Biomedical subjects

M C Maurel

Publications and source records attributed to M C Maurel.

At least 19 recordsLinked to original sources

PubMed2007

Transferrin overexpression alters testicular function in aged mice.

Many studies have shown a correlation between transferrin (Tf) concentration and sperm yield in several mammalian species. We have used transgenic mice expressing human Tf (hTf) to investigate if overexpression of Tf increases the efficiency of mouse spermatogenesis. We demonstrated that a 36% increase of Tf does not ameliorate the efficiency of mouse spermatogenesis but on the contrary resulted in a 36% decrease of testis sperm reserves. Tf overexpression had no effect on testicular determination and development, however testicular function of these transgenic mice was affected in an age-dependent manner. At 16 months of age, testicular and epididymal weights were significantly reduced. While spermatogenesis was qualitatively normal, testicular functions were perturbed. In fact, testosterone rate after human chorionic gonadotropin (hCG) stimulation was lower in Tf overexpressing mice. Intratesticular concentration of estradiol-17beta was increased and fluid accumulation after ligation of rete testis was more abundant in these transgenic mice. Surprisingly, we found that endogenous Tf levels were also increased in Tf overexpressing mice and we demonstrated for the first time that Tf may serve to upregulate its own expression in testis. Collectively, our data show that Tf overexpression has negative effects on testicular function and that Tf levels require strict regulation in the testis.

Animals↗

PubMed2002

RNA-acting antibiotics: in-vitro selection of RNA aptamers for the design of new bioactive molecules less susceptible to bacterial resistance.

During the last few years, antibiotic multiresistance has been increasing, not only in hospitals, but also, more worryingly, in general medicine. Different ways are being explored to bypass this problem. RNA-acting antibiotics such as aminosides (aminoglycosides) bind to bacterial RNA causing premature termination of proteins and mistranslation in bacteria. It is now possible to study the interactions of such antibiotics with their target by in-vitro selection of RNA molecules that recognize these antibiotics (RNA aptamers, SELEX method). The knowledge of the antibiotic-RNA interactions represents a promising way for the rational design of new bioactive compounds less susceptible to bacterial resistance.

Aminoglycosides↗

PubMed2001

Why biologists should support the exploration of Mars.

Physicists, chemists and geologists in the USA and Europe propose that the search for extraterrestrial life is an important justification for the exploration of Mars. Biologists, however, much more excited by the advent of the postgenome sequencing era, in general display little enthusiasm for planetary exploration. We argue that the search for traces of life on Mars represents a major thought-provoking challenge for the life sciences that should be taken up by the biological community.

Biology↗

PubMed2001

Recent findings in the modern RNA world.

It is assumed that modern life forms arose from a molecular ancestor in which RNA molecules both stored genetic information and catalyzed biochemical reactions. In modern cells, these functions are carried out, respectively, by DNA and proteins, but diverse cellular RNAs are also involved in key cellular functions. In this paper, we review the cellular RNAs that are ubiquitous and/or that perform essential biological functions, and we discuss the evolutionary relationships of such RNAs with a prebiotic RNA world. This unexpected biological diversity of cellular RNAs and the crucial functions they perform in cellular metabolism demonstrate the complexity of an RNA-driven metabolism in an ancient RNA world and in modern life. Cellular RNAs are involved in translation (tRNA and rRNA) but also in ribosome maturation (snoRNA) and more generally in RNA processing (snRNA and snoRNA), replication (telomerase RNA), editing, protein translocation (SRP RNA), cellular transport (vRNA) and translation quality control (tmRNA). In addition, the function of many other cellular RNAs has not yet been determined. Future investigations of RNA function will allow us to better understand not only early evolutionary biological processes but also the central metabolism of modern cells.

Biological Evolution↗

PubMed2000

Oligomerization of alpha-thioglutamic acid.

A decaglutamic acid primer is extended very slowly by alpha-thioglutamic acid. The addition of bicarbonate to the reaction mixture greatly accelerates the reaction. We believe the N-carboxyanhydride of glutamic acid is an intermediate in the accelerated reaction. When K3Fe(CN)6 and bicarbonate are both present in the reaction mixture, oligoglutamic acids up to at least the 15-mer are formed rapidly. The acylating agent is the oxidation product of thioglutamic acid, a diacyldisulfide.

Bicarbonates↗

PubMed1999

Copper-adenine catalyst for O(2) production from H(2)O(2).

In solutions of CuCl2 and adenine copper can be bound to adenine. Two Cu(adenine)(2) complexes [Cu(C(5)H(5)N(5))(2)]2+/Cu(C(5)H(4)N(5))(2)] are in equilibrium with free adenine. Copper-adenine complexes present a catalytic activity (e.g., H(2)O(2) disproportionation into O(2) and water) but depending on complex concentration H(2)O(2) also strongly oxidizes the adenine within the complexes. Raman spectroscopy quantifies copper-adenine complex formation and H(2)O(2) consumption; polarography quantifies O(2) production. As for C(40) catalase, optimal catalytic capacities depend on physiological conditions, such as pH and temperature. The comparative analysis of kinetic parameters shows that the affinity for H(2)O(2) of Cu(adenine)(2) is 37-fold lower than that of C(40) catalase and that the molar activity for O(2) production is 200-fold weaker for Cu(adenine)(2) than for the enzyme. In the 10(-6)-10(-3) M range, the strong decrease of activity with raising complex concentration is explained by aggregation or stacking, which protects Cu(adenine)(2) entities from H(2)O(2) oxidation, but also decreases O(2) production.

Adenine↗

PubMed1999

The negative effect of repeated equine chorionic gonadotropin treatment on subsequent fertility in Alpine goats is due to a humoral immune response involving the major histocompatibility complex.

In dairy goats, the use of eCG as a convenient hormone for the induction of ovulation is necessary for out-of-season breeding and artificial insemination. However, repeated eCG treatments are followed by decreased fertility in goats inseminated at a fixed time after treatment. In this report, we show the presence of anti-eCG antibodies in plasma of treated goats. A 500 IU eCG injection induces a humoral response, with variable concentrations of anti-eCG antibody being produced in individual goats. The analysis of successive anti-eCG immune responses over several years has demonstrated the existence of different populations of goats, defined as low, medium, and high responders. By the use of two caprine microsatellites located inside (OLADRB) and outside (BM1258) the major histocompatibility complex (MHC), a significant association (p < 0.05) between the anti-eCG antibody response and some MHC-DRB alleles was found. Goats with high antibody concentrations at the time of eCG injection (> 2.5 microg/ml) exhibited a much lower kidding rate than did other females (41.3% vs. 66.7%). Lower fertility of these goats, inseminated at a fixed time after eCG treatment, might be due to the observed delay in estrus occurrence and the preovulatory LH surge.

Animals↗

PubMed1999

Humoral immune response to equine chorionic gonadotropin in ewes: association with major histocompatibility complex and interference with subsequent fertility.

In dairy ewes, the use of eCG as a convenient hormone for the induction of ovulation is necessary for out-of-season breeding and artificial insemination (AI). In this report we show the presence of anti-eCG antibodies in plasma of treated ewes. The major histocompatibility complex (MHC) was involved in the individual variability of the humoral immune responses to eCG. We found significant associations between the anti-eCG response phenotype and some MHC class II alleles. The low immune response phenotype was associated with one MHC class II allele only in Lacaune ewes, and the high immune response phenotype was associated with one MHC class II allele both in Manech and in Lacaune ewes. In herds, the impact of residual anti-eCG antibodies on subsequent fertility after AI seems minimal because of an indirect elimination of high-responder ewes from AI breeding. Therefore, the true magnitude of the association between residual anti-eCG antibody concentration and fertility has been underestimated. An additional experiment without any high-responder female elimination showed a significant correlation between high residual antibody concentrations and lower lambing rate after AI at a fixed time, possibly because of a delayed preovulatory LH surge. The results suggest that anti-eCG antibody concentration is one risk factor for infertility after AI.

Aging↗

PubMed1999

Implications of recent advances in reproductive physiology for reproductive management of goats.

The control of reproduction in goats is interesting for technical reasons (synchronization of kiddings, adjustment to forage availability or to economy), and for genetic reasons (identification and dissemination of improved genotypes). The use of short-light rhythms leads to markedly increased production of semen per buck and prevents occurrence of a 'resting' season. Recent identification of a bulbourethral lipase in goat spermatozoa opens new perspectives in sperm preservation. Light plus 'short day' treatments also allow induction of out-of-season oestrous cycles and ovulations leading to enhanced fertility. Repeated use of eCG provokes the production of antibodies, delays the timing of ovulation and causes a reduction in fertility after fixed-time artificial insemination. All steps of embryo production, freezing and transfer are now controlled and allow the attainment of satisfactory numbers of kids born per donor female, which are compatible with the development of the technique for exchanging genotypes between countries. In vitro production of embryos allows high development rates to be achieved after in vitro maturation and fertilization of oocytes, and will ensure the production of synchronous populations of one-cell zygotes at the stage required by new biotechnologies.

Animal Husbandry↗

PubMed1998

From Panspermia to Bioastronomy, the evolution of the hypothesis of universal life.

During the 19th and early 20th centuries, ideas related to the possible origin in space of bioorganic molecules, or seeds, or even germs and organisms (and how they reached the Earth) included the Panspermia theory. Based on the idea of the eternity of life proposed by eminent physicists - such as Arrhenius and Kelvin - 'Panspermia' is mainly divided into two branches: lithopanspermia (transport of germs inside stones traveling in space) and radiopanspermia (transport of spores by radiative pressure of stellar light). We point out some arguments to help to understand whether 'Panspermia' could exist nowadays as the same theory defined one century ago. And we wonder about the kind of evolution 'Panspermia' could have undergone during only a few decades. This possible evolution of the 'Panspermia' concept takes place in the framework of the emergence of a new field, Bioastronomy. We present how this discipline has emerged during a few decades and how it has evolved. We consider its relationship with the progression of other scientific fields, and finally we examine how it is now included in different projects of space agencies. Bioastronomy researches having become more and more robust during the last few years, we emphasize several questions about new ideas and their consequences for the current hypothesis of 'Panspermia' and of universal life.

Astronomy↗

PubMed1997

Use of an immunoenzymatic assay to detect the luteinizing hormone peak in bitches.

The success of artificial insemination with fresh chilled or frozen semen depends on the time of insemination. Determination of oestrous behaviour, use of vaginal smears or measurement of the vaginal resistivity are unreliable techniques and interpretation of the dosages of progesterone may be critical as it may vary from one laboratory to another. The plasma concentration of LH displays a peak of secretion that can be a good reference to date the events of the ovarian cycle. The plasma concentration of LH was measured in ten bitches by a new sandwich immunoenzymatic assay (Reprokit, Sanofi) and results were compared with the vaginal smears and plasma concentrations of progesterone. The LH peak was easily detected and lasted 3.3 days with maximum values ranging from 10 to 22 ng ml-1. At the time of the peak, the vaginal smears displayed features of pro-oestrus and the plasma concentration of progesterone was 2.9 ng ml-1. This immunoenzymatic assay, already used for many species, is an effective tool for determining the time of the LH peak. Added to the study of the progesterone concentration, it may help to determine the optimal time for artificial inseminations, particularly when frozen semen is used.

Animals↗

PubMed1996

Follitropin action on the transferrin gene in Sertoli cells is mediated by cAMP-responsive-element-binding-protein and antagonized by chicken ovalbumin-upstream-promoter-transcription factor.

The transcription of the transferrin (Tf) gene is induced by follitropin via cAMP in rat Sertoli cells. We previously demonstrated that the cAMP-responsive-element-binding protein (CREB) interacts on the proximal region II (PRII) of the human Tf promoter (Suire et al., 1995). The PRII region is identified as essential for cAMP inducibility of the Tf promoter and contains a CCAAT box. This unexpected result led us to study the relation that exists between CREB and the PRII site. In the liver, CCAAT/enhancer-binding (C/EBP) proteins act at the PRII site. Although these factors are absent in Sertoli cells, their overexpression in Sertoli cells disturbs basal and induced transcription. C/EBP alpha and delta were able to stimulate the basal transcription driven by the -100 to +39 region, placed upstream of the chloramphenicol acetyltransferase (CAT) gene. However, only C/EBP alpha allowed the cAMP-inducible expression. The Ka of CREB bZIP (254-327), a deleted form of CREB, for the CRE site (3.92 x 10(8)M-1) and for the PRII site (1.38 x 10(8)M-1) were determined using the surface plasmon resonance (SPR) method. The Ka values were similar, although the derived kinetics were different: higher ka and kd of CREB for the PRII site were found compared with the CRE site. Since we observed important dissociation kinetics, we hypothesized that the binding of CREB to the PRII site is stabilized by CREB-binding protein (CBP) or by chicken-ovalbumin-upstream-promoter transcription factor (COUP-TF) binding to PRI site near to PRII. However, we observed that the overexpression of CBP in Sertoli cells did not potentiate the basal and cAMP-stimulated activity of CREB of the -100 to +39Tf-CAT construct. In basal and cAMP-stimulated conditions, COUP-TF appeared to repress the transcription driven by the -100 to +39 region in a specific manner. These results demonstrate a direct action of CREB on hTf promoter, which is antagonized by COUP-TF and may explain the transcriptional regulation of Tf by follitropin, via cAMP.

Animals↗

PubMed1996

The origin of kinetic cooperativity in prebiotic catalysts.

A polyallylamine carrying long hydrophobic dodecyl groups and adenine residues as side chains (PALAD C12) may be able to catalyze the hydrolysis of N-carbobenzoxy-l-alanine p-nitrophenyl ester (N-Cbz-Ala) as well as p-nitrophenyl acetate (pNPA). The progress curve of hydrolysis of the former displays a long lag and apparently no steady state. After this transient the rate falls off due to the accumulation of the products. Conversely, the hydrolysis of p-nitrophenyl acetate displays classical burst kinetics followed by a slow decline of the reaction rate.Theoretical considerations show that a steady state may be expected to occur only if the concentration of the free catalyst is very small during the reaction. This condition is sufficient to allow the rate of disappearance of the substrate to be equal to the rate of appearance of the products, which is precisely a condition for the existence of a steady state. If the catalyst is poorly active and has a loose affinity for its substrate and product, the measurement of a significant reaction rate will require a much larger concentration of the catalyst. Therefore, under these conditions, one cannot expect a steady state to occur. The mathematical expression of the error made in the steady-state assumption has been derived. This error increases with the catalyst concentration and decreases if the affinity of the substrate for the catalyst is high. Therefore the lack of steady state is associated with the affinity (or the dissociation) of the substrate and the product for the catalyst. When this affinity is low, the free concentration of the catalyst during the reaction is high and one cannot expect a steady state to occur. This is precisely what takes place with N-Cbz-Ala.A mathematical expression of the rate of hydrolysis of N-Cbz-Ala and of any reactant that displays this type of kinetics may be derived at the end of the transient when the rate is close to its maximum value. Under these conditions the rate cannot follow classical Michaelis-Menten kinetics and displays positive cooperativity. It may therefore be speculated that primordial template-like catalysts that were displaying a poor affinity for their substrates and products were already exhibiting apparent positive cooperativity in the kinetic reactions they were able to catalyze.

Alanine↗

PubMed1994

Structure-function relationships and mechanism of action of pituitary and placental gonadotrophins.

Data from the author's laboratory on relationships between structure and function of equine luteinizing hormone, follicle-stimulating hormone and choriogonadotrophin as well as their mechanisms of action are reviewed and compared with their human counterparts. Polymorphism of these hormones and problems associated with their purification are discussed as well as the association and dissociation of their alpha- and beta-subunits. The affinity of receptor binding, the superactivity of membrane transduction and homologous desensitization of target cells by non-stimulatory doses of the gonadotrophins are also reviewed.

Chorionic Gonadotropin↗

PubMed1993

N6-substituted adenine derivatives and RNA primitive catalysts.

In our search for primitive RNA catalysts, we noticed that N6-ribosyl-adenine, a compound easily synthesized under presumed prebiotic conditions, has a free imidazole group. We showed that it is, as a catalyst, a potential analogue of histidine. Furthermore, among the chemical groups involved in protein catalysis, the imidazole ring of histidine has no equivalent in the RNA world. We have synthesized aliphatic amino groups containing polymers with adenine rings linked to macromolecules by their 6-amino group. These polymers exhibit pronounced catalytic activities in the hydrolysis of p-nitrophenylacetate. We discuss here the fact that in primitive catalysis the imidazole group could have been replaced by N6-substituted adenine derivatives.

Adenine↗

PubMed1993

Topography of equine chorionic gonadotropin epitopes relative to the luteinizing hormone and follicle-stimulating hormone receptor interaction sites.

In order to localize the epitopes of equine chorionic gonadotropin (eCG) involved in interaction with luteinizing hormone (LH) and follicle-stimulating hormone (FSH) receptors, we used 14 monoclonal anti-eCG antibodies (mAbs). Different effects of these mAbs on the bioactivities of eCG were observed in in vitro bioassays, but the effects of each mAb on the two bioactivities were similar for all but four mAbs. All mAbs were found to inhibit the binding of eCG to LH receptors except 3A3 mAb, in radioreceptor assay. Six mAbs, which were strong inhibitors of eCG binding to LH receptors and of both bioactivities, recognized the same area on the alpha subunit of eCG. All others, except 3A3, recognized epitopes close to the former, and close to each other. 3A3 mAb had a hyperstimulatory effect on FSH bioactivity, and was the only mAb that did not inhibit binding. It appeared to recognize a different epitopic area. These observations suggest that there is a main antigenic area on eCG, which corresponds to the interaction site of eCG with both receptors. It mostly involves the alpha subunit and to a lesser extent the beta subunit.

Animals↗

PubMed1993

Rapid detection of the preovulatory luteinizing hormone peak in the blue fox (Alopex lagopus) by an enzyme-linked immunosorbent assay.

An enzyme-linked immunosorbent assay (ELISA) developed for the rapid measurement of luteinizing hormone (LH) in blood of many mammalian species has been validated in the fox. For this purpose, daily plasma samples collected from six vixens during the periovulatory period were assayed for LH using ELISA. The results were compared with those obtained by radioimmunoassay (RIA), and related to parameters used to determine the time of ovulation (onset of oestrus, vaginal electrical resistance peak) and to ovarian findings. This ELISA provided a highly sensitive measure of LH (125 pg ml-1) from a 10 microliters plasma sample within 3 h. Plasma concentrations of LH measured by ELISA and RIA were significantly correlated (r = 0.911). In the blue fox, ovulation occurs once a year and coincides with the start of oestrus. The LH peak preceded the start of oestrus by 1.5 days (1-3) and preceded the vaginal electrical resistance peak by 2.2 days (1-4). The rapid and precise detection of the preovulatory LH peak by this assay provides a convenient method to determine the time of ovulation and therefore the optimum time for artificial insemination or oocyte collection for fertilization in vitro.

Animals↗

PubMed1993

Fertilization time in the bitch in relation to plasma concentration of oestradiol, progesterone and luteinizing hormone and vaginal smears.

Seven bitches of several breeds were monitored during oestrus by vaginal smears and luteinizing hormone (LH), oestradiol and progesterone plasma assays. Each bitch was inseminated into the uterus with frozen spermatozoa from seven dogs of different breeds. Each female was inseminated daily with about 200 x 10(6) motile spermatozoa. Six bitches delivered. The paternity of puppies (which indicated the fertilization time) was determined by morphological analysis. Two bitches were fertilized with one artificial insemination (AI) only and four bitches with two successive AIs. Fertilization occurred 84-180 h after the LH peak and 1-3 days before the first day of metoestrus. The gestation length, from fertilization to birth, was 58-63 days or 56-60 days after the first day of metoestrus.

Animals↗