Mysteries and unsolved problems of mammalian fertilization and related topics

Yanagimachi, Ryuzo

doi:10.1093/biolre/ioac037

Cited by 36 publications

(33 citation statements)

References 372 publications

(350 reference statements)

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“…Actually, more slow spermatozoa were found in Sirt1 +/− males, probably due to a compromised sperm metabolism. Moreover, given that SIRT1 insufficiency has been related to improper intracellular Ca 2+ regulation (Yang et al, 2020) and that Ca 2+ is critical for hyperactivation development (Yanagimachi, 2022), it is possible that SIRT1 modulates hyperactivation controlling Ca 2+ signalling pathways. All these results were consistent with the decreased ability to fertilize in vivo of the Sirt1 +/− males.…”

Section: Discussionmentioning

confidence: 99%

Male SIRT1 insufficiency leads to sperm with decreased ability to hyperactivate and fertilize

Iniesta‐Cuerda

Havránková

Řimnáčová

et al. 2022

Reprod Domestic Animals

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Sperm physiology is mainly affected by the functions of testis and, during spermatogenesis, sperm are provided of proteins driving posterior motility (Björkgren & Sipilä, 2019). For example, NAD +dependent histone deacetylases (Sirtuins) need to be expressed in testes for proper sperm motility (Coussens et al., 2008). Moreover, spermatozoa are transcriptionally and translationally silent, therefore the ability to acquire fertilization competence, i.e. support capacitation and hyperactivation, depends on the proteins already synthesized during spermatogenesis. Interestingly, aging results in decreased sirtuin 1 (SIRT1) expression in testes (Grabowska et al., 2017) and defective basal sperm motility (prior to capacitation). However, whether this SIRT1 insufficiency affects posterior sperm ability to hyperactivate deserves to be studied. To test this possibility, we compared the dynamics of motility-based sperm subpopulations during capacitation and fertilization ability of Sirt1 +/− mutant males and wild-type (WT) siblings. Our study support that (I) SIRT1 contributes sperm to go through hyperactivation and (II) Sirt1 +/− mice as good model to identify molecular factors developing the age-related sub-/infertility. | ME THODS | AnimalsFourteen to 18-week-old males of germ-line Sirt1 +/− (n = 3) and their WT (Sirt1 +/+ ) siblings (n = 3) were used. Sirt1 +/− genotype is based on the excision of exons 5, 6 and 7 of Sirt1 allele. Animal procedures were done in accordance with the ActNo.246/1992 of the Animal Welfare Advisory Committee (Czech Republic).

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Section: Discussionmentioning

confidence: 99%

Male SIRT1 insufficiency leads to sperm with decreased ability to hyperactivate and fertilize

Iniesta‐Cuerda

Havránková

Řimnáčová

et al. 2022

Reprod Domestic Animals

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“…For example, Rpn7 and Prosα7 were unable to be detected in DWT ( Figure 6 A), although they were indeed expressed in DTT. As discussed above, proteasomes play a pivotal function during spermatogenesis and fertilization in many animals, including mammals [ 43 , 53 , 54 , 55 , 56 ]. These suggest that many subunits of proteasome were deubiquitinated due to Wolbachia infection, which will alter the functions of UPP and impair male fertility.…”

Section: Discussionmentioning

confidence: 99%

Comparative Ubiquitome Analysis Reveals Deubiquitinating Effects Induced by Wolbachia Infection in Drosophila melanogaster

Zong

Mao

Zhang

et al. 2022

IJMS

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The endosymbiotic Wolbachia bacteria frequently cause cytoplasmic incompatibility (CI) in their insect hosts, where Wolbachia-infected males cross with uninfected females, leading to no or fewer progenies, indicating a paternal modification by Wolbachia. Recent studies have identified a Wolbachia protein, CidB, containing a DUB (deubiquitylating enzyme) domain, which can be loaded into host sperm nuclei and involved in CI, though the DUB activity is not necessary for CI in Drosophila melanogaster. To investigate whether and how Wolbachia affect protein ubiquitination in testes of male hosts and are thus involved in male fertility, we compared the protein and ubiquitinated protein expressions in D. melanogaster testes with and without Wolbachia. A total of 643 differentially expressed proteins (DEPs) and 309 differentially expressed ubiquitinated proteins (DEUPs) were identified to have at least a 1.5-fold change with a p-value of <0.05. Many DEPs were enriched in metabolic pathway, ribosome, RNA transport, and post-translational protein modification pathways. Many DEUPs were involved in metabolism, ribosome, and proteasome pathways. Notably, 98.1% DEUPs were downregulated in the presence of Wolbachia. Four genes coding for DEUPs in ubiquitin proteasome pathways were knocked down, respectively, in Wolbachia-free fly testes. Among them, Rpn6 and Rpn7 knockdown caused male sterility, with no mature sperm in seminal vesicles. These results reveal deubiquitylating effects induced by Wolbachia infection, suggesting that Wolbachia can widely deubiquitinate proteins that have crucial functions in male fertility of their hosts, but are not involved in CI. Our data provide new insights into the regulatory mechanisms of endosymbiont/host interactions and male fertility.

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“…Furthermore, it is known that head morphology may play a significant role in shaping the flagellar waveform. As such, there may be significant cross-species interest in understanding how whether this control mechanism is able to recreate what is seen across a wide-range of wildlife, including other mammalian species, fish and birds [49, 50].…”

Section: Discussionmentioning

confidence: 99%

Axonemal regulation by curvature explains sperm flagellar waveform modulation

Gallagher

Kirkman-Brown

Smith

2022

Preprint

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Flagellar motility is critical to natural and many forms of assisted reproduction. The rhythmic beating and wave propagation by the flagellum propels sperm through fluid and enables modulation between penetrative progressive motion, activated side-to-side yaw and hyperactivated movement associated with detachment from epithelial binding. These changes occur in response to the properties of the surrounding fluid environment, biochemical activation state, and physiological ligands, however a parsimonious mechanistic explanation of flagellar beat generation that can explain motility modulation is lacking. In this paper we present the Axonemal Regulation of Curvature, Hysteretic model (ARCH), a curvature control-type model based on switching of active moment by local curvature, embedded within a geometrically nonlinear elastic model of the flagellum exhibiting planar flagellar beats, together with nonlocal viscous fluid dynamics. The biophysical system is parameterised completely by four dimensionless parameter groupings. The effect of parameter variation is explored through computational simulation, revealing beat patterns that are qualitatively representative of penetrative (straight progressive), activated (highly yawing) and hyperactivated (non-progressive) modes. Analysis of the flagellar limit cycles and associated swimming velocity reveals a cusp catastrophe between progressive and non-progressive modes, and hysteresis in the response to changes in critical curvature parameter. Quantitative comparison to experimental data on human sperm exhibiting typical penetrative, activated and hyperactivated beats shows a good fit to the time-average absolute curvature profile along the flagellum, providing evidence that the model is capable of providing a framework for quantitative interpretation of imaging data.

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Mysteries and unsolved problems of mammalian fertilization and related topics

Cited by 36 publications

References 372 publications

Male SIRT1 insufficiency leads to sperm with decreased ability to hyperactivate and fertilize

Male SIRT1 insufficiency leads to sperm with decreased ability to hyperactivate and fertilize

Comparative Ubiquitome Analysis Reveals Deubiquitinating Effects Induced by Wolbachia Infection in Drosophila melanogaster

Axonemal regulation by curvature explains sperm flagellar waveform modulation

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