Suppression of follicular development after chronic LHRH immunoneutralization in the ewe

McNeilly, A. S.; Jonassen, Julie A.; Fraser, H. M.

doi:10.1530/jrf.0.0760481

Cited by 153 publications

(69 citation statements)

References 28 publications

(38 reference statements)

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“…Plasma LH and FSH were measured by RIA as previously described (McNeilly et al 1976(McNeilly et al , 1986, using reagents kindly provided by Dr A Parlow (NIDDK, Torrance, CA, USA), with all samples being assayed in duplicate in the same assay. The limit of detection for NIH oLH-S18 was 0.3 ng/ml and for USDAoFSH-SIAFP-RP2 (AFP 4117A) was 0.1 ng/ml.…”

Section: Hormone Assaysmentioning

confidence: 99%

Homozygosity for a single base-pair mutation in the oocyte-specific GDF9 gene results in sterility in Thoka sheep

Nicol

Bishop²,

Pong‐Wong³

et al. 2009

Reproduction

137

116

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The control of fecundity is critical in determining mammalian offspring survival. It is regulated principally by the ovulation rate, so that primates and large farm species commonly have a single offspring. Previously, several mutations have been identified in sheep which increase the naturally low ovulation rate; although in some cases homozygous ewes are infertile. In the present study we present a detailed characterization of a novel mutation in growth differentiation factor 9 (GDF9), found in Icelandic Thoka sheep. This mutation is a single base change (A1279C) resulting in a nonconservative amino acid change (S109R) in the C-terminus of the mature GDF9 protein, which is normally expressed in oocytes at all stages of development. Genotyping all animals for which reproductive records were available confirmed this mutation to be associated with increased fecundity in heterozygous ewes and infertility in homozygotes. Analysis of homozygote ovarian morphology and a number of genes normally activated in growing follicles showed that GDF9 was not involved in oocyte activation, but in subsequent development of the follicle. This study highlights the importance of oocyte factors in regulating fertility and provides new information for structural analysis and investigation of the potentially important sites of dimerization or translational modifications required to produce biologically active GDF9. It also provides the basis for the utilization of these animals to enhance sheep production.

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Section: Hormone Assaysmentioning

confidence: 99%

Homozygosity for a single base-pair mutation in the oocyte-specific GDF9 gene results in sterility in Thoka sheep

Nicol

Bishop²,

Pong‐Wong³

et al. 2009

Reproduction

137

116

View full text Add to dashboard Cite

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“…Assays oLH was measured by RIA using the method of McNeilly et al (1985). Assay sensitivity was 0.2 ng/ml, and intraand inter-assay coefficients of variation were 5.2 and 12.1% respectively.…”

Section: Histological Studiesmentioning

confidence: 99%

Corpora lutea induced by gonadotrophin-releasing hormone treatment of anoestrous Welsh Mountain ewes: reduced sensitivity to luteinizing hormone in vivo and to chorionic gonadotrophin in vitro

Bramley

Stirling²,

Menzies³

et al. 2005

Reproduction

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Seasonally anoestrous Welsh Mountain ewes received 250 ng gonadotrophin-releasing hormone (GnRH) every 2 h, with (Group 1;n= 13) or without (Group 2;n= 14) progesterone priming for 48 h. Fourteen control ewes (Group 3) were studied during the luteal phase in the breeding season. Animals in Group 4 (n= 12) received progesterone priming followed by 250 ng GnRH at increasing frequency for 72 h, while ewes in Group 5 (n= 13) were given three bolus injections of 30 μg GnRH at 90-min intervals. All treatment regimens induced ovulation. However, only corpora lutea (CL) from ewes in Group 3 (breeding season) or Group 4 exhibited normal luteal function. Luteal luteinizing hormone (LH) receptor levels were significantly higher on day 12 than day 4, and CL from groups with adequate CL (3 and 4) had significantly higher125I-human chorionic gonadotrophin (hCG)-binding levels than the three groups with inadequate CL on day 12. LH-binding affinity was unchanged. Exogenous ovine LH (10 μg)in vivoon days 3 or 11 after ovulation induced a pulse of progesterone in ewes with adequate CL: however, ewes in Groups 1, 2 and 5 showed no significant response. Basal progesterone secretionin vitrowas significantly greater on day 4 than on day 12. Maximal steroidogenic responses of adequate and inadequate CL to hCG and to dibutyryl cyclic-3′,5′-AMP were similar at both stages of the luteal phase. However, the EC50for hCG on days 4 and 12 was 10-fold lower for groups with an adequate CL (0.1 IU hCG/ml) than for inadequate-CL groups (1 IU hCG/ml;P<0.05). Thus, in addition to the well-characterized premature sensitivity of GnRH-induced inadequate CL to endometrial luteolysin, we have shown (1) a marked decrease in total number of cells in the CL, a profound reduction in vascular surface area, and a decrease in mean large luteal cell volume (with no change in large luteal cell numbers), (2) decreased luteal LH receptor and progesterone content compared with adequate CL and (3) that CL that were becoming, or were destined to become, inadequate failed to respond to ovine LHin vivoand were 10-fold less sensitive to hCG in terms of luteal progesterone secretionin vitro.

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“…(32). The sensitivity of the assay (90% B/Bo) was 0.2 to 0.4 pg NIH-LH-S18/1 plasma (NIDDK, Bethesda, MD, USA) and the mean intra-and interassay coefficients of variation were 12.1% and 13.1%, respectively based on high, medium, and low quality control plasma samples run in a total of I2 assays.…”

Section: Ria\mentioning

confidence: 99%

Luteinizing Hormone Responses to N‐Methyl‐D,L‐Aspartate During a Photoperiodically‐lnduced Reproductive Cycle in the Ram

Lincoln

1991

J Neuroendocrinology

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Aspartate and glutamate represent a major class of excitatory amino-acid neurotransmitters in the vertebrate brain, and stimulation of glutaminergic receptors by the specific agonist N-methyl-D,L-aspartate (NMDA) induces luteinizing hormone-releasing hormone (LHRH) and LH secretion. In this study, we used NMDA as a probe to investigate the hypothalamic regulation of LH secretion at different stages of a reproductive cycle in Soay rams induced by exposure to alternating 16-week periods of long and short days. NMDA (20 mg/kg) injected intravenously caused an acute increase in blood plasma concentrations of LH, with a significant increase within 2 to 4 min, and peak levels within 20 min. The magnitude of the response changed markedly during the cycle; it was greatest in the sexually inactive phase under long days (with a linear dose-response over the range 1 to 20 mgikg NMDA) and least in the sexually active phase under short days (only 20 mg/kg NMDA produced a small response). Pituitary responsiveness to a standard dose of LHRH (5.3 ng/kg iv) varied only slightly at the different stages and could not account for the observed changes in the LH response to NMDA. There were the expected changes in the endogenous pattern of LH secretion during the cycle, with high frequency LH pulses occurring during the sexually active phase. There was an inverse relationship between the frequency of LH pulses and the LH response to NMDA. Pretreatment of rams with an LHRH antagonist (36 pg/kg iv; Syntex, RS18286) totally blocked the LH response to both NMDA and LHRH, while in a separate study, treatment with dexamethasone (synthetic glucocorticoid, 133.4 pglkg iv) partially blocked the LH responses. The overall results indicate that NMDA stimulates LHRH secretion in the ram and the response is independent of the activation of the hypothalamo-pituitary-adrenal axis. The variation in the LH response during the reproductive cycle may reflect changes in the releasable stores of LHRH in the median eminence. These appear to be depleted in the sexually active phase, when LHRH is secreted in pulses at high frequency. The variation in the response to NMDA may also reflect changes in release of endogenous excitatory amino-acids, which act via NMDA receptors to form part of the physiological regulation of the reproductive cycle in the ram.The dicarboxylic amino-acids aspartate and glutamate represent a major class of excitatory neurotransmitters in the vertebrate brain ( I ) . These amino-acids have excitatory effects through at least three classes of receptors of which the N-methyl-D,Laspartate (NMDA) receptor class is best characterized, and these receptors are apparently involved in the neural control of reproduction (2). Studies in the rat have shown that the administration of NMDA causes the release of luteinizing hormone (LH) from the anterior pituitary gland by inducing the secretion of LHreleasing hormone (LHRH) from the hypothalamus (3, 4), and there is evidence that both NMDA and non-NMDA excitatory amino-acid receptors are in...

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Suppression of follicular development after chronic LHRH immunoneutralization in the ewe

Cited by 153 publications

References 28 publications

Homozygosity for a single base-pair mutation in the oocyte-specific GDF9 gene results in sterility in Thoka sheep

Homozygosity for a single base-pair mutation in the oocyte-specific GDF9 gene results in sterility in Thoka sheep

Corpora lutea induced by gonadotrophin-releasing hormone treatment of anoestrous Welsh Mountain ewes: reduced sensitivity to luteinizing hormone in vivo and to chorionic gonadotrophin in vitro

Luteinizing Hormone Responses to N‐Methyl‐D,L‐Aspartate During a Photoperiodically‐lnduced Reproductive Cycle in the Ram

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