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See detailContribution à l’étude de l’utilisation répétée de la gonadotrophine chorionique équine (eCG) dans le contrôle de la reproduction
Drion, Pierre ULg

Doctoral thesis (2001)

Various molecules including steroids, prostaglandins, peptides and glycoproteins are largely used in reproduction programs in domestic mammals. Treatments including pituitary gonadotrophins (Follitropin ... [more ▼]

Various molecules including steroids, prostaglandins, peptides and glycoproteins are largely used in reproduction programs in domestic mammals. Treatments including pituitary gonadotrophins (Follitropin —FSH-, Lutropin —LH-, human menopausal Gonadotrophin —hMG-) and placental gonadotrophins (human Chorionic Gonadotrophin —hCG-, equine Chorionic Gonadotrophin —eCG- also called Pregnant mare serum gonadotrophin —PMSG-) are used for a long time to treat infertility or as a way to better control the reproductive cycles of cattle, horses, goats, sheep, dogs, pigs and more recently rabbits, monkeys and humans. The literature concerning the administration of gonadotrophins in different species than source species reports data’s on active immunization and suggests that repeated administration of these hormones lead to induction of antibodies. In this aim, we realized experimental investigations in different ruminant species in order to get objective informations and experimental observations on possible side effects of repeated xenogenic gonadotrophic treatments as circulating antibodies in plasma and decreased response to repeated administration. In this aim, we recorded reproductive performances in parallel with measurement of circulating antibodies in plasma using an in vitro radiometric method. So, ninety-eight goats of two herds were followed over 4 years in a program of annual artificial insemination after estrus induction/synchronization, including progestagen administration (vaginal sponge) followed by prostaglandin analog and equine chorionic gonadotrophin (eCG) 48h before sponge removal. After withdrawal of progestagen, goats were sampled every 4 hours for determination of LH surge and tested for estrus by the presence of a buck. Seven days after AI, endoscopic examination of the ovaries was performed while plasma progesterone was used at day 21-22 after AI for early pregnancy diagnosis. Finally, echography was performed at day 40-45, before monitoring parturition, number and sex of kids. All the goats were sampled before and after each treatment, for anti-eCG antibodies screening. Statistical analysis of the results clearly established a significant effect of the treatments on anti-eCG antibodies while no effect of the herd or of the age of the female. A significant difference was found between the two herds when the delay for coming out of estrus or for LH surge was considered. The antibodies significantly influenced the time of coming out of estrus as well as the time of LH surge. No influence of the age at the first treatment on the time of estrus or the time of LH surge was found. The antibodies after treatment significantly influenced the percentage of ovulating females as well as kidding rate, whatever the age of the female. Finally, no effect of antibodies on prolificacy was found even if antibodies significantly influenced the fertility. In the following experimental protocol, we verified the possible effect of high frequency of administration on the immune response to eCG. The profiles of eCG binding rate, in the blood of cows submitted weekly for 5 to 10 weeks to repeated high doses (1000-2000 IU) of equine chorionic gonadotrophin in an ovum pick up experimental protocol were followed. The profiles clearly indicated a marked increase of eCG binding rate after 3 to 5 injections of the exogenous hormone to the females. The statistical analysis of the results established that treatments induced a significant increase in binding rates after 6 and 3 injections according to the group. These binding rates remained elevated for at least 1 week following the last injection and decreased afterwards. The values of plasma binding rates following repeated eCG administration differed significantly between groups and from one cow to another with some cows presenting no significant immune response while others were more reactive against the hormone. Finally, the experiment on sheep consisted in the estimation of the long-term consequences on reproduction performance, of the oestrus synchronization treatments that are annually applied to ewes. In this aim, nine dairy flocks were followed. An hormonal treatment combining the insertion of a vaginal fluoro-gestone acetate (FGA) sponge for 14 days and the injection of about 500 IU of pregnant mare serum gonadotropin (PMSG) at withdrawal was applied to the ewes in seven of the nine flocks. Females of the two other flocks were used as controls. Blood samples were taken from each female just before the treatment (to test for the presence of residual antibodies) and 20 days after the PMSG injection. Anti-PMSG antibody binding rates were calculated for each blood sample. The residual binding rate increased with age and induce negative effects on the following years reproduction performances, i.e., they increased the probability that the ewes would not become pregnant. [less ▲]

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See detailCaractéristiques de la reproduction dans l’espèce caprine
Zarrouk, A.; Souilem, O.; Drion, Pierre ULg et al

in Annales de Médecine Vétérinaire (2001), 145

This review pointed out the physiological basis of goat reproduction. So far assimilated to ewes, goats presented their own characteristics concerning the sexual activity and the endocrinology of ... [more ▼]

This review pointed out the physiological basis of goat reproduction. So far assimilated to ewes, goats presented their own characteristics concerning the sexual activity and the endocrinology of pregnancy. The well understanding of goat particularities is essential to control cyclic activities and reproduction applicationCe travail passe en revue les bases physiologiques de la reproduction dans l’espèce caprine. Longtemps assimilée à la brebis, la chèvre présente des spécificités propres, tant sur le plan du déroulement des cycles sexuels que sur le plan de l’endocrinologie de la gestation. Une bonne connaissance des particularités de la reproduction dans cette espèce permet une meilleure maîtrise du contrôle du cycle sexuel et des techniques de la reproduction [less ▲]

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See detailIncrease of Plasma Ecg Binding Rate after Administration of Repeated High Dose of Ecg to Cows
Drion, Pierre ULg; De Roover, R.; Houtain, J. Y. et al

in Reproduction Nutrition Development (2001), 41(3), 207-215

Equine chorionic gonadotrophin (eCG) is still used to promote follicular growth in cattle and, more recently with an increased frequency of administration, in ovum pick-up protocols. The aim of this ... [more ▼]

Equine chorionic gonadotrophin (eCG) is still used to promote follicular growth in cattle and, more recently with an increased frequency of administration, in ovum pick-up protocols. The aim of this experiment was to verify the possible effect of high frequency of administration on the immune response to eCG. The profiles of eCG binding rate, in the blood of two groups (A, B) of 4 primiparous cross breed beef cows (3-3.5 years old) submitted weekly for 5 to 10 weeks to repeated high doses (1000-2000 IU) of equine chorionic gonadotrophin, are presented in this paper. A sensitive radiometric method was used to detect antibodies in plasma. The profiles clearly indicated a marked increase of eCG binding rate after 3 to 5 injections of the exogenous hormone to the females. The statistical analysis of the results established that treatments induced a significant increase (P < 0.01) in binding rates after 6 and 3 injections in group A and B respectively. These binding rates remained elevated for at least 1 week following the last injection and decreased afterwards. The values of plasma binding rates following repeated eCG administration differed significantly between groups (0.90+/-1.04 and 1.04+/-0.11 for groups A and B before treatment versus 11.77+/-0.92, 6.70+/-0.85 for groups A and B after treatment, P < 0.01) and from one cow to another (P < 0.01) with some cows presenting no significant immune response while others were more reactive against the hormone (at least 3 injections). [less ▲]

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See detailFour years of induction/synchronization of estrus in dairy goats: effect on the evolution of eCG binding rate in relation with the parameters of reproduction
Drion, Pierre ULg; Furtoss, V.; Baril, G. et al

in Reproduction Nutrition Development (2001), 41(5), 401-412

Ninety-eight Alpine goats of two herds were followed over 4 years in a program of annual artificial insemination after estrus induction/synchronization, including progestagen administration (vaginal ... [more ▼]

Ninety-eight Alpine goats of two herds were followed over 4 years in a program of annual artificial insemination after estrus induction/synchronization, including progestagen administration (vaginal sponge) followed by prostaglandin analog and equine chorionic gonadotrophin (eCG) 48 h before sponge removal. Goats were sampled every 4 hours from the 16th to the 56th following sponge removal, for determination of LH surge and tested for estrus by the presence of a buck. Seven days after AI, endoscopic examination of the ovaries was performed to determine the number of corpus lutea. Pregnancy diagnosis was performed at day 21-22 post AI by determination of plasma progesterone and at day 40-45 by ultrasonography. Parturition, number and sex of kids were recorded. All the goats were sampled before and after each treatment, for anti-eCG antibodies screening. Statistical analysis of the results clearly established a significant effect of the treatments on anti-eCG antibodies. Time of estrus and LH surge were significantly different between herd. The antibodies significantly delayed the time of coming out of estrus as well as the time of LH surge. Two antagonistic effects were evidenced: first, the delayed of time of estrus and time of LH surge in relation with the immune reaction to eCG; secondly, the ahead of time of estrus and time of LH surge during the years of treatment, identical to both herd. The antibodies negatively influenced the percentage of ovulating females as well as kidding rate. Finally, no effect of antibodies on prolificacy was found. [less ▲]

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See detailDoes annual repetition of estrous induction influence the fertility of goats after A.I. at a fixed time ?
Drion, Pierre ULg; Furstoss, V.; Baril, G. et al

in Biotechnologie, Agronomie, Société et Environnement = Biotechnology, Agronomy, Society and Environment [=BASE] (2001), 5(1), 28-29

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See detailLe développement folliculaire chez la vache. 2. Mécanismes hormonaux au cours du cycle et du postpartum.
Drion, Pierre ULg; Beckers, Jean-François ULg; Derkenne, F. et al

in Annales de Médecine Vétérinaire (2000), 144

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See detailMise au point relative à la croissance folliculaire chez la vache.1. Aspects morphologiques et cinétiques
Hanzen, Christian ULg; Lourtie, O.; Derkenne, F. et al

in Annales de Médecine Vétérinaire (2000), 144

La mise en place du potentiel folliculaire se fait bien avant la naissance chez les mammifères. Le nombre maximal de cellules gamétiques contenues dans l'ovaire est atteint après une première phase de ... [more ▼]

La mise en place du potentiel folliculaire se fait bien avant la naissance chez les mammifères. Le nombre maximal de cellules gamétiques contenues dans l'ovaire est atteint après une première phase de multiplication aux environs du centième jour de gestation chez la vache et décroît progressivement ensuite jusqu'à la naissance. A cette première phase succède une phase de croissance et une phase de maturation, cette dernière concernant surtout l'ovocyte. Cette évolution ne concerne qu'un nombre réduit de follicules, la plupart d'entre eux subissant l'atrésie. La croissance folliculaire présente deux caractéristiques. Elle se manifeste sous la forme de croissances et de régressions successives de plusieurs follicules appelées vagues. Chacune d'entre elles consiste en l'émergence, tous les 7 à 9 jours environ, de plusieurs follicules de diamètre égal ou supérieur à 5 mm parmi lesquels apparaîtra le follicule dominant. Ces vagues ont été décrites au cours du cycle, pendant la puberté, le postpartum et la gestation. Par ailleurs, il est bien connu que parmi les follicules recrutés, c'est à dire dont la croissance s'est poursuivie au-delà d'une taille à laquelle ils subissent habituellement l'atrésie, un nombre limité, caractéristique de l'espèce, va être sélectionné pour arriver éventuellement au stade ovulatoire. Ceux-ci vont à ce moment exercer une dominance tout à la fois fonctionnelle et morphologique sur les autres follicules. [less ▲]

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See detailLa pseudogestation chez la chèvre, facteur d'infertilité
Zarrouk, Anissa; Drion, Pierre ULg; Beckers, Jean-François ULg

in Annales de Médecine Vétérinaire (2000), 144

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See detailLivre Substances hormonales. Partim Hormones. Médicaments du système hormonal – hormones sexuelles et autres médicaments du système reproducteur
Drion, Pierre ULg

in Répertoire commenté des Médicaments à Usage vétérinaire (2000)

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See detailFrom the germinal cells to the newborn animal: the transmission of genes and life through the generations
Drion, Pierre ULg; Scenzi, Otto; Ectors Francis et al

(1999, May)

During the last decade, the technology of reproduction progressed considerably leading to a certain availability of in vitro methods for fertilization, maturation of the oocyte and culture system for the ... [more ▼]

During the last decade, the technology of reproduction progressed considerably leading to a certain availability of in vitro methods for fertilization, maturation of the oocyte and culture system for the embryos. The most spectacular manipulations are cloning and transgenesis… This review focuses on the early appearance of the germinal cells precursors and the longstanding destiny of the gametes in mammals. The evident complexity and long-term programmation of events in gametes and early embryo explain the difficulties to succeed in in-vitro methods and the occurrence of unexpected alterations of development, e.g. embryonic or fetal mortalities, large weight newborn syndrome and other dys-regulations in imprinting or DNA transmission. “Studying and teaching the reproductive physiology in mammals, we sometimes imagine that a newborn animal survived two pregnancies: the first one would be a high risk pregnancy that represents the oocyte development and survival inside the follicle with a tetraploïd genome and the zona pellucida & cumulus cells as placenta-like structures. Around the first birth (ovulation), oocytes (individuals) accept in vitro conditions for maturation, fertilization and culture. Afterwards, a second pregnancy will be necessary in the mother or in the recipient uterus; a low risk pregnancy depending on the oocyte competence acquisition and on the conditions or length of exposure in vitro. “ [less ▲]

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See detailPregnancy Associated Glycoproteins in Ruminants: Inactive Members of the Aspartic Proteinase Family
Beckers, Jean-François ULg; Drion, Pierre ULg; Garbayo, J. M. et al

in Acta Veterinaria Hungarica (1999), 47(4), 461-9

The Pregnancy Associated Glycoproteins (PAGs) presented in this paper are largely expressed in the ruminant placenta. These proteins are classified as probably inactive members of the aspartic proteinase ... [more ▼]

The Pregnancy Associated Glycoproteins (PAGs) presented in this paper are largely expressed in the ruminant placenta. These proteins are classified as probably inactive members of the aspartic proteinase family. Pepsinogen, renin, cathepsin E [less ▲]

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See detailLa mortalité embryonnaire. 2. Implications hormonales
Hanzen, Christian ULg; Lourtie, O.; Drion, Pierre ULg et al

in Annales de Médecine Vétérinaire (1999), 143

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See detailLa mortalité embryonnaire. 1. Aspects cliniques et facteurs étiologiques dans l'espèce bovine
Hanzen, Christian ULg; Drion, Pierre ULg; Lourtie, O. et al

in Annales de Médecine Vétérinaire (1999), 143

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See detailPMSG et production d'anticorps : relation avec la productivité des lapines
Theau-Clément, M.; Lebas, F.; Drion, Pierre ULg et al

in Cuniculture (1999), 26(3), 123-126

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See detailPregnancy-associated glycoproteins in the ruminants: inactive members of the Aspartic Protease family
Beckers, Jean-François ULg; Drion, Pierre ULg; Garbayo, J. M. et al

in Proceedings of the Middel European Buiatrics Congress, 1998 (1998, May 21)

Proteins secreted by the placenta, when detected in the peripheral circulation of the mother, can be useful indicators of both pregnancy and feto-trophoblast well-being (1-3). In 1982, Butler et al. (4 ... [more ▼]

Proteins secreted by the placenta, when detected in the peripheral circulation of the mother, can be useful indicators of both pregnancy and feto-trophoblast well-being (1-3). In 1982, Butler et al. (4) isolated two pregnancy-specific proteins (PSPA and PSPB) from bovine placental membranes. PSPA was identified as a-fetoprotein which is not strictly limited to pregnancy, while PSPB was confirmed as placenta’s and pregnancy’s specific (5). PSPB was characterized as a glycoprotein showing relative molecular masses (Mr) between 47 and 53 kDa and presenting different isoelectric points (from 4.0 to 4.4). The Mr of PSPB was similar to the Mr of the molecule isolated by Laster in 1977 (6). In 1991, Zoli et al. (7) purified a pregnancy-associated glycoprotein (PAG), later designated PAG_1 and presently designated as PAG_I_ 67 considering its Mr. When isolated from bovine fetal cotyledons PAG_I_67 was an acidic glycoprotein of 67 kDA. Four isoforms (PI : 4.4, 4.6, 5.2 and 5.4) were detected in the initial preparation. Later molecular cloning studies showed that the PSPB and PAG_I_67 were closely related in primary structure (8). These glycoproteins (either PSPB and PAG_I_67) could be detected in the maternal circulation at around the time that the trophoblast formed definitive attachment to the uterine wall (figures A & B). Concentrations increased gradually therefore and reached peak values just before parturition at about 1 to 5 mg/ml (9).The PSPB and PAG molecules are routinely determined in peripheral maternal blood as pregnancy markers in cattle (5, 9,10). Glycoproteins immunologically related to PAG_I_67 and PSPB have been isolated and partially characterized from ovine fetal cotyledons: oPAG later designated oPAG_I (11) and oPSPB (12). They also have been detected in maternal blood by week third (12) or fourth (13) after breeding. Different forms (differing in Mr and isoelectric point) were characterized after isolation from sheep cotyledons cultured in vitro (14). Very recently, 3 different PAGs were characterized from goat placenta having Mr of 55, 59 and 62 kDa. Each of them presented various isoeletric points (15). In 1991, Xie et al., cloned PAG (now known as PAG_I_67) from late bovine and ovine placenta by screening cDNA libraries with two anti-PAG antisera (16). The bovine and ovine cDNAs encoding PAG_I shared 86% nucleotide sequence identic with one and other and encoded proteins of 380 and 382 aminoacids respectively including a 15 aminoacid signal sequence. However, protein sequence data, (peptidic sequencing) already showed the first aminoacid of the bovine PAG_I_67 was an arginine that corresponded to another one located at position 39, downstream of the side of signal sequence cleavage, indicating that PAG_I_67 undergoes post-translational modifications from a proform. [less ▲]

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See detailEndocrinologie de la gestation chez les ruminants: les protéines placentaires
Zarrouk, Anissa; Remy, Benoît ULg; Sulon, Joseph ULg et al

in Annales de Médecine Vétérinaire (1998), 142

The two main groups of placental proteins of ruminants are related in this paper: Placental lactogens and Pregnancy-Specific (-Associated) Proteins. Placental lactogens belong to the prolactin and growth ... [more ▼]

The two main groups of placental proteins of ruminants are related in this paper: Placental lactogens and Pregnancy-Specific (-Associated) Proteins. Placental lactogens belong to the prolactin and growth hormone family. They stimulate mammogenesis, fetal growth hormone family. They stimulate mammogenesis, fetal growth and maternal metabolism. Pregnancy-Specific proteins and Pregnancy-Associated glycoproteins belong to the aspartic proteinase family as pepsine, cathepsine D, E. These two groups of proteins are secreted in the maternal circulation by the binucleate cells after their migration to and fusion with the uterine cells. Their profiles were determined through RIA. Further investigations are in progress to rely secretory profiles with alterations of the trophoblastic function as occuring in embryonic mortality, abortion, fetal distress... [less ▲]

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See detailEffets de la répétition des traitements Progestagènes/PMSG chez la chèvre
Baril, G.; Leboeuf, B.; Remy, Benoit et al

(1998, April 30)

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See detailUtilisation répétée des gonadotropines exogènes dans le contrôle de la reproduction: justifications et effets secondaires potentiels
Drion, Pierre ULg; Houtain, Jean-Yves; MC Namara, M. et al

in Annales de Médecine Vétérinaire (1998), 142(2), 373-396

Gonadotropins of pituitary origin (follitropin -FSH-, lutropin -LH-, human menopausal gonadotropin -hMG) or trophoblastic origin (human chorionic gonadotropin - hCG- also called pregnant urine ... [more ▼]

Gonadotropins of pituitary origin (follitropin -FSH-, lutropin -LH-, human menopausal gonadotropin -hMG) or trophoblastic origin (human chorionic gonadotropin - hCG- also called pregnant urine gonadotropin -pU-, equine chorionic gonadotropin -eCG- also called pregnant mare serum gonadotropin -PMSG-) are largely used to treat infertility or to better control sexuality in various species of mammals: bovine, canine, caprine, equine, feline, human,ovine, porcine, rabbit, ... This manuscript reports the discovery of these molecules, describes their biochemical characteristics and gives the main indications (e.g. oestrus induction and synchronization, ovulation, superovulation, fertility improvement, anoestrus treatment, receptivity induction) in animals and human. Litterature data reporting on effects and possible side effects of their repeated use are presented. Due to slight differences in amino acids sequences, carbohydrates contents and tridimentionnal structures, repeated use of exogeneous gonadotropins may induce immunological reactions leading to non specific reactions and lower biological response. A reflection concludes this revue, pointing out the positive influence of the philogenetic distance existing between the species origin of the gonadotropin (human or equine) and the treated one, on the intensity of the immune reaction. [less ▲]

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