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PubMed2004

Hemodynamic effects of the nitric oxide donor DETA/NO in mice.

(Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA/NO) is a recently synthesized member of NO-releasing, polyamine zwitterions, the so-called NONOates, that spontaneously liberate NO in aqueous solutions. The aim of this study was to determine the hemodynamic effects of DETA/ NO in normotensive and hypertensive mice. Male Swiss Outbred mice were implanted with TA11PA-C20 blood pressure devices (Data Sciences International, USA). After recovery (7-10 days), blood pressure was monitored for 10 days while mice were receiving saline (0.1 ml/20 g/day, s.c.). Mice were then treated every four hours for 1 day with either DETA/NO 60 mg/kg i.p. or the inactive metabolite, diethylenetriamine 38 mg/kg (molar equivalent) i.p. After a 2 week wash-out period, mice were treated with adrenocorticotrophic hormone (ACTH: 500 microg/kg/day, s.c.) for 10 days and re-challenged with DETA/NO or diethylenetriamine. Results were expressed as mean +/- SEM. After 10 days of saline treatment, baseline systolic and diastolic blood pressure (BP) were similar for animals subsequently receiving DETA/NO or the amine (123 +/- 1/95 +/- 3 and 124 +/- 1/92 +/- 0.2 mmHg) respectively. DETA/NO induced a profound fall in BP [Systolic: 74 +/- 4 mmHg (-40 +/- 3%); Diastolic: 46 +/- 4 mmHg (-52 +/- 4%)] and an increase in heart rate [729 +/- 33 bpm (32 +/- 2%)] within the first 80 minutes. Diethylenetriamine had no effect. ACTH treatment increased BP in both groups (137 +/- 16/108 +/- 12 and 161 +/- 1/142 +/- 1 mmHg) respectively. DETA/ NO induced a profound fall in blood pressure [Systolic: 92 +/- 11 mmHg (-32 +/- 7%); Diastolic: 68 +/- 10 mmHg (-35 +/- 10%)] and an increase in heart rate [613 +/- 36 bpm (18 +/- 6%)] within the first 80 minutes. Again diethylenetriamine had no significant effect. There was no significant effect on body weight with any treatment. Thus DETA/NO has potent blood pressure lowering effects in both normotensive and hypertensive mice.

Adrenocorticotropic Hormone↗

PubMed2003

Spatial and temporal expression of heparan sulfate in mouse development regulates FGF and FGF receptor assembly.

Heparan sulfate (HS) interacts with diverse growth factors, including Wnt, Hh, BMP, VEGF, EGF, and FGF family members, and is a necessary component for their signaling. These proteins regulate multiple cellular processes that are critical during development. However, a major question is whether developmental changes occur in HS that regulate the activity of these factors. Using a ligand and carbohydrate engagement assay, and focusing on FGF1 and FGF8b interactions with FGF receptor (FR)2c and FR3c, this paper reveals global changes in HS expression in mouse embryos during development that regulate FGF and FR complex assembly. Furthermore, distinct HS requirements are identified for both complex formation and signaling for each FGF and FR pair. Overall, these results suggest that changes in HS act as critical temporal regulators of growth factor and morphogen signaling during embryogenesis.

Animals↗

PubMed2002

Aquaporin deletion in mice reduces intraocular pressure and aqueous fluid production.

Aquaporin (AQP) water channels are expressed in the eye at sites of aqueous fluid production and outflow: AQP1 and AQP4 in nonpigmented ciliary epithelium, and AQP1 in trabecular meshwork endothelium. Novel methods were developed to compare aqueous fluid dynamics in wild-type mice versus mice lacking AQP1 and/or AQP4. Aqueous fluid production was measured by in vivo confocal microscopy after transcorneal iontophoretic introduction of fluorescein. Intraocular pressure (IOP), outflow, and anterior chamber compliance were determined from pressure measurements in response to fluid infusions using micropipettes. Aqueous fluid volume and [Cl(-)] were assayed in samples withdrawn by micropipettes. In wild-type mice (CD1 genetic background, age 4-6 wk), IOP was 16.0 +/- 0.4 mmHg (SE), aqueous fluid volume 7.2 +/- 0.3 microl, fluid production 3.6 +/- 0.2 microl/h, fluid outflow 0.36 +/- 0.06 microl/h/mmHg, and compliance 0.036 +/- 0.006 microl/mmHg. IOP was significantly decreased by up to 1.8 mmHg (P < 0.002) and fluid production by up to 0.9 microl/h in age/litter-matched mice lacking AQP1 and/or AQP4 (outbred CD1 and inbred C57/bl6 genetic backgrounds). However, AQP deletion did not significantly affect outflow, [Cl(-)], volume, or compliance. These results provide evidence for the involvement of AQPs in intraocular pressure regulation by facilitating aqueous fluid secretion across the ciliary epithelium. AQP inhibition may thus provide a novel approach for the treatment of elevated IOP.

Animals↗

PubMed2002

Thyroid-stimulating monoclonal antibodies.

Thyrotropin (TSH) receptor monoclonal antibodies (TSHR mAbs) were obtained from cDNA-immunized NMRI mice. Three mAb immunoglobulin Gs (IgGs) (TSmAbs 1-3) that had distinct V(H )and V(L) region sequences stimulated cyclic adenosine monophosphate (cAMP) production in isolated porcine thyroid cells greater than 10x basal and as little as 20 ng/mL (0.13 nmol/L) of TSmAb 1 IgG caused a 2x basal stimulation. TSmAb 1 and 2 Fab fragments were also effective stimulators and thyroid-stimulating activities of the IgGs and Fabs were confirmed using TSHR transfected Chinese hamster ovary (CHO) cells. The TSmAbs also inhibited (125)I-labeled TSH binding to TSHR-coated tubes by 50% or more at concentrations of 1 microg/mL or less and gave 15%-20% inhibition at 20-50 ng/mL. (125)I-labeled TSmAbs bound to TSHR-coated tubes with high affinity (approximately 10(10) L/mol) and this binding was inhibited by TSHR autoantibodies with both TSH agonist and antagonist activities. Inhibition of labeled TSmAb binding by Graves' sera correlated well with inhibition of TSH binding (r = 0.96; n = 18; p < 0.001 for TSmAb 2). The TSmAbs have considerable potential as (1) new probes for TSHR structure-function studies, (2) reagents for new assays for TSHR autoantibodies, and (3) alternatives to recombinant TSH in various in vivo applications.

Animals↗

PubMed2002

Characterization of the thyrotropin binding pocket.

A panel of monoclonal antibodies (mAbs) to the thyrotropin receptor (TSHR) was prepared using three different immunization strategies. The mAbs obtained (n = 138) reacted with linear epitopes covering most of the TSHR extracellular domain and with conformational epitopes. mAbs that bound to five different regions of the TSHR (amino acids [aa] 32-41, aa 36-42, aa 246-260, aa 277-296, and aa 381-385) were able to inhibit (125)I-labeled thyrotropin (TSH) binding to solubilized TSHR preparations. Fab and immunoglobulin G (IgG) preparations were similarly effective inhibitors for mAbs reactive with aa 246-260, aa 277-291 and aa 381-385 suggesting that these three regions of the TSHR are involved in TSH binding. In contrast mAbs reactive with aa 32-41 and aa 36-42 were not effective at inhibiting TSH binding when Fab preparations were used, suggesting that these N terminal regions of the TSHR were less critical for TSH binding. Our studies suggest that three distinct and discontinuous regions of the TSHR (aa 246-260 and 277-296 on the TSHR A subunit) and aa 381-385 (on the TSHR B subunit) fold together to form a complex TSH binding pocket. Alignment of the aa sequences of these three regions in TSHRs from different species indicates that they are highly conserved.

Animals↗

PubMed2004

Progression from frontal-parietal to mesial-temporal epilepsy after fluid percussion injury in the rat.

We recently described an in vivo model of post-traumatic epilepsy (PTE) in the rat where chronic spontaneous recurrent seizures appear following a single episode of fluid percussion injury (FPI). PTE, studied during the first 2 months post-injury, was focal and seizures originated predominantly from the frontal-parietal neocortex at or around the injury site. However, rarer bilateral seizures originating from a different and undefined focus were also observed. To shed light on the Posttraumatic Epileptogenic mechanisms and on the generation of bilateral seizures, we studied rats up to 7 months post-injury. In vivo paired epidural and depth-electrode recordings indicated that the anterior hippocampus evolves into an epileptic focus which initiates bilateral seizures. The rate of frontal-parietal seizures remained constant over time after 2 weeks post-injury, while the rate of hippocampal seizures greatly increased over time, suggesting that different mechanisms mediate neocortical and hippocampal post-traumatic epileptogenesis. Because of different temporal evolution of these foci, the epileptic syndrome was characterized by predominant frontal-parietal seizures early after injury, but by predominant mesio-temporal seizures at later time points. Pathological analysis demonstrated progressive hippocampal and temporal cortex pathology that paralleled the increase in frequency and duration of bilateral seizures. These results demonstrate that FPI-induced frontal-parietal epilepsy (FPE) progresses to mesial-temporal lobe epilepsy (MTLE) with dual pathology. These observations establish numerous similarities between FPI-induced and human PTE and further validate it as a clinically relevant model of PTE.

Animals↗

PubMed2002

Application of the false discovery rate to quantitative trait loci interval mapping with multiple traits.

Controlling the false discovery rate (FDR) has been proposed as an alternative to controlling the genome-wise error rate (GWER) for detecting quantitative trait loci (QTL) in genome scans. The objective here was to implement FDR in the context of regression interval mapping for multiple traits. Data on five traits from an F2 swine breed cross were used. FDR was implemented using tests at every 1 cM (FDR1) and using tests with the highest test statistic for each marker interval (FDRm). For the latter, a method was developed to predict comparison-wise error rates. At low error rates, FDR1 behaved erratically; FDRm was more stable but gave similar significance thresholds and number of QTL detected. At the same error rate, methods to control FDR gave less stringent significance thresholds and more QTL detected than methods to control GWER. Although testing across traits had limited impact on FDR, single-trait testing was recommended because there is no theoretical reason to pool tests across traits for FDR. FDR based on FDRm was recommended for QTL detection in interval mapping because it provides significance tests that are meaningful, yet not overly stringent, such that a more complete picture of QTL is revealed.

Animals↗

PubMed2002

Estimation of deleterious genomic mutation parameters in natural populations by accounting for variable mutation effects across loci.

The genomes of all organisms are subject to continuous bombardment of deleterious genomic mutations (DGM). Our ability to accurately estimate various parameters of DGM has profound significance in population and evolutionary genetics. The Deng-Lynch method can estimate the parameters of DGM in natural selfing and outcrossing populations. This method assumes constant fitness effects of DGM and hence is biased under variable fitness effects of DGM. Here, we develop a statistical method to estimate DGM parameters by considering variable mutation effects across loci. Under variable mutation effects, the mean fitness and genetic variance for fitness of parental and progeny generations across selfing/outcrossing in outcrossing/selfing populations and the covariance between mean fitness of parents and that of their progeny are functions of DGM parameters: the genomic mutation rate U, average homozygous effect s, average dominance coefficient h, and covariance of selection and dominance coefficients cov(h, s). The DGM parameters can be estimated by the algorithms we developed herein, which may yield improved estimation of DGM parameters over the Deng-Lynch method as demonstrated by our simulation studies. Importantly, this method is the first one to characterize cov(h, s) for DGM.

Animals↗

PubMed2006

Hepatocellular apoptosis during Candida albicans colonization: involvement of TNF-alpha and infiltrating Fas-L positive lymphocytes.

The liver constitutes the first barrier in the control of hematogenous dissemination of Candida albicans of intestinal origin. In rats infected with C. albicans, this organ limits the growth of the yeast and mounts an efficient inflammatory reaction. However, in rats infected and exposed to chronic varied stress, the hepatic inflammatory reaction is compromised and the outcoming of the infection is more severe. Although in both groups the fungal burden is associated with hepatotoxicity, steatosis, increment of hepatic enzymes and lipid peroxidation, stress-related differences are clearly evident. Herein, we evaluated in infected and infected-stressed hosts the involvement of apoptosis and pro-apoptotic signals in the hepatic injury during the acute step of C. albicans infection. We studied in situ apoptosis by 4',6-diamidino-2-phenylindole dihydrochloride and terminal deoxynucleotidyl transferase dUTP nick-end labeling reactions, the levels of local tumor necrosis factor (TNF)-alpha mRNA by reverse transcription-PCR and the Fas/Fas-L expression by immunohistochemistry and western blot. We also purified intrahepatic lymphocytes (IHLs) to evaluate the dynamic of recruitment following the infection and to characterize the in vivo and in vitro interaction of C. albicans with this subset evaluating the kinetic of Fas-L and Toll-like receptor-2 (TLR-2) expression. This work shows, for the first time, the occurrence of in situ apoptosis of hepatocytes as well as the kinetic of IHL recruitment early during the C. albicans infection. Moreover, our results demonstrate the ability of the fungus to up-regulate the Fas-L and TLR-2 expression in this subset. In the scenario of early liver injury, the recruited IHLs and the modulated expression of TNF-alpha, Fas-L and TLR-2 molecules could act coordinately in delivering death signals.

Animals↗

PubMedDate not supplied

Karyotype identity of two subspecies of Eld's deer [Cervus eldi (Cervinae, Artiodactyla)] and its consequences for conservation.

Among the three subspecies generally recognized within the Eld's deer (Cervus eldi)--C. e. eldi, C. e. thamin, and C. e. siamensis--C. e. siamensis is considered to be particularly endangered following its disappearance from a major portion of its original range. The only captive breeding population of this subspecies is in the zoological parks at the Paris Museum of Natural History. Taking into account its low effective population size (Ne = 7) and the increasing levels of inbreeding, the continued breeding of this "micropopulation" in isolation from closely related subspecies and in particular from C. e. thamin, which is much more common in zoos as well as in the nature, is questioned. As an initial step in determining if crosses between these subspecies could be performed without risk of outbreeding depression due, in part, to gross differences in their karyotypes, a comparative chromosome banding analysis (RBG-bands) of C. e. siamensis and C. e. thamin was undertaken. No chromosomal differences were identified between the taxa at the level of resolution obtained. The study suggests that, at least from a karyotypic perspective, no obvious differences delimit the two subspecies, and hybridization between endangered C. e. siamensis and C. e. thamin is not likely to lead to impaired fertility in hybrid animals.

Animals↗

PubMedDate not supplied

Alternative mating strategies in Atlantic salmon and brown trout.

By screening variable number of tandem repeat (VNTR) loci, multiple paternity within clutches has been found in wild populations of southern European Atlantic salmon (Salmo salar) and brown trout (Salmo trutta). For Atlantic salmon, we determined the relative contribution of alternative male phenotypes to the next generation. Individual males that are morphologically juvenile yet sexually mature fertilized a large proportion of eggs, and they thereby contributed to an increase of genetic variability in wild populations via (1) balancing the sex ratio, (2) increasing outbreeding, and (3) enlarging the effective population size, in part a consequence of (1) and (2). In addition, these precocious males ensured that interspecific spawns involving Atlantic salmon females and brown trout males (a fairly common occurrence in southern Europe where the two species are sympatric) resulted mostly in Atlantic salmon progeny. For brown trout, preliminary genetic results indicated that multiple paternity, when present, was not due to alternative mating strategies by males, but rather to successive fertilizations by adult suitors.

Animals↗

PubMed2003

In vivo genotoxicity studies with 3-monochloropropan-1,2-diol.

3-Monochloropropan-1,2-diol (3-MCPD) is a contaminant of polyamine flocculants used in the production of drinking water, but more significantly for human exposure it can arise also in certain foodstuffs containing acid-hydrolysed vegetable protein. It is carcinogenic in the rat, producing tumours in males in the testes, mammary gland and the preputial gland and also kidney tumours in both sexes. It has given positive results in in vitro mutagenicity studies, but there have been no satisfactorily conducted in vivo studies in somatic cells published in the peer reviewed literature. As a result, and because of the absence of appropriate in vivo evidence, several international regulatory agencies had previously judged it prudent to assume that 3-MCPD possessed mutagenic activity in vivo and considered 3-MCPD to be a genotoxic carcinogen. We present in this paper results from two in vivo mutagenicity studies with 3-MCPD, namely a bone marrow micronucleus test in the rat and unscheduled DNA synthesis in the rat liver, both conducted in accordance with relevant OECD protocols. These studies show that 3-MCPD does not possess genotoxic activity in vivo in the tissues examined. On the basis of these findings, and along with evidence that tumours may be induced by mechanisms involving either hormonal disturbances or sustained cytotoxicity, we believe that 3-MCPD may now be considered to be carcinogenic to rodents via a non-genotoxic mechanism.

Animals↗

PubMed2001

Screening for highly heterozygous chickens in outbred commercial broiler lines to increase detection power for mapping quantitative trait loci.

Two commercial broiler lines were used in an experiment to map quantitative trait loci (QTL) affecting disease resistance. Chickens from these lines were genotyped with 27 microsatellite markers to estimate heterozygosity and polymorphism information content (PIC), the probability that one parent is heterozygous at a marker locus and the other has a different genotype. Heterozygosity estimated from allelic frequencies was 0.52 for the two lines; however, heterozygosity calculated from actual counts of heterozygous loci was much lower (0.36) than the estimated heterozygosity. The PIC was 0.45 in these lines, and average allele number per marker locus was about 3.5. Twenty-five males produced from a cross between these two lines were screened with the DNA markers to select birds with high heterozygosity at marker loci. Mating simulation showed that uninformative matings could be reduced by about 5% if 12 pairs of males and females with the highest heterozygosity at marker loci were selected, which was about a 25% reduction in total uninformative matings. This experiment demonstrated that the heterozygosity and PIC in commercial broiler lines were low and selection for the birds with high heterozygosity at marker loci could increase informative content in chickens used in the experiments of QTL mapping, thus increasing detection power for QTL mapping.

Animal Husbandry↗

PubMed2004

Glutathione depletion is a major determinant of inhaled naphthalene respiratory toxicity and naphthalene metabolism in mice.

Naphthalene (NA) is metabolized to highly reactive intermediates that are primarily detoxified by conjugation to glutathione (GSH). Intraperitoneal administration of naphthalene causes substantial loss of both hepatic and respiratory GSH, yet only respiratory tissues are injured in mice. The liver supplies GSH to other organs via the circulation, making it unclear whether respiratory GSH losses reflect in situ respiratory depletion or decreased hepatic supply. To address this concern, mice were exposed to naphthalene by inhalation (1.5-15 ppm; 2-4 h), thereby bypassing first-pass hepatic involvement. GSH levels and histopathology were monitored during the first 24 h after exposure. Half of the mice were given the GSH depletor diethylmaleate (DEM) 1 hour before naphthalene exposure. Lung and nasal GSH levels rapidly decreased (50-90%) in mice exposed to 15 ppm naphthalene, with cell necrosis throughout the respiratory tract becoming evident several hours later. Conversely, 1.5 ppm naphthalene caused moderate GSH loss and only injured the nasal olfactory epithelium. Neither naphthalene concentration depleted hepatic GSH. Animals pretreated with DEM showed significant GSH loss and injury in nasal and intrapulmonary airway epithelium at both naphthalene concentrations. DEM treatment, perhaps by causing significant GSH loss, decreased water-soluble naphthalene metabolite formation by 48% yet increased NA-protein adducts 193%. We conclude that (1) GSH depletion occurs in airways independent of hepatic function; (2) sufficient GSH is not supplied by the liver to maintain respiratory GSH pools, or to prevent injury from inhaled naphthalene; and (3) GSH loss precedes injury and increases protein adduct formation.

Administration, Inhalation↗

PubMed2005

The endocrine disruptor atrazine accounts for a dimorphic somatostatinergic neuronal expression pattern in mice.

It has now been established that a large number of man-made and natural chemicals are capable of interfering with the action of natural hormones. In this category "endocrine disruptors" such as the herbicide atrazine, when administered at ecological low doses (1 or 100 microg/kg per day) from gestational day 14 to postnatal day 21, provided a clear dimorphic neurodegenerative pattern in some brain areas of the domestic mouse (Mus musculus). Indeed, the high concentration (100 microg/kg per day) with respect to the low concentration (1 microg/kg per day) induced relevant neuronal damage in extrahypothalamic sites, such as the cortical and striatal areas in both sexes. Marked alterations in other areas, including the hippocampal and hypothalamic nuclei, were mostly typical of the female. At the neuronal level, the neuropeptide somatostatin, specific for the secretion of growth hormone, seemed to be a major target of atrazine effects, as demonstrated by evident subtype2,3,5 receptor mRNA differences of this neuropeptide, at least for the first two subtypes. In particular, a very strong (p < 0.001) upregulation of subtype2 expressing neurons was detected in female hypothalamic areas, specifically the suprachiasmatic nucleus, whereas a similar downregulatory trend was reported for some extrahypothalamic areas such as the striatum. Interestingly, very strong upregulatory and downregulatory actions were detected for neurons expressing subtype3 in male hypothalamic and amygdalar regions and in the cortical and hippocampal areas, respectively. Overall, it appears that these first neurotoxicological effects of atrazine are very likely linked to dimorphic expression patterns of specific somatostatin subtypes in discrete but key hypothalamic and extrahypothalamic areas of Mus musculus.

Animals↗

PubMed2002

Osmotic characteristics of mouse spermatozoa in the presence of extenders and sugars.

Successful cryopreservation requires cells to tolerate volume excursions experienced during permeating cryoprotectant equilibration and during cooling and warming. However, prior studies have demonstrated that mouse spermatozoa are extremely sensitive to osmotically induced volume changes. A series of three experiments were conducted 1) to test the efficacy of two commonly used extender media components, egg yolk (EY) and skim milk (SM), in broadening the osmotic tolerance limits (OTL) of ICR and B6C3F1 murine spermatozoa; 2) to determine if the extender components affected sperm plasma membrane permeability coefficients for water and cryoprotective agent (CPA) characteristics; and 3) to test the effects of permeating and nonpermeating CPA on mouse sperm morphology. In experiment 1, sperm samples were added to 150, 225, 300, 450, or 600 mOsm NaCl, EY, SM, sucrose, or choline chloride at 22 degrees C and then returned to isosmotic conditions. In experiment 2, epididymal sperm were preequilibrated in 1 M glycerol (Gly) or 2 M ethylene glycol (EG) prepared in SM extender, abruptly exposed to isosmotic conditions at 22, 15, or 2 degrees C, and the corresponding volume excursions were measured and analyzed. In experiment 3, the effects of permeating CPA (0.3 M EG or dimethyl sulfoxide) or nonpermeating CPA (12% sucrose or 18% raffinose) on sperm morphology (i.e., principle midpiece folding and putative membrane fusion) were evaluated. Experiment 1 showed that spermatozoa from ICR and B6C3F1 mice have effectively broader OTL when exposed to EY or SM extenders. The results of experiment 2 indicated that, for ICR sperm, the activation energy (E(a)) for the hydraulic conductivity (L(p)) was unchanged in SM extender. However, for B6C3F1 sperm, there were significant differences in E(a) of L(p) in the presence of Gly and EG. The result of experiment 3 indicated that permeating CPAs damage sperm membrane integrity, causing a high frequency of head-to-tail or tail-to-tail membrane fusion, whereas this occurrence in the presence of nonpermeating CPA was less than 3%. Finally, the results of experiments 1 and 2 were combined in a mathematical model to predict Gly and EG addition and removal in the presence of SM extender, which would prevent mouse sperm membrane damage. These predictions indicated that, for ICR sperm, both Gly and EG may be added and removed in a single step. However, for B6C3F1 spermatozoa, Gly required a two-step addition while EG only required a single step. For removal from B6C3F1 sperm, Gly required a three-step removal process while EG required a two-step removal.

Animals↗

PubMed2003

Distinction of sperm-binding site and reactive site for trypsin inhibition on p12 secreted from the accessory sex glands of male mice.

Six variants of P12, a Kazal-type trypsin inhibitor in the secretion of male mouse accessory sexual glands, were made using single-site mutations including R19L, Y21V, D22G, R43G, K44S, and R45T, based on one-letter-code mutation of amino acids. The other two variants, Nd10 and Cd8, were made using the deletion of 10 and 8 residues from the N- and C-terminals, respectively. Their CD profiles revealed maintenance of the P12 conformation in the seven variants, excluding Cd8, which became unfolded. Only R19L entirely lost the ability while the other variants were as strong as P12 in inhibiting the trypsin digestion of N-benzoyl-Phe-Val-Arg 7-amido-4-methylcoumarin. The immunocytochemical results demonstrated that D22G and Cd8 failed to bind to sperm, Y21V very weakly did so, and the other variants retained their sperm-binding abilities. Concomitantly, the immunocytochemical stainability of each ligand was parallel to its inhibitory effect on 125I-P12-sperm binding, and a synthetic oligopeptide corresponding to residues 18-24 of P12 was able to inhibit P12-sperm binding. The data together concluded that R19 was essential for protease inhibition and D22 and/or Y21 mainly being responsible for the binding of P12 to sperm. The steric arrangement of R19, Y21, and D22 on the tertiary structure of P12 is discussed.

Amino Acid Sequence↗

PubMed2004

Sperm-induced modification of the oviductal gene expression profile after natural insemination in mice.

In mammals, the physiological interaction between spermatozoa and oviductal epithelia involves intimate and specific contact between the two cell types. Spermatozoa may undergo stringent selection processes within the female reproductive tract before they meet and fertilize oocytes. The physiological basis of the sperm selection process is largely unknown. Here we tested the hypothesis that the oviduct has a recognition system for spermatozoa that can detect the arrival of spermatozoa in the oviduct after insemination, resulting in alterations of the oviductal transcriptome. We initially performed a global screening of the oviductal transcriptome in mice 1) at the time of estrus (mating) and 2) 6 h after mating. Transcriptional alterations in the oviduct after mating were attributed to the presence of spermatozoa in the oviduct after mating and also to changes in the hormonal environment as female mice underwent the transition from estrus to diestrus. To distinguish these possibilities, female mice were then mated with T145H mutant mice, which because of spermatogenic arrest, produce seminal plasma but no spermatozoa. Focusing on two molecules that in the first experiment were upregulated after mating, it was found that adrenomedullin and prostaglandin endoperoxidase synthase 2 transcripts were upregulated in the oviducts of mice only after mating with fertile males; those mated with T145H infertile males showed significantly less response. These results indicate that it is the arrival of spermatozoa in the oviduct that activates one or more signal transduction pathways and leads to changes in the oviductal transcriptome profiles.

Adrenomedullin↗