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Nicholas L. Cross

Bio: Nicholas L. Cross is an academic researcher from Oklahoma State University–Stillwater. The author has contributed to research in topics: Sperm & Acrosome reaction. The author has an hindex of 13, co-authored 13 publications receiving 1174 citations.

Papers
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Journal ArticleDOI
TL;DR: Lipid rafts of heterogeneous composition were identified in human sperm and the two raft components, GM1 and CD59, showed a partial sterol loss-dependent shift to the nonraft domain during capacitation.
Abstract: Ejaculated mammalian sperm must complete a final maturation, termed capacitation, before they can undergo acrosomal exocytosis and fertilize an egg. In human sperm, loss of sperm sterol is an obligatory, early event in capacitation. How sterol loss leads to acrosomal responsiveness is unknown. These experiments tested the hypothesis that loss of sperm sterol affects the organization of cold detergent-resistant membrane microdomains (lipid "rafts"). The GPI-linked protein CD59, the ganglioside GM1, and the protein flotillin-2 were used as markers for lipid rafts. In uncapacitated sperm, 51% of the CD59, 41% of the GM1, and 90% of the flotillin-2 were found in the raft fraction. During capacitation, sperm lost 67% of their 3beta-hydroxysterols, and the percentages of CD59 and GM1 in the raft fraction decreased to 34% and 31%, respectively. The distribution of flotillin-2 did not change. Preventing a net loss of sperm sterol prevented the loss of CD59 and GM1 from the raft fraction. Fluorescence microscopy showed CD59 and GM1 to be distributed over the entire sperm surface. Flotillin-2 was located mainly in the posterior head and midpiece. Patching using bivalent antibodies indicated that little of the GM1 and CD59 was stably associated in the same membrane rafts. Likewise, GM1 and flotillin-2 were not associated in the same membrane rafts. In summary, lipid rafts of heterogeneous composition were identified in human sperm and the two raft components, GM1 and CD59, showed a partial sterol loss-dependent shift to the nonraft domain during capacitation.

148 citations

Journal ArticleDOI
TL;DR: The inhibitory activity of unfractionated seminal plasma was significantly less, relative to the cholesterol content, than the activity of pure cholesterol, which is consistent with the idea that there are components in seminal plasma that partially counter the effect of cholesterol by promoting the development of acrosomal responsiveness.
Abstract: Seminal plasma inhibits human sperm from developing the ability to undergo the acrosome reaction. The inhibitory activity was identified as that of cholesterol on the basis of its solubility in organic solvents, its chromatographic behavior (adsorption, thin-layer, and gas chromatography), and its mass spectrum. Contrary to findings in other reports, no evidence for inhibitory proteins or peptides was found, and spermine was not an effective inhibitor. The inhibitory activity of untreated seminal plasma from individual ejaculates was highly correlated with the cholesterol content of the ejaculates (r = 0.96), suggesting that the amount of cholesterol determines the inhibitory activity of unfractionated seminal plasma. The inhibitory activity of unfractionated seminal plasma was significantly less, relative to the cholesterol content, than the activity of pure cholesterol, which is consistent with the idea that there are components in seminal plasma that partially counter the effect of cholesterol by promoting the development of acrosomal responsiveness.

116 citations

Journal ArticleDOI
TL;DR: Depending on how it is applied, seminal plasma can prevent or reverse the development of acrosomal responsiveness, and it can enhance or induce the acrosome reaction.
Abstract: Mammalian sperm do not respond to inducers of the acrosome reaction immediately after ejaculation They become responsive after they are removed from seminal plasma and incubated in an appropriate medium We tested the effects of seminal plasma on the development of acrosomal responsiveness Washed human sperm incubated 24 hr in vitro with 10% (v/v) seminal plasma did not complete an acrosome reaction when exposed to human follicular fluid, progesterone, or ionomycin Seminal plasma did not reduce sperm viability or motility Electron microscopy of sperm incubated 24 hr with 5% seminal plasma and then treated with progesterone revealed no sign of membrane fusion or other changes that are associated with the acrosome reaction During a 12-hr incubation, seminal plasma was 50% effective at inhibiting the acrosomal response to progesterone when diluted 821 ± 112 foid (mean ±SD, n = 3) Sperm that were incubated with seminal plasma for 24 hr and then washed free of the seminal plasma became acrosomally responsive over the following 24 hr, at a rate similar to that of sperm not incubated with seminal plasma in vitro When sperm were incubated 6 hr without seminal plasma and then seminal plasma was added, the sperm population transiently became more responsive to progesterone, and then became unresponsive During incubation in vitro, the ability of sperm to have an augmented response to a mixture of seminal plasma plus progesterone developed slightly earlier and more rapidly than ability to respond to progesterone alone When sperm were incubated 24 hr without seminal plasma, a few acrosome reacted in response to the addition of seminal plasma alone Therefore, depending on how it is applied, seminal plasma can prevent or reverse the development of acrosomal responsiveness, and it can enhance or induce the acrosome reaction © 1993 Wiley-Liss, Inc

79 citations

Journal ArticleDOI
TL;DR: The results support a model in which sperm unesterified cholesterol, or a molecule in equilibrium with it, suppresses acrosomal responsiveness, and cholesterol's effect may be, at least in part, at a point in the signal transduction pathway subsequent to the rise in intracellular‐free calcium.
Abstract: Human sperm become responsive to inducers of the acrosome reaction when they are washed free of seminal plasma and incubated in an appropriate medium. Previous work has shown that cholesterol-enriched medium prevents sperm from becoming responsive to the inducer, progesterone. Sperm that were incubated 24 hr in cholesterol-enriched medium and then treated with progesterone showed no evidence of membrane fusion, indicating that cholesterol acts at a stage before the earliest morphological change. Inhibition of acrosomal responsiveness by cholesterol was reversible. Among other sterols reported in mammalian sperm, desmosterol and cholesterol sulfate also inhibited sperm from becoming responsive, but cholesterol palmitate did not. Our results support a model in which sperm unesterified cholesterol, or a molecule in equilibrium with it, suppresses acrosomal responsiveness. Cholesterol-enriched medium also prevented sperm from becoming responsive to the calcium/proton exchanging ionophore, ionomycin, suggesting that cholesterol's effect may be, at least in part, at a point in the signal transduction pathway subsequent to the rise in intracellular-free calcium.

76 citations


Cited by
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TL;DR: There is a dynamic interplay between pro- and anti-oxidant substances in human ejaculate and a threshold for ROS levels that may induce functional sperm ability or may lead to male infertility is unsolved.
Abstract: There is a dynamic interplay between pro- and anti-oxidant substances in human ejaculate. Excessive reactive oxygen species (ROS) generation can overwhelm protective mechanism and initiate changes in lipid and/or protein layers of sperm plasma membranes. Additionally, changes in DNA can be induced. The essential steps of lipid peroxidation have been listed as well as antioxidant substances of semen. A variety of detection techniques of lipid peroxidation have been summarized together with the lipid components of sperm membranes that can be subjected to stress. It is unsolved, a threshold for ROS levels that may induce functional sperm ability or may lead to male infertility.

601 citations

Journal ArticleDOI
TL;DR: Dynamics in adhesive and fusion properties, molecular composition and architecture of the sperm plasma membrane, as well as membrane derived signalling are reviewed.

580 citations

Journal ArticleDOI
TL;DR: The data indicate that the human epididymis plays an important role in sperm maturation but has unique properties compared with animal models, and new insights that ultimately could improve human health are provided.
Abstract: Background The epididymis performs an important role in the maturation of spermatozoa including their acquisition of progressive motility and fertilizing ability. However, the molecular mechanisms that govern these maturational events are still poorly defined. This review focuses on recent progress in our understanding of epididymal function including its development, role of the luminal microenvironment in sperm maturation, regulation and novel mechanisms the epididymis utilizes to carry out some of its functions. Methods A systematic search of Pubmed was carried out using the search term 'epididymis'. Articles that were published in the English language until the end of August 2008 and that focused on the specific topics described above were included. Additional papers cited in the primary reference were also included. Results While the majority of these findings were the result of studies in animal models, recent studies in the human epididymis are also presented including gene profiling studies to examine regionalized expression in normal epididymides as well as in those from vasectomized patients. Conclusions Significant progress has been made in our understanding of epididymal function providing new insights that ultimately could improve human health. The data also indicate that the human epididymis plays an important role in sperm maturation but has unique properties compared with animal models.

515 citations

Journal ArticleDOI
TL;DR: In this article, the authors reviewed aspects of sperm cryopreservation paralleled by events of capacitation and evaluated the possible roles of sperm membrane cholesterol, reactive oxygen species, and seminal plasma as mediators of sperm function.

488 citations

Journal ArticleDOI
TL;DR: Capacitation in vitro has been accomplished using cauda and/or ejaculated sperm incubated under a variety of conditions in defined media that mimic the electrolyte composition of the oviduct fluid, and the action of these media components to promote capacitation at the molecular level is poorly understood.
Abstract: After leaving the testis, mammalian spermatozoa from many species are morphologically differentiated but have acquired neither progressive motility nor the ability to fertilize a metaphase II-arrested egg. During epididymal transit, sperm acquire the ability to move progressively; however, they are still fertilization incompetent. Fertilization capacity is gained after residence in the female tract for a finite period of time. The physiological changes that confer on the sperm the ability to fertilize are collectively called ‘‘capacitation.’’ Capacitation was first described and defined independently by Chang [1, 2] and Austin [3, 4]. The definition of this poorly understood phenomenon has been modified and narrowed over the years. Although fertilization still represents the benchmark endpoint of a capacitated sperm, the ability of the sperm to undergo a regulated acrosome reaction (e.g., in response to the zona pellucida) can be taken as an earlier, upstream endpoint of this extratesticular maturational event. It must be stressed at this point that capacitation is also correlated with changes in sperm motility patterns, designated as sperm hyperactivation, in a number of species [5, 6]. There are examples of cases in which capacitation and hyperactivation can be dissociated experimentally [7], but one cannot yet argue that hyperactivation of motility represents an event completely independent of the capacitation process [6]. Therefore, when one attempts to understand the process of capacitation at the molecular level, it is necessary to consider events occurring both in the head (i.e., acrosome reaction) and in the tail (i.e., motility changes). The physiological site of capacitation in vivo is the oviduct or the uterus, depending on the species [5]. However, capacitation in vitro has been accomplished using cauda and/or ejaculated sperm incubated under a variety of conditions in defined media that mimic the electrolyte composition of the oviduct fluid. In most cases, these media contain energy substrates such as pyruvate, lactate, and glucose (depending on the species); a protein source that usually is serum albumin; NaHCO3; and Ca21. The action of these media components to promote capacitation at the molecular level is poorly understood and will be discussed in this review. This review is not intended to provide an ex-

470 citations