways that are activated as sperm ascend the female reproductive tract, including progesterone triggering Ca2+ influx via the CatSper channel and inducing hyperactivated motility needed for fertilization. This process is thought to involve ABHD2, which may hydrolyze the endogenous CatSper inhibitor 2-arachidonoylglycerol (2-AG), thereby relieving inhibition and enabling calcium entry into the flagellum. STUDY DESIGN, SIZE, DURATION: Potent small molecule inhibitors of ABHD2 activity were synthesized, characterized, and used as tools to scrutinize the role of ABHD2 in activation of CatSper and regulation of sperm motility. PARTICIPANTS/MATERIALS, SETTING,

methodsDerivatives of published ABHD2 inhibitors were optimized for in vitro potency and cellular activity and subsequently tested in human sperm motility and Ca2+ influx assays. MAIN RESULTS AND THE ROLE OF CHANCE: Progesterone does not activate ABHD2 in vitro. In addition, inhibition of ABHD2 in human sperm has no effect on progesterone-induced Ca2+ influx through CatSper nor on basal or progesterone-induced hyperactivated motility. This demonstrates that ABHD2 activity is, in fact, not required for the non-genomic action of progesterone on human sperm. LARGE SCALE DATA: None. LIMITATIONS, REASONS FOR CAUTION: We examined the effects of inhibition of the enzymatic activity of ABHD2. We cannot exclude that ABHD2 functions as a part of a larger multiprotein complex, in which it may play a structural role independent of its hydrolase activity. WIDER IMPLICATIONS OF THE

findingsThis study presents conclusive evidence that ABHD2 does not bind progesterone and that its hydrolase activity is not required for progesterone activation of CatSper and resulting changes in motility of human sperm. These results highlight the need for further research to elucidate the mechanism underlying the non-genomic action of progesterone on human sperm. STUDY FUNDING/COMPETING INTEREST(S): This publication is based on research funded by the Gates Foundation, reference IDs INV-040467 and ID INV-072213. The findings and conclusions contained within are those of the authors and do not necessarily reflect the positions or policies of the Gates Foundation. LT, CB, and TS were supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)-project numbers 329621271 (CRU326; CB, TS), and 404595355 (Research Training Group 'Chemical biology of ion channels (Chembion)'; LT, TS). This work was funded by the German Federal Ministry of Education and Research (BMBF) within the framework of Contraception Research, grant numbers 01GR2501A and 01GR2502A. A.A., K.V., A.T., N.D., A.H., M.W., and R.L. are employees of Nuvisan ICB GMBH, Berlin, Germany. Nuvisan is a recipient of a Gates Foundation grant. A.A. is associate editor of Human Reproduction Open.

Indexed as

Monoacylglycerol LipasesProgesteroneSpermatozoaSperm MotilityCalciumCalcium ChannelsCalcium SignalingHumansHydrolasesMaleSperm ProteinsABHD2 protein, humanCalciumCalcium ChannelsCATSPER1 protein, humanHydrolasesMonoacylglycerol LipasesProgesteroneSperm ProteinsABHD2CatSperhuman spermhyperactivationprogesterone receptor

Identifiers

PMID42212558
PMCPMC13429874

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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.