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Secretory mouse quiescin sulfhydryl oxidase 1 aggregates defected human and mouse spermatozoa in vitro and in vivo.

ABSTRACT: A flavin-dependent enzyme quiescin Q6 sulfhydryl oxidase 1 (QSOX1) catalyzes the oxidation of thiol groups into disulfide bonds. QSOX1 is prominently expressed in the seminal plasma. However, its role in male reproduction is elusive. Here, we purified the secreted form of QSOX1, i.e., QSOX1c, from mouse seminal vesicle secretions and revealed for the first time its function involved in sperm physiology. Exogenous addition of QSOX1c time-dependently promoted the in vitro aggregation of thiol-rich, oxidative stressed, and apoptotic mouse and human sperm cells. Also, in vivo aggregated sperm cells collected from mouse uterine and human ejaculates also showed high levels of QSOX1c, intracellular reactive oxygen species, annexin V, and free thiols. In summary, our studies demonstrated that QSOX1c could agglutinate spermatozoa susceptible to free radical attack and apoptosis. This characteristic may provide an opportunity to separate defective sperm cells and improve sperm quality before artificial insemination in humans and animals.

SUBMITTER: Wang TE

PROVIDER: S-EPMC8506963 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Secretory mouse quiescin sulfhydryl oxidase 1 aggregates defected human and mouse spermatozoa in vitro and in vivo.

Wang Tse-En TE Yeh Ling-Yu LY Kuo-Kuang Lee Robert R Lu Chung-Hao CH Yang Tsung-Hsien TH Kuo Yu-Wen YW Joshi Radhika R Tsai Pei-Shiue PS Li Sheng-Hsiang SH

iScience 20210925 10

A flavin-dependent enzyme quiescin Q6 sulfhydryl oxidase 1 (QSOX1) catalyzes the oxidation of thiol groups into disulfide bonds. QSOX1 is prominently expressed in the seminal plasma. However, its role in male reproduction is elusive. Here, we purified the secreted form of QSOX1, i.e., QSOX1c, from mouse seminal vesicle secretions and revealed for the first time its function involved in sperm physiology. Exogenous addition of QSOX1c time-dependently promoted the in vitro aggregation of thiol-rich ...[more]

PMID: 34667943

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Project description:BackgroundThe enzyme family Quiescin Sulfhydryl Oxidase (QSOX) is defined by the presence of an amino-terminal thioredoxin-fold (Trx) domain and a carboxy-terminal Erv family sulfhydryl oxidase domain. QSOX enzymes, which generate disulfide bonds and transfer them to substrate proteins, are present in a wide variety of eukaryotic species including metazoans and plants, but are absent from fungi. Plant and animal QSOXs differ in their active-site amino acid sequences and content of non-catalytic domains. The question arises, therefore, whether the Trx-Erv fusion has the same mechanistic significance in all QSOX enzymes, and whether shared features distinguish the functional domains of QSOX from other instances in which these domains occur independently. Through a study of QSOX phylogeny and an analysis of QSOX sequence diversity in light of recently determined three-dimensional structures, we sought insight into the origin and evolution of this multi-domain redox alliance.ResultsAn updated collection of QSOX enzymes was used to confirm and refine the differences in domain composition and active-site sequence motif patterns of QSOXs belonging to various eukaryotic phyla. Beyond the expected phylogenetic distinction of animal and plant QSOX enzymes, trees based on individual redox-active QSOX domains show a particular distinction of the Trx domain early in plant evolution. A comparison of QSOX domains with Trx and Erv domains from outside the QSOX family revealed several sequence and structural features that clearly differentiate QSOXs from other enzymes containing either of these domains. Notably, these features, present in QSOXs of various phyla, localize to the interface between the Trx and Erv domains observed in structures of QSOX that model interdomain redox communication.ConclusionsThe infrastructure for interdomain electron relay, previously identified for animal and parasite QSOXs, is found broadly across the QSOX family, including the plant enzymes. We conclude that the conserved three-dimensional framework of the QSOX catalytic domains accommodates lineage-specific differences and paralog diversification in the amino acid residues surrounding the redox-active cysteines. Our findings indicate that QSOX enzymes are characterized not just by the presence of the two defining domain folds but also by features that promote coordinated activity.

Project description:BackgroundTransmission-blocking vaccines (TBVs) can effectively prevent the community's spread of malaria by targeting the antigens of mosquito sexual stage parasites. At present, only a few candidate antigens have demonstrated transmission-blocking activity (TBA) potential in P. vivax. Quiescin-sulfhydryl oxidase (QSOX) is a sexual stage protein in the rodent malaria parasite Plasmodium berghei and is associated with a critical role in protein folding by introducing disulfides into unfolded reduced proteins. Here, we reported the immunogenicity and transmission-blocking potency of the PvQSOX in P. vivax.Methods and findingsThe full-length recombinant PvQSOX protein (rPvQSOX) was expressed in the Escherichia coli expression system. The anti-rPvQSOX antibodies were generated following immunization with the rPvQSOX in rabbits. A parasite integration of the pvqsox gene into the P. berghei pbqsox gene knockout genome was developed to express full-length PvQSOX protein in P. berghei (Pv-Tr-PbQSOX). In western blot, the anti-rPvQSOX antibodies recognized the native PvQSOX protein expressed in transgenic P. berghei gametocyte and ookinete. In indirect immunofluorescence assays, the fluorescence signal was detected in the sexual stages, including gametocyte, gamete, zygote, and ookinete. Anti-rPvQSOX IgGs obviously inhibited the ookinetes and oocysts development both in vivo and in vitro using transgenic parasites. Direct membrane feeding assays of anti-rPvQSOX antibodies were conducted using four field P. vivax isolates (named isolates #1-4) in Thailand. Oocyst density in mosquitoes was significantly reduced by 32.00, 85.96, 43.52, and 66.03% with rabbit anti-rPvQSOX antibodies, respectively. The anti-rPvQSOX antibodies also showed a modest reduction of infection prevalence by 15, 15, 20, and 22.22%, respectively, as compared to the control, while the effect was insignificant. The variation in the DMFA results may be unrelated to the genetic polymorphisms. Compared to the P.vivax Salvador (Sal) I strain sequences, the pvqsox in isolate #1 showed no amino acid substitution, whereas isolates #2, #3, and #4 all had the M361I substitution.ConclusionsOur results suggest that PvQSOX could serve as a potential P. vivax TBVs candidate, which warrants further evaluation and optimization.

Dataset Information

Secretory mouse quiescin sulfhydryl oxidase 1 aggregates defected human and mouse spermatozoa in vitro and in vivo.

Publications

Secretory mouse quiescin sulfhydryl oxidase 1 aggregates defected human and mouse spermatozoa in vitro and in vivo.

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