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Article: Dynamic regulation of sperm interactions with the zona pellucida prior to and after fertilisation.

Gadella, B M

Reproduction, fertility, and development

2012 Volume 25, Issue 1, Page(s) 26–37

Abstract: Recent findings have refined our thinking on sperm interactions with the cumulus-oocyte complex (COC) and our understanding of how, at the molecular level, the sperm cell fertilises the oocyte. Proteomic analyses has identified a capacitation-dependent ... ...

Abstract	Recent findings have refined our thinking on sperm interactions with the cumulus-oocyte complex (COC) and our understanding of how, at the molecular level, the sperm cell fertilises the oocyte. Proteomic analyses has identified a capacitation-dependent sperm surface reordering that leads to the formation of functional multiprotein complexes involved in zona-cumulus interactions in several mammalian species. During this process, multiple docking of the acrosomal membrane to the plasma membrane takes place. In contrast with the dogma that the acrosome reaction is initiated when spermatozoa bind to the zona pellucida (ZP), it has been established recently that, in mice, the fertilising spermatozoon initiates its acrosome reaction during its voyage through the cumulus before it reaches the ZP. In fact, even acrosome-reacted mouse spermatozoa collected from the perivitelline space can fertilise another ZP-intact oocyte. The oviduct appears to influence the extracellular matrix properties of the spermatozoa as well as the COC. This may influence sperm binding and penetration of the cumulus and ZP, and, in doing so, increase monospermic while decreasing polyspermic fertilisation rates. Structural analysis of the ZP has shed new light on how spermatozoa bind and penetrate this structure and how the cortical reaction blocks sperm-ZP interactions. The current understanding of sperm interactions with the cumulus and ZP layers surrounding the oocyte is reviewed with a special emphasis on the lack of comparative knowledge on this topic in humans, as well as in most farm mammals.
MeSH term(s)	Acrosome Reaction ; Animals ; Cumulus Cells/physiology ; Exocytosis ; Female ; Fertilization ; Fertilization in Vitro ; Humans ; Male ; Oocytes/physiology ; Oviducts/physiology ; Sperm Capacitation ; Sperm-Ovum Interactions ; Spermatozoa/enzymology ; Spermatozoa/physiology
Language	English
Publishing date	2012
Publishing country	Australia
Document type	Journal Article ; Review
ZDB-ID	1019913-5
ISSN	1448-5990 ; 1031-3613
ISSN (online)	1448-5990
ISSN	1031-3613
DOI	10.1071/RD12277
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Article: Interaction of sperm with the zona pellucida during fertilization.

Gadella, B M

Society of Reproduction and Fertility supplement

2011 Volume 67, Page(s) 267–287

Abstract: In order to achieve fertilization sperm cells, first need to successfully interact with the zona pellucida. To this end, the sperm surface is extensively remodeled during capacitation and the resulting sperm cells also possess hyperactivated motility. ... ...

Abstract	In order to achieve fertilization sperm cells, first need to successfully interact with the zona pellucida. To this end, the sperm surface is extensively remodeled during capacitation and the resulting sperm cells also possess hyperactivated motility. Together, this serves to mediate optimal recognition of the zona pellucida in the oviduct or after in vitro fertilization incubations (primary zona pellucida binding). When the sperm cell attaches to the zona pellucida, it will be triggered to undergo the acrosome reaction which allows the hyperactivated motile sperm cell to drill through the zona pellucida (secondary zona pellucida binding coinciding with sequential local zona pellucida digestion and rebinding). After successful zona penetration, some sperm cells may enter the perivitelline space. This delaying strategy of the oocyte allows only one sperm cell at a given time to bind and fuse with the oocyte (fertilization) and thus minimizes the risk of polyspermy. The fertilization fusion between the oocyte and the first sperm cell is immediately followed by a polyspermic fertilization block, in which the content of the oocyte's cortical granules is released into the perivitelline space. The cortical reaction blocks further sperm-oocyte fusion either by sticking at the oolemma or by the induction of a biochemical reaction of the zona pellucida (zona pellucida hardening). The cortical reaction thus blocks sperm-zona pellucida binding and/or sperm-zona pellucida penetration. This review summarizes the current understanding of sperm-zona pellucida interactions in relation to mammalian fertilization. The lack of knowledge about sperm-zona pellucida binding in ruminants will be critically discussed.
MeSH term(s)	Animals ; Female ; Male ; Sperm-Ovum Interactions/physiology ; Spermatozoa/physiology ; Zona Pellucida/physiology
Language	English
Publishing date	2011-07-08
Publishing country	England
Document type	Journal Article ; Review
ISSN	1747-3403
ISSN	1747-3403
DOI	10.7313/upo9781907284991.023
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Article ; Online: An update on post-ejaculatory remodeling of the sperm surface before mammalian fertilization.

Gadella, B M / Boerke, A

Theriogenology

2016 Volume 85, Issue 1, Page(s) 113–124

Abstract: The fusion of a sperm with an oocyte to form new life is a highly regulated event. The activation-also termed capacitation-of the sperm cell is one of the key preparative steps required for this process. Ejaculated sperm has to make a journey through the ...

Abstract	The fusion of a sperm with an oocyte to form new life is a highly regulated event. The activation-also termed capacitation-of the sperm cell is one of the key preparative steps required for this process. Ejaculated sperm has to make a journey through the female uterus and oviduct before it can approach the oocyte. The oocyte at that moment also has become prepared to facilitate monospermic fertilization and block immediately thereafter the chance for polyspermic fertilization. Interestingly, ejaculated sperm is not properly capacitated and consequently is not yet able to fertilize the oocyte. During the capacitation process, the formation of competent lipid-protein domains on the sperm head enables sperm-cumulus and zona pellucida interactions. This sperm binding allows the onset for a cascade reaction ultimately resulting in oocyte-sperm fusion. Many different lipids and proteins from the sperm surface are involved in this process. Sperm surface processing already starts when sperm are liberated from the seminiferous tubules and is followed by epididymal maturation where the sperm cell surface is modified and loaded with proteins to ensure it is prepared for its fertilization task. Although cauda epididymal sperm can fertilize the oocyte IVF, they are coated with so-called decapacitation factors during ejaculation. The seminal plasma-induced stabilization of the sperm surface permits the sperm transit through the cervix and uterus but prevents sperm capacitation and thus inhibits fertilization. For IVF purposes, sperm are washed out of seminal plasma and activated to get rid of decapacitation factors. Only after capacitation, the sperm can fertilize the oocyte. In recent years, IVF has become a widely used tool to achieve successful fertilization in both the veterinary field and human medicine. Although IVF procedures are very successful, scientific knowledge is still far from complete when identifying all the molecular players and processes during the first stages the fusion of two gametes into a new life. A concise overview in the current understanding of the process of capacitation and the sperm surface changes is provided. The gaps in knowledge of these prefertilization processes are critically discussed.
MeSH term(s)	Animals ; Ejaculation/physiology ; Female ; Fertilization/physiology ; Male ; Mammals/physiology ; Oocytes/physiology ; Spermatozoa/cytology ; Spermatozoa/physiology
Language	English
Publishing date	2016-01-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	189232-0
ISSN	1879-3231 ; 0093-691X
ISSN (online)	1879-3231
ISSN	0093-691X
DOI	10.1016/j.theriogenology.2015.07.018
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Article ; Online: Characterization of different oligomeric forms of CRISP2 in the perinuclear theca versus the fibrous tail structures of boar spermatozoa†.

Zhang, M / Bromfield, E G / Veenendaal, T / Klumperman, J / Helms, J B / Gadella, B M

Biology of reproduction

2021 Volume 105, Issue 5, Page(s) 1160–1170

Abstract: Mammalian sperm carry a variety of highly condensed insoluble protein structures such as the perinuclear theca, the fibrous sheath and the outer dense fibers, which are essential to sperm function. We studied the role of cysteine rich secretory protein 2 ...

Abstract	Mammalian sperm carry a variety of highly condensed insoluble protein structures such as the perinuclear theca, the fibrous sheath and the outer dense fibers, which are essential to sperm function. We studied the role of cysteine rich secretory protein 2 (CRISP2); a known inducer of non-pathological protein amyloids, in pig sperm with a variety of techniques. CRISP2, which is synthesized during spermatogenesis, was localized by confocal immunofluorescent imaging in the tail and in the post-acrosomal region of the sperm head. High-resolution localization by immunogold labeling electron microscopy of ultrathin cryosections revealed that CRISP2 was present in the perinuclear theca and neck region of the sperm head, as well as in the outer dense fibers and the fibrous sheath of the sperm tail. Interestingly, we found that under native, non-reducing conditions CRISP2 formed oligomers both in the tail and the head but with different molecular weights and different biochemical properties. The tail oligomers were insensitive to reducing conditions but nearly complete dissociated into monomers under 8 M urea treatment, while the head 250 kDa CRISP2 positive oligomer completely dissociated into CRISP2 monomers under reducing conditions. The head specific dissociation of CRISP2 oligomer is likely a result of the reduction of various sulfhydryl groups in the cysteine rich domain of this protein. The sperm head CRISP2 shared typical solubilization characteristics with other perinuclear theca proteins as was shown with sequential detergent and salt treatments. Thus, CRISP2 is likely to participate in the formation of functional protein complexes in both the sperm tail and sperm head, but with differing oligomeric organization and biochemical properties. Future studies will be devoted to the understand the role of CRISP2 in sperm protein complexes formation and how this contributes to the fertilization processes.
MeSH term(s)	Animals ; Cell Adhesion Molecules/genetics ; Cell Adhesion Molecules/metabolism ; Cytoskeleton/metabolism ; Male ; Sperm Tail/metabolism ; Spermatogenesis ; Spermatozoa/metabolism ; Sus scrofa/physiology
Chemical Substances	Cell Adhesion Molecules
Language	English
Publishing date	2021-07-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1118-6
ISSN	1529-7268 ; 0006-3363
ISSN (online)	1529-7268
ISSN	0006-3363
DOI	10.1093/biolre/ioab145
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Article: An update on post-ejaculatory remodeling of the sperm surface before mammalian fertilization

Gadella, B.M / A. Boerke

Theriogenology. 2016 Jan. 01, v. 85, no. 1

2016

Abstract: The fusion of a sperm with an oocyte to form new life is a highly regulated event. The activation—also termed capacitation—of the sperm cell is one of the key preparative steps required for this process. Ejaculated sperm has to make a journey through the ...

Abstract	The fusion of a sperm with an oocyte to form new life is a highly regulated event. The activation—also termed capacitation—of the sperm cell is one of the key preparative steps required for this process. Ejaculated sperm has to make a journey through the female uterus and oviduct before it can approach the oocyte. The oocyte at that moment also has become prepared to facilitate monospermic fertilization and block immediately thereafter the chance for polyspermic fertilization. Interestingly, ejaculated sperm is not properly capacitated and consequently is not yet able to fertilize the oocyte. During the capacitation process, the formation of competent lipid-protein domains on the sperm head enables sperm-cumulus and zona pellucida interactions. This sperm binding allows the onset for a cascade reaction ultimately resulting in oocyte-sperm fusion. Many different lipids and proteins from the sperm surface are involved in this process. Sperm surface processing already starts when sperm are liberated from the seminiferous tubules and is followed by epididymal maturation where the sperm cell surface is modified and loaded with proteins to ensure it is prepared for its fertilization task. Although cauda epididymal sperm can fertilize the oocyte IVF, they are coated with so-called decapacitation factors during ejaculation. The seminal plasma–induced stabilization of the sperm surface permits the sperm transit through the cervix and uterus but prevents sperm capacitation and thus inhibits fertilization. For IVF purposes, sperm are washed out of seminal plasma and activated to get rid of decapacitation factors. Only after capacitation, the sperm can fertilize the oocyte. In recent years, IVF has become a widely used tool to achieve successful fertilization in both the veterinary field and human medicine. Although IVF procedures are very successful, scientific knowledge is still far from complete when identifying all the molecular players and processes during the first stages the fusion of two gametes into a new life. A concise overview in the current understanding of the process of capacitation and the sperm surface changes is provided. The gaps in knowledge of these prefertilization processes are critically discussed.
Keywords	cervix ; ejaculation ; epididymis ; females ; in vitro fertilization ; lipids ; mammals ; medicine ; oocytes ; oviducts ; proteins ; seminal plasma ; seminiferous tubules ; sperm capacitation ; spermatozoa ; uterus ; zona pellucida
Language	English
Dates of publication	2016-0101
Size	p. 113-124.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	189232-0
ISSN	1879-3231 ; 0093-691X
ISSN (online)	1879-3231
ISSN	0093-691X
DOI	10.1016/j.theriogenology.2015.07.018
Database	NAL-Catalogue (AGRICOLA)

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Article: Fatty Acid Supplementation During

Aardema, H / Bertijn, I / van Tol, Hta / Rijneveld, A / Vernooij, Jcm / Gadella, B M / Vos, Plam

Frontiers in cell and developmental biology

2022 Volume 10, Page(s) 837405

Abstract: ... In ... ...

Abstract	In vitro
Language	English
Publishing date	2022-03-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2022.837405
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Article ; Online: Bovine

Asimaki, K / Vazakidou, P / van Tol, H T A / Oei, C H Y / Modder, E A / van Duursen, M B M / Gadella, B M

Frontiers in toxicology

2022 Volume 4, Page(s) 811285

Abstract: Endocrine disrupting chemicals (EDCs) can interfere with normal hormonal action and regulation. Exposure of women to EDCs has been associated with adverse reproductive health outcomes. The assays currently used to identify EDCs that elicit female ... ...

Abstract	Endocrine disrupting chemicals (EDCs) can interfere with normal hormonal action and regulation. Exposure of women to EDCs has been associated with adverse reproductive health outcomes. The assays currently used to identify EDCs that elicit female reproductive toxicity lack screening tests that address effects on the maturation of oocytes, a process that enables them to be fertilized and develop into embryos. Here, a screening method employing the bovine model of
Language	English
Publishing date	2022-05-24
Publishing country	Switzerland
Document type	Journal Article
ISSN	2673-3080
ISSN (online)	2673-3080
DOI	10.3389/ftox.2022.811285
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Article ; Online: A Review of New Technologies that may Become Useful for in vitro Production of Boar Sperm.

Gadella, B M / Ferraz, M A

Reproduction in domestic animals = Zuchthygiene

2015 Volume 50 Suppl 2, Page(s) 61–70

Abstract: Making sperm cells outside the original testicular environment in a culture dish has been considered for a long time as impossible due to the very complicated process of spermatogenesis and sperm maturation, which altogether, encompasses a 2-month period. ...

Abstract	Making sperm cells outside the original testicular environment in a culture dish has been considered for a long time as impossible due to the very complicated process of spermatogenesis and sperm maturation, which altogether, encompasses a 2-month period. However, new approaches in complex three-dimensional co-cell cultures, micro-perfusion and micro-fluidics technologies, new knowledge in the functioning, culturing and differentiation of spermatogonial stem cells (SSC) and their precursor cells have revolutionized this field. Furthermore, the use of better molecular markers as well as stimulatory factors has led to successful in vitro culture of stem cells either derived from germ line stem cells, from induced pluripotent stem cells (iPSC) or from embryonic stem cells (ESC). These stem cells when placed into small seminiferous tubule fragments are able to become SSC. The SSC beyond self-renewal can also be induced into haploid sperm-like cells under in vitro conditions. In mouse, this in vitro produced sperm can be injected into a mature oocyte and allow post-fertilization development into an early embryo in vitro. After transferring such obtained embryos into the uterus of a recipient mouse, they can further develop into healthy offspring. Recently, a similar approach has been performed with combining selected cells from testicular cell suspensions followed by a complete in vitro culture of seminiferous cords producing sperm-like cells. However, most of the techniques developed are laborious, time-consuming and have low efficiency, placing questionable that it will become useful used for setting up an efficient in vitro sperm production system for the boar. The benefits and drawbacks as well as the likeliness of in vitro pig sperm production to become applied in assisted technologies for swine reproduction are critically discussed. In this contribution, also the process of sperm production in the testis and sperm maturation is reviewed.
MeSH term(s)	Animals ; Cell Culture Techniques/methods ; Cell Culture Techniques/veterinary ; Cell Differentiation ; Coculture Techniques/methods ; Coculture Techniques/veterinary ; Embryonic Stem Cells ; Fertilization ; Male ; Reproductive Techniques, Assisted/veterinary ; Seminiferous Tubules ; Sperm Maturation ; Spermatids ; Spermatogenesis ; Spermatogonia/transplantation ; Spermatozoa/growth & development ; Stem Cells ; Swine ; Testis/cytology
Language	English
Publishing date	2015-07
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	1015187-4
ISSN	1439-0531 ; 0936-6768
ISSN (online)	1439-0531
ISSN	0936-6768
DOI	10.1111/rda.12571
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Article: Sperm membrane physiology and relevance for fertilization.

Gadella, B M

Animal reproduction science

2008 Volume 107, Issue 3-4, Page(s) 229–236

Abstract: This paper aims to overview recent insights in sperm surface remodelling pertinent to fertilization. A basic understanding of this remodelling is required to interpret the high amount of data appearing from high-throughput identification techniques for ... ...

Abstract	This paper aims to overview recent insights in sperm surface remodelling pertinent to fertilization. A basic understanding of this remodelling is required to interpret the high amount of data appearing from high-throughput identification techniques for proteins presently applied in reproductive biology. From the extensive lists of protein candidates identified by proteomics, only a few are recognized to be directly involved in fertilization. Others are indirectly involved, but many are not yet considered to be involved in fertilization. Some of these newly identified and unexpected proteins may shed new light in the current molecular models for fertilization. However, the gathered lists of sperm proteins possibly involved in fertilization do only tell a part of the story regarding how fertilization is accomplished. When considering the identification of proteins involved in fertilization, one also needs to take into account the fundamental mechanisms involved in the redistribution of sperm surface proteins in membrane protein complexes and the involvement of cell signalling events that regulate their post-translational modification status. Both processes are likely requisite for protein configuration and grouping into functional membrane protein complexes necessary to elicit their delicate roles in fertilization. This paper emphasizes biochemical models for membrane surface modelling and their potential involvement for remodelling the sperm surface in the above described processes.
MeSH term(s)	Acrosome Reaction/physiology ; Animals ; Cell Membrane/physiology ; Female ; Fertilization/physiology ; Male ; Models, Biological ; Sperm Capacitation/physiology ; Sperm-Ovum Interactions/physiology ; Spermatozoa/physiology ; Zona Pellucida/metabolism ; Zona Pellucida/physiology
Language	English
Publishing date	2008-09
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	429674-6
ISSN	1873-2232 ; 0378-4320
ISSN (online)	1873-2232
ISSN	0378-4320
DOI	10.1016/j.anireprosci.2008.05.006
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Article ; Online: The assembly of a zona pellucida binding protein complex in sperm.

Gadella, B M

Reproduction in domestic animals = Zuchthygiene

2008 Volume 43 Suppl 5, Page(s) 12–19

Abstract: The surface of the sperm cell, after its production in the testis is heterogeneous and subjected to continuous surface remodelling during its voyage through the male and female genital tracts to reach the oocyte. This remodelling will result in a ... ...

Abstract	The surface of the sperm cell, after its production in the testis is heterogeneous and subjected to continuous surface remodelling during its voyage through the male and female genital tracts to reach the oocyte. This remodelling will result in a competent sperm that is suitably equipped to bind to the zona pellucida and to follow the processes required for fertilization. During in vitro fertilization (IVF) studies, some aspects of these surface remodelling are mimicked and optimized to achieve good fertilization rates in the reproductive clinic. Although, the IVF experiments with sperm provided knowledge about how sperm motility activation is achieved and gave insights into the extensive sperm surface remodelling that is needed to acquire the high zona binding affinity, it is far from clear how relevant these processes are, for the competent sperm that actually fertilizes the oocyte under in vivo conditions. Moreover, sperm surface remodelling, especially by the female genital tract, is only poorly understood. The aim of this study was to combine the knowledge we have about the sperm surface from in vitro and biochemical approaches on one hand and, on the other hand, to attempt to overview the molecular mechanisms involved in sperm surface remodelling at different places within the male and female genital tract. The relevance for this to predict and identify the proteins involved in sperm zona binding in vivo is discussed.
MeSH term(s)	Acrosome Reaction/physiology ; Animals ; Cell Membrane/physiology ; Female ; Fertilization/physiology ; Fertilization in Vitro/veterinary ; Male ; Sperm Capacitation/physiology ; Sperm Motility/physiology ; Sperm Transport/physiology ; Sperm-Ovum Interactions/physiology ; Spermatozoa/physiology ; Zona Pellucida/metabolism ; Zona Pellucida/physiology
Language	English
Publishing date	2008-11
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	1015187-4
ISSN	1439-0531 ; 0936-6768
ISSN (online)	1439-0531
ISSN	0936-6768
DOI	10.1111/j.1439-0531.2008.01255.x
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