The thiol reagent, thimerosal, irreversibly inhibits meiosis reinitiation in mouse oocyte when applied during a very early and narrow temporal window: A pharmacological analysis

Alexandre, Henri; Delsinne, Virginie; Goval, J-J

doi:10.1002/mrd.10319

Cited by 7 publications

(7 citation statements)

References 84 publications

(88 reference statements)

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“…We show here that complete interphasic microtubule network disorganisation is a very early consequence of a pulse with TMS that was shown to irreversibly inhibit mouse oocyte maturation as a consequence of its thiol oxidising activity (Alexandre et al, 2003). To the best of our knowledge, this is the first demonstration of an immediate, complete and long-lasting microtubule interphasic network disassembly induced by this thiol reagent which is in agreement with the well documented in vitro microtubule depolymerising activity and to its inhibitory activity on tubulin assembly (Brunner et al, 1991).…”

Section: Discussionmentioning

confidence: 83%

“…They also disarrange the cortical actin cytoskeleton but much more slightly than they do with microtubules (Milzani et al, 1997). This obviously explain why membrane ruffling is only reduced instead of being suppressed (Alexandre et al, 2003).…”

Section: Discussionmentioning

confidence: 98%

“…Thimerosal (TMS, Sigma) and Thiosalicylic Acid (TSA, Sigma) were dissolved in the medium at the time of the experiment. Oocytes were usually pulsed with 0.4 mM TMS for 10 min and subsequently incubated for 19 hours in control medium or medium containing either10 µM taxol or 1 µM OA (Alexandre et al, 2003). The concentrations of other drugs in experimental media were: 200 µM IBMX and 0.4 mM TSA.…”

Section: Oocyte Collection Culture and Treatmentmentioning

confidence: 99%

“…The sulfhydryl reagent thimerosal (TMS) was demonstrated to trigger meiosis reinitiation in clam oocytes by eliciting an intracellular Ca 2+ surge (Lippai et al, 1995). In sharp contrast to this situation, we recently showed that TMS irreversibly inhibits in vitro spontaneous maturation of denuded primary mouse oocytes even when applied for a short period of time (10 min) immediately after their release from the follicles (Alexandre et al, 2003). This inhibition is bypassed by dithiothreitol (DTT), while thiosalicylic acid (TSA), an analog of TMS, exerts no effect on both germinal vesicle breakdown (GVBD) and the first polar body extrusion.…”

Section: Introductionmentioning

confidence: 99%

“…This inhibition is bypassed by dithiothreitol (DTT), while thiosalicylic acid (TSA), an analog of TMS, exerts no effect on both germinal vesicle breakdown (GVBD) and the first polar body extrusion. In addition, okadaic acid (OA), a potent inhibitor of protein phosphatases type 1 (PP1) and type 2 (PP2A), known to bypass the inhibitory effect on oocyte maturation of drugs interfering with protein kinases activities (Rime and Ozon, 1990;Alexandre et al, 1991;Gavin et al, 1991;Van Cauwenberge and Alexandre, 2000), induces chromatin condensation and GVBD in TMS-pulsed oocytes with a delay of about 8 hours as compared to the control situation (Alexandre et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Effect of taxol and okadaic acid on microtubule dynamics in thimerosal‐arrested primary mouse oocytes: a confocal study

Alexandre

Delsinne

Goval

et al. 2003

Biology of the Cell

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A pulse of thimerosal (TMS), a sulfhydryl reagent, induces an instantaneous, complete and long-lasting microtubule interphasic network disassembly in mouse primary oocytes, correlated with the irreversible inhibition of meiosis reinitiation This inhibition is bypassed by dithiothreitol (DTT) while thiosalicylic acid, an analog of TMS, does induce neither microtubules depolymerisation nor inhibition of reinitiation and resumption of meiosis. This strongly suggests that the dramatic and pleiotropic inhibitory effect of TMS is specifically related to its sulfhydryl group oxidising activity of critical molecules among which tubulin. In contrast to DTT, okadaic acid (OA), known to bypass the inhibitory effect of drugs interfering with protein kinase activities, induces a late chromatin condensation and GVBD in TMS-pulsed oocytes as compared to the control situation, with no significant concomitant microtubule assembly. These cytological features are suggested to be indirectly induced by a late MAPK activation and confirm that a very early thiol oxidation induced by TMS exerts a much more dramatic effect on resumption of meiosis than any pharmacological manipulation of protein kinase activities leading to activation of MPF. Finally, taxol was shown to promote tubulin polymerisation even when microtubules were irreversibly disassembled by thiol oxidation but fails to restore the ability to undergo maturation.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 98%

Section: Oocyte Collection Culture and Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of taxol and okadaic acid on microtubule dynamics in thimerosal‐arrested primary mouse oocytes: a confocal study

Alexandre

Delsinne

Goval

et al. 2003

Biology of the Cell

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Chemical activation of mammalian oocytes and its application in camelid reproductive biotechnologies: A review

Bellido-Quispe,

Arcce,

Pinzón-Osorio

et al. 2024

Animal Reproduction Science

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Oocyte activation deficiency and assisted oocyte activation: mechanisms, obstacles and prospects for clinical application

Kashir

Ganesh

Jones

et al. 2022

Human Reproduction Open

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Background Oocyte activation deficiency (OAD) is attributed to the majority of cases underlying failure of intracytoplasmic sperm injection (ICSI) cycles, the standard treatment for male factor infertility. Oocyte activation encompasses a series of concerted events, triggered by sperm-specific phospholipase C zeta (PLCζ), which elicits increases in free cytoplasmic calcium (Ca2+) in spatially and temporally specific oscillations. Defects in this specific pattern of Ca2+ release is directly attributable to most cases of OAD. Ca2+ release can be clinically mediated via assisted oocyte activation (AOA), a combination of mechanical, electrical and/or chemical stimuli which artificially promote an increase in the levels of intracytoplasmic Ca2+. However, concerns regarding safety and efficacy underlie potential risks that must be addressed before such methods can be safely widely used. Objective and Rationale Recent advances in current AOA techniques warrant a review of the safety and efficacy of these practices, to determine the extent to which AOA may be implemented in the clinic. Importantly, the primary challenges to obtaining data on the safety and efficacy of AOA must be determined. Such questions require urgent attention before widespread clinical utilisation of such protocols can be advocated. Search Methods A literature review was performed using databases including PubMed, Web of Science, Medline etc. using assisted oocyte activation, oocyte activation deficiency, calcium ionophores, intra-cytoplasmic sperm injection, phospholipase c zeta, oocyte activation, failed fertilisation, and fertilisation failure as keywords. Relevant articles published until June 2019 were analysed and included in the review, with an emphasis on studies assessing large scale efficacy and safety. Outcomes Contradictory studies on the safety and efficacy of AOA do not yet allow for the establishment of AOA as standard practice in the clinic. Heterogeneity in study methodology, inconsistent sample inclusion criteria, non-standardised outcome assessments, restricted sample size and animal model limitations render AOA strictly experimental. The main scientific concern impeding AOA utilisation in the clinic is the non-physiological method of Ca2+ release mediated by most AOA agents, coupled with a lack of holistic understanding regarding the physiological mechanism(s) underlying Ca2+ release at oocyte activation. Limitations, reasons for caution The number of studies with clinical relevance using AOA remains significantly low. A much wider range of studies examining outcomes using multiple AOA agents are required. Wider Implications In addition to addressing the five main challenges of studies assessing AOA safety and efficacy, more standardized, large-scale, multi-centre studies of AOA, as well as long term follow-up studies of children born from AOA, would provide evidence for establishing AOA as a treatment for infertility. The delivery of an activating agent that can more accurately recapitulate physiological fertilisation, such as recombinant PLCζ, is a promising prospect for the future of AOA. Further to PLCζ, many other avenues of physiological oocyte activation also require urgent investigation to assess other potential physiological avenues of AOA. Study Funding/Competing Interests DG was supported by Stanford University’s Bing Overseas Study Program. JK was supported by a Healthcare Research Fellowship Award (HF-14-16) made by Health and Care Research Wales (HCRW), alongside a National Science, Technology, and Innovation plan (NSTIP) project grant (15-MED4186-20) awarded by the King Abdulaziz City for Science and Technology (KACST). The authors have no competing interests to declare. Lay Summary At fertilisation, oocyte activation is triggered by sperm-specific phospholipase C zeta (PLCζ) by releasing calcium in specific patterns within the oocyte. A deficiency in this process underlies most cases of fertilisation failure in mammals. This process of calcium release can be clinically mimicked via assisted oocyte activation (AOA), involving a combination of mechanical, electrical and/or chemical stimuli. Recent advances in AOA techniques warrant a review of the safety and efficacy of these practices and of how AOA may be clinically implemented in the clinic. Herein, following a detailed literature review examining studies assessing large scale efficacy and safety, the main concern impeding clinical AOA implementation is its non-physiological nature, coupled with a lack of holistic understanding of physiological mechanism(s) underlying calcium release at fertilisation. We find that numerous questions require urgent attention before widespread clinical utilisation of such protocols can be advocated. We hope that this article will be able to aid the burgeoning number of researchers investigating the clinical efficacy of such methodology in further refining the practice until large scale utilisation can be achieved and accepted.

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The thiol reagent, thimerosal, irreversibly inhibits meiosis reinitiation in mouse oocyte when applied during a very early and narrow temporal window: A pharmacological analysis

Cited by 7 publications

References 84 publications

Effect of taxol and okadaic acid on microtubule dynamics in thimerosal‐arrested primary mouse oocytes: a confocal study

Effect of taxol and okadaic acid on microtubule dynamics in thimerosal‐arrested primary mouse oocytes: a confocal study

Chemical activation of mammalian oocytes and its application in camelid reproductive biotechnologies: A review

Oocyte activation deficiency and assisted oocyte activation: mechanisms, obstacles and prospects for clinical application

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