J L Juengel

AgResearch, Hamilton City, Waikato, New Zealand

Are you J L Juengel?

Claim your profile

Publications (101)367.59 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Ewes attaining puberty in their first year perform better at 2 years of age.•Selection of replacement ewes on this basis may be beneficial for flock performance.•The proportion of ewe lambs attaining puberty each year was highly variable.•This variability was not entirely explained by differences in live weight.
    Small Ruminant Research 11/2014; · 1.12 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Experiments were designed to investigate the effect of different doses and timing of an eCG treatment given during GnRH-based synchronization protocols on follicular dynamics and fertility in cattle. In Exp. 1, Angus heifers (n = 50) received a 7-d Ovsynch + progesterone protocol (on d 0, GnRH and progesterone insert were administered; on d 7, progesterone insert was removed and PGF2α was injected; and on d 9.5, GnRH was injected 56 h after progesterone removal) with eCG (0, 300, 500, 700, or 1,000 IU) administered on d 7. In Exp. 2, Angus cows (n = 27) received the same protocol as Exp. 1 and were assigned randomly to receive 0 or 400 IU eCG i.m. on d 2 or 7. In Exp. 3, Angus cows (n = 18) received a 6-d Ovsynch + progesterone protocol and were randomly assigned to receive 0 or 800 IU eCG on d 3 of the protocol (Exp. 3a). A pilot field trial was also performed using the same treatments in suckled Angus-cross cows (n = 72; Exp. 3b). In Exp. 4, beef heifers (n = 200) were assigned randomly to the same treatments as in Exp. 3, but the second GnRH was not given, with Holstein bulls introduced on d 6. In Exp. 5, Angus cows (n = 12) received the same treatment as in Exp. 3, but were not inseminated. Progesterone concentrations were assessed in plasma collected during the estrous cycle following synchronization. Ultrasonography was used to monitor ovarian dynamics and to diagnose pregnancy. In Exp. 1, the mean number of ovulations was affected (P < 0.02) by the dose of eCG and the stage of follicular development when administered. Treatment with eCG on d 2 tended (P < 0.08) to extend the interval from PGF2α to ovulation, but was not successful in inducing double ovulations. In contrast, eCG on d 3 increased (P < 0.01) the number of cows with double ovulation when administered i.m. and increased (P < 0.04) pregnancy rate in single ovulating heifers after bull breeding (68.0 vs. 53.1%). This treatment also elevated progesterone concentrations during the estrous cycle following synchronization. Thus, the mechanism by which administration of eCG on d 3 of the synchronization increased pregnancy rates may be through supporting development of a healthy follicle and subsequent corpus luteum capable of secreting increased concentrations of progesterone during early pregnancy. In conclusion, strategic administration of eCG during a synchronization protocol can be used to improve reproductive performance through increased pregnancy rates in single ovulating animals as well as the induction of twin ovulations for twinning.
    Journal of animal science. 11/2014; 92(11):4935-48.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) act synergistically to regulate granulosa cell proliferation and steroid production in several species. Several non-Sma and mothers against decapentaplegic (SMAD) signalling pathways are involved in the action of murine and ovine GDF9 and BMP15 in combination, with the pathways utilised differing between the two species. The aims of this research were to determine if human GDF9 and BMP15 also act in a synergistic manner to stimulate granulosa cell proliferation and to identify which non-SMAD signalling pathways are activated. Human GDF9 with BMP15 (GDF9 þ BMP15) stimulated an increase in 3 H-thymidine incorporation (P , 0.001), which was greater than the increase with BMP15 alone, while GDF9 alone had no effect. The stimulation of 3 H-thymidine incorporation by GDF9 þ BMP15 was reduced by the addition of inhibitors to the SMAD2/3, nuclear factor-K B (NF-K B) and c-Jun N-terminal kinase (JNK) signalling pathways. Inhibitors to the SMAD1/5/8, extracellular signal-regulated kinase mitogen-activated protein kinase (ERK-MAPK) or p38-MAPK pathways had no effect. The addition of the BMP receptor 2 (BMPR2) extracellular domain also inhibited stimulation of 3 H-thymidine incorporation by GDF9 þ BMP15. In conclusion, human GDF9 and BMP15 act synergistically to stimulate granulosa cell proliferation, a response that also involves species-specific non-SMAD signalling pathways.
    Reproduction Fertility and Development 08/2014; · 2.58 Impact Factor
  • Reproduction Fertility and Development 02/2014; · 2.58 Impact Factor
  • Reproduction Fertility and Development 01/2014; · 2.58 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Attainment of puberty is a key developmental event influenced by genetic and environmental factors. In examining age of attainment of puberty, we observed closely related rams from the Davisdale line whose daughters differed in age at which they attained puberty. A candidate gene approach was used to identify mutations that may underlie these observed differences. Four rams with divergent phenotypes for their daughter's age at onset of puberty were selected for whole genome sequencing. The coding regions of genes with known roles in regulating reproductive function were searched for single nucleotide polymorphisms (SNPs) that altered the amino acid sequence of the protein. Of interest were 3 SNPs in the leptin receptor (LEPR) gene. A Sequenom assay was developed to determine the genotype of these SNPs in daughters of 17 sons of a founding sire. A higher percentage of ewe lambs homozygous for the LEPR mutations failed to undergo puberty prior to 1 year of age, and those that did undergo puberty during the first breeding season on average were 18 days older than homozygous wild-type ewes. Heterozygous ewes were intermediate for both measurements. Given the predicted change in protein function produced by the mutation in LEPR and the strong associations between the genotype and onset of puberty phenotypes, we propose that this mutation in LEPR underlies the observed difference in age at onset of puberty in the Davisdale line. Furthermore, these animals will likely provide a useful model to better understand the role of leptin in regulation of puberty.
    Biology of Reproduction 01/2014; · 4.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Partial neutralization of bone morphogenetic protein 15 (BMP15) bioactivity by immunization is known to increase ovulation rate in sheep. However, it remains uncertain whether BMP15 vaccination would be a suitable procedure for increasing lambing rate. The aim of this study was to compare the efficacy of a BMP15 vaccination treatment on lamb production to that of commercially-available androstenedione-based vaccines that are used for this purpose. Ewes were immunized for 3 yr against androstenedione, BMP15, or no antigen (control). Vaccination with androstenedione or BMP15 altered (P < 0.05) ovulation rate as well as litter size at mid-pregnancy, birth, and weaning compared to controls. No differences were detected in the proportions of ewes conceiving in the first cycle or partial failure of multiple ovulations. Both gender and litter size affected birth weight of the lamb (P < 0.05), but no effect of treatment was found. Growth rate was significantly affected (P < 0.05) by gender, birth weight, and the number of lambs raised, but not treatment. In conclusion, immunization against either androstenedione or BMP15 increased ovulation rate. Androstenedione vaccination also increased the number of lambs weaned (P < 0.05). Bone morphogenetic protein 15 vaccination altered the pattern of the number of lambs weaned, but no increase in lamb production was observed as more ewes produced zero or three lambs. Overall, androstenedione or BMP15 vaccination did not significantly affect embryo/fetal survival or lamb performance independently of the effects of these treatments on ovulation rate.
    Journal of Animal Science 10/2013; · 2.09 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The goal was to estimate the heritabilities and genetic variances for embryo/fetal survival (ES) in sheep along with the effect of premating ewe weight, age and bilateral/unilateral ovulation on ES. The data consisted of 11,369 records on ovulation rate and litter size. Statistical models for ES included year and ovulation rate as fixed effects, premating ewe weight and age as covariates, and sire of embryo, maternal grandsire (MGS) and permanent maternal environmental effects of the ewe as random effects. The variance components were estimated using REML. In ewes that survived to year 6, the mean litter size was 1.87, 2.05, 2.01, 2.07, and 1.91 ± 0.04 in ewes of age 2, 3, 4, 5, and 6 respectively. Litter size was less in ewes of age 2 and 6 compared to ewes of age 3, 4, and 5 (P < 0.01). Ovulation rate was lower at age 2 and increased from age 2 to 6 (P < 0.05). Two year old ewes had lower ES than 3 year old ewes (P < 0.01) and the probability of ES decreased after age 3 (P < 0.01). Thus, ES contributes significantly to lower fertility in two year old ewes. In ewes with high ovulation rates (i.e., 5 corpora lutea (CL)), more balanced ovulations (i.e., 2 or 3 CL on each ovary) tended (P = 0.06) to be associated with increased ES. A quadratic relationship was observed between ewe weight and litter size (P < 0.01) and a positive linear relationship between premating ewe weight and ovulation rate (P < 0.01). A quadratic effect of ewe weight on ES was observed, with decreased ES for low and high ewe weights (P < 0.01). The optimal ewe weight for ES increased with ovulation rate, which is consistent with the requirement of greater body reserves for maintaining a larger number of fetuses during gestation. A quadratic relationship between ewe weight and the probability that a ewe is able to maintain a pregnancy was also observed (P < 0.05). Pregnancy loss is due to failure of the embryo/fetus or failure of the dam to maintain the pregnancy. The sire of the embryo only influences the embryo whereas the MGS influences both the ewe and the embryo. The heritability for the direct additive effect on ES in ewes that lambed was 0.0081 ± 0.0139 and the heritability for the maternal additive effect was 0.0447 ± 0.0242. The permanent maternal environmental variance component was significant and explained 8.5% of the phenotypic variance. Thus, genetically, the dam's ability to maintain a pregnancy has 5.5 times the effect on pregnancy loss than the embryo's ability to survive, and this in turn was only half the size of the permanent environmental effect. Therefore, selection among dams based on the mean embryonic survival of their embryos will provide an effective way to improve embryonic survival.
    Journal of Animal Science 08/2013; · 2.09 Impact Factor
  • Jennifer L Juengel, George H Davis, Kenneth McNatty
    [Show abstract] [Hide abstract]
    ABSTRACT: Livestock populations have been subjected to strong selection pressure to improve reproductive success and this has led to the identification of lines of animals with increased fecundity. These animals provide a rich biological resource for discovery of genes and regulatory mechanisms that underpin improved reproductive success. To date, three genes, all related to the transforming growth factor beta (TGFB) pathway, have been identified as having mutations that lead to alterations in ovulation in sheep. In addition, several other lines of sheep have been identified with putative mutations in single genes with major effects on ovulation rate. This review is focused on the identification of the mutations affecting ovulation rate and how these discoveries have provided new insights into control of ovarian function.
    Reproduction 06/2013; · 3.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Fibroblast growth factors (FGFs) modulate ovarian function, including FGF8 and FGF18. These FGFs activate the same receptors, although FGF18 is unusual in that it increases apoptosis in ovarian granulosa cells whereas the 'typical' response to FGF is increased proliferation. The objective of the present study was to determine which early response genes and pathways are activated by FGF8 and FGF18 in bovine granulosa cells. FGF8 increased abundance of mRNA encoding the FGF-responsive genes SPRY1, SPRY2, SPRY4, NR4A1 and NR4A3 whereas FGF18 did not. FGF8 increased but FGF18 decreased levels of mRNA encoding the growth arrest associated protein, GADD45B. FGF8 increased ERK1/2 phosphorylation but FGF18 did not. Microarray analysis identified EGR1, FOS, FOSL1, BAMBI, XIRP1 and PLK2 as other FGF8 immediate-early response genes, and FGF18 stimulated EGR1, FOSL1, BAMBI and PLK2, but not FOS or XIRP1. This study demonstrates that FGF8 and FGF18 signal through divergent pathways in ovarian granulosa cells, despite reportedly similar receptor activation patterns.
    Molecular and Cellular Endocrinology 05/2013; · 4.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Improved livestock production efficiency through greater embryonic survival (ES) is of economic and animal welfare benefit. Physiological characterization of animals that are extreme outliers for ES provides a valuable opportunity to identify a naturally occurring mechanism by which this trait may be enhanced. The objective was to determine the likely cause for the lifetime history of enhanced or reduced ES in a line of ewes selected for high fecundity. To address this question, progesterone concentrations in peripheral plasma as well as ovarian and uterine venous plasma samples were compared between groups of ewes with a lifetime history of either enhanced or reduced ES. The ability of the uterus to synthesize progesterone de novo at Day 5 of gestation was also tested. Ewes with enhanced ES had an earlier rise in progesterone concentration after estrus, irrespective of pregnancy status. In addition, there were increased concentrations of progesterone in the uterine vein in enhanced ES compared with reduced ES ewes on Day 5 of gestation (8.3 ± 0.8 ng/mL and 3.9 ± 1.4 ng/mL, respectively, P < 0.05). However, there were no differences in ovarian venous plasma (enhanced ES, 1725 ± 166 ng/mL; reduced ES, 1665 ± 268 ng/mL) at Day 5 of gestation. Although the endometrial tissue of some ewes (3/8) at Day 5 of gestation expressed three of the key genes necessary for regulation of de novo synthesis of progesterone, expression was not present exclusively in either of the two ES groups and therefore was unlikely to explain differences in the uterine vein progesterone concentrations between the enhanced and reduced ES groups. Collectively, the earlier rise in progesterone concentrations in peripheral plasma during the first week of gestation in the enhanced ES animals was independent of the presence of an embryo. Moreover, increased progesterone concentrations were also observed in the uterine vein at Day 5 of gestation of the enhanced ES ewes. It is proposed that the difference in uterine vein progesterone concentration was likely due to the differences in ovarian venous blood supply rather than de novo synthesis by the uterus.
    Theriogenology 05/2013; · 2.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aims were to investigate whether oocyte-secreted growth factors from a high (i.e. rat) and low (i.e. sheep) ovulation-rate species could stimulate 3H-thymidine incorporation in granulosa cells (GC) from antral follicles from the same or across species. Denuded oocytes (DO) were co-incubated with GC with or without specific antibodies to growth differentiating factor 9 (GDF9) or bone morphogenetic protein 15 (BMP15). Co-incubations of DO-GC from the same or across species significantly increased thymidine incorporation in GC with increasing numbers of DO. GDF9 immuno-neutralisation reduced thymidine incorporation in rat GC co-incubated with either rat or ovine DO and in ovine GC co-incubated with ovine or rat DO. BMP15 immuno-neutralisation only reduced thymidine incorporation when ovine DO were co-incubated with either ovine or rat GC. Western blotting of oocytes co-incubated with GC identified GDF9 and BMP15 proteins for sheep, and GDF9 protein for rats in oocyte lysates and incubation media. With respect to rat BMP15, a promature protein was identified in the oocyte lysate but not in media. Expression levels of GDF9 relative to BMP15 mRNA in DO co-incubated with GC were highly correlated (R2=0.99) within both species. However, the expression ratios were markedly different for the rat and sheep (4.5 vs 1.0, respectively). We conclude that during follicular development, rat oocytes secrete little, if any, BMP15 and that GDF9 without BMP15 can stimulate proliferation of rat and ovine GC. In contrast, ovine oocytes secrete both BMP15 and GDF9 and both were found to stimulate proliferation in both ovine and rat GC.
    Reproduction 09/2012; · 3.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Booroola ewes homozygous (BB) for a mutation in the bone morphogenetic protein receptor-1b (BMPR1B) gene exhibit higher ovulation rates, have larger diameter oocytes at earlier stages of follicular development (i.e. Type 3) and smaller diameter follicles at ovulation than wild-type (++) sheep. However, it is not known when BMPR1B is first expressed in the developing ovary or the cell types involved. In addition, the effects of the BMPR1B mutation on primordial (Type 1) follicles or during growth to the Type 3 stage are unknown. In the present study, BB and++fetal ovaries at Days 30-135 of gestation were screened by in situ hybridisation for BMPR1B mRNA. Ovaries from BB and++lambs were examined by microscopy to measure follicular and oocyte ultrastructural characteristics in Type 1-3 follicles. BMPR1B mRNA was observed in ovaries from Day 35 of gestation and was evident in oocytes of newly forming and fully formed Type 1 follicles. In BB animals, the Type 1 follicles had larger mean follicular and oocyte diameters, a greater volume of mitochondria, smooth endoplasmic reticulum and ribosomes and a greater surface area of junctions with the granulosa cells compared with++animals. It is concluded that the BMPR1B mutation alters follicular development from the onset of follicular formation.
    Reproduction Fertility and Development 01/2012; 24(2):353-61. · 2.58 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The transforming growth factor β (TGFB) superfamily proteins bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9), are essential for mammalian fertility. Recent in vitro evidence suggests that the proregions of mouse BMP15 and GDF9 interact with their mature proteins after secretion. In this study, we have actively immunized mice against these proregions to test the potential in vivo roles on fertility. Mice were immunized with either N- or C-terminus proregion peptides of BMP15 or GDF9, or a full-length GDF9 proregion protein, each conjugated to keyhole limpet hemocyanin (KLH). For each immunization group, ovaries were collected from ten mice for histology after immunization, while a further 20 mice were allowed to breed and litter sizes were counted. To link the ovulation and fertility data of these two experimental end points, mice were joined during the time period identified by histology as being the ovulatory period resulting in to the corpora lutea (CL) counted. Antibody titers in sera increased throughout the study period, with no cross-reactivity observed between BMP15 and GDF9 sera and antigens. Compared with KLH controls, mice immunized with the N-terminus BMP15 proregion peptide had ovaries with fewer CL (P<0.05) and produced smaller litters (P<0.05). In contrast, mice immunized with the full-length GDF9 proregion not only had more CL (P<0.01) but also had significantly smaller litter sizes (P<0.01). None of the treatments affected the number of antral follicles per ovary. These findings are consistent with the hypothesis that the proregions of BMP15 and GDF9, after secretion by the oocyte, have physiologically important roles in regulating ovulation rate and litter size in mice.
    Reproduction 11/2011; 143(2):195-201. · 3.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study aimed to determine whether ewes heterozygous (I+) for the Inverdale mutation of the bone morphogenetic protein-15 (BMP15) gene with high natural ovulation rate (OR) show similar sensitivity to nutritional manipulation as non-carriers (++). Increasing pre-mating nutrition results in OR increases in sheep, but whether this effect occurs in ewes with naturally high OR is unknown. Over 2 years, I+ or ++ ewes were given high (ad libitum) or control (maintenance) pasture allowances for 6 weeks prior to mating at a synchronised oestrus, with OR measured 8 days later. The high group increased in weight compared with controls (+5.84kg; P<0.01), accompanied by increased OR (+19%; P<0.01). As well as having higher OR (+45%; P<0.01), I+ ewes responded to increased feed with a larger proportional increase in OR (+27%; P<0.01) compared with the response in ++ ewes (+11%; P<0.05), suggesting an interaction between BMP15 levels and nutritional signals in the follicle to control OR. Although litter size increases only tended to significance (+12%; P=0.06), extra feed resulted in over 50% of I+ ewes giving birth to more than three lambs, compared with 20-31% of I+ ewes on maintenance rations. This information can guide feed management of prolific Inverdale ewes prior to breeding.
    Reproduction Fertility and Development 09/2011; 23(7):866-75. · 2.58 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Two experiments were designed to investigate the administration of intravaginal progesterone in protocols for oestrus and ovulation synchronization in beef heifers. In Experiment 1, cyclic Black Angus heifers (n = 20) received an Ovsynch protocol and were randomly assigned to receive (CIDR-Ovsynch) or not (Ovsynch) a progesterone device between Days 0 and 7. Treatment with a controlled internal drug release (CIDR) device significantly increased the size of the dominant follicle prior to ovulation (12.8 ± 0.4 CIDR-Ovsynch vs 11.4 ± 0.4 Ovsynch) (p < 0.02). Plasma progesterone concentrations throughout the experiment were affected by the interaction between group and day effects (p < 0.004). In Experiment 2, cyclic Polled Hereford heifers (n = 382) were randomly assigned to one of the six treatment groups (3 × 2 factorial design) to receive a CIDR, a used bovine intravaginal device (DIB), or a medroxiprogesterone acetate (MAP) sponge and GnRH analogues (lecirelin or buserelin). All heifers received oestradiol benzoate plus one of the devices on Day 0 and PGF on Day 7 pm (device withdrawal). Heifers were detected in oestrus 36 h after PGF and inseminated 8-12 h later, while the remainder received GnRH 48 h after PGF and were inseminated on Day 10 (60 h). The number of heifers detected in oestrus on Day 8 and conception rate to AI on Day 9 were higher (p < 0.01) in the used-DIB than in the CIDR or MAP groups, while the opposite occurred with the pregnancy rate to FTAI on Day 10 (p < 0.01). There was no effect of progesterone source, GnRH analogue or their interaction on overall pregnancy rates (64.9%). Progesterone treatment of heifers during an Ovsynch protocol resulted in a larger pre-ovulatory follicle in beef heifers. Progesterone content of intravaginal devices in synchronization protocols is important for the timing of AI, as the use of low-progesterone devices can shorten the interval to oestrus.
    Reproduction in Domestic Animals 08/2011; 47(2):230-7. · 1.39 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Sheep with a heterozygous inactivating mutation in the bone morphogenetic protein 15 (BMP15) gene experience an increased ovulation rate during either a natural oestrous cycle or a cycle in which exogenous FSH and eCG (gonadotrophins) are given to induce multiple ovulations. The primary aim of these studies was to determine whether ewes immunised against BMP15 would also show an improved superovulation rate following exogenous gonadotrophin treatment. A secondary aim was to determine the effects of BMP15 immunisation on ovarian follicular characteristics. In most ewes (i.e. > 75%) immunised with a BMP15-keyhole limpet haemocyanin peptide in an oil-based adjuvant in order to completely neutralise BMP15 bioactivity, there was no superovulation response to exogenous gonadotrophins. In ewes treated with exogenous gonadotrophins following a BMP15-BSA peptide immunisation in a water-based adjuvant to partially neutralise BMP15 bioactivity, the ovulation rate response was similar to the control superovulation treatment groups. Characterisation of follicular function revealed that the water-based BMP15-immunised animals had fewer non-atretic follicles 2.5-3.5 or > 4.5  mm in diameter compared with controls. Basal concentrations of cAMP were higher in granulosa cells from animals immunised against BMP15 than control animals. There were no significant differences in the concentrations of cAMP between granulosa cells from BMP15- and control-immunised animals when given FSH or hCG, although there were differences in the proportions of follicles in different size classes that responded to FSH or hCG. Thus, immunisation against BMP15 may have been causing premature luteinisation and thereby limiting the numbers of follicles recruited for ovulation following treatment with exogenous gonadotrophins.
    Reproduction 07/2011; 142(4):565-72. · 3.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are oocyte-secreted factors known to be involved in regulating the proliferation and differentiation of granulosa cells during follicular growth. The aims of this study were to determine the signalling pathways used by recombinant forms of murine and ovine GDF9 and BMP15 in combination (GDF9+BMP15) and the molecular complexes formed by combinations of these factors. Differences in the molecular forms of combinations of murine and ovine GDF9+BMP15 were observed by western blot analysis. Ovine GDF9+BMP15-stimulated (3)H-thymidine uptake was completely blocked by SMAD2/3 and nuclear factor-κB pathway inhibitors and partially blocked by a p38-mitogen-activated protein kinase (MAPK) inhibitor. Thymidine uptake by murine GDF9+BMP15 was reduced by the SMAD2/3 and extracellular signal-regulated kinase-MAPK pathway inhibitors and increased after addition of a c-Jun N-terminal kinase inhibitor. Stimulation of (3)H-thymidine uptake by GDF9+BMP15 from either species was not affected by the SMAD1/5/8 pathway inhibitor. In conclusion, both murine and ovine GDF9+BMP15-stimulated thymidine incorporation in rat granulosa cells was dependent on the SMAD2/3 signalling pathway but not the SMAD1/5/8 pathway. Divergence in the non-SMAD signalling pathways used by murine and ovine GDF9+BMP15 was also evident and may be due to the differences observed in the molecular complexes formed by these factors. These results are consistent with the hypothesis that the disparate cooperative functions of GDF9 and BMP15 in different species are mediated by divergent non-SMAD signalling pathways.
    Reproduction 04/2011; 142(1):123-31. · 3.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to test the hypothesis that the high ovulation rate in ewes (BB) homozygous for a mutation in the bone morphogenetic protein receptor type 1B (BMPR1B) gene is linked to lower BMP15 and/or GDF9 mRNA in oocytes compared with those in wild-type (++) ewes. Cumulus cell-oocyte complexes (COC) and granulosa cells (GC) were recovered from ≥1 mm diameter follicles of BB and ++ ewes during a prostaglandin-induced follicular phase. Expression levels of GDF9 and BMP15 were measured by multiplex qPCR from individual COC. The gonadotropin-induced cAMP responses of the GC from each non-atretic follicle were measured following treatment with FSH or human chorionic gonadotropin. In a separate validation experiment, GDF9 and BMP15 expression was present only in oocytes and not in cumulus cells. There was no effect of follicular diameter on oocyte-derived GDF9 or BMP15 mRNA levels. The mean expression levels of BMP15, but not GDF9, were significantly lower in all non-atretic follicles, including the subsets containing either FSH- or LH-responsive GC in BB, compared with ++, ewes. No genotype effects were noted for FSH-induced cAMP production by GC either with respect to dose of, or number of follicles responding to, FSH. However, ovaries from BB ewes contained significantly more follicles responsive to LH, with respect to cAMP production in GC. We propose that these findings are consistent with the hypothesis that the higher ovulation rate in BB sheep is due, at least in part, to lower oocyte-derived BMP15 mRNA levels together with the earlier onset of LH-responsiveness in GC.
    Reproduction 04/2011; 142(1):53-61. · 3.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Sheep lines with mutations in single genes that have major effects on ovulation rate have been very useful in gaining a better understanding of pathways important in controlling follicular development and ovulation rate. To date however, all known mutations are in the transforming growth factor beta (TGFB) superfamily. Ovulation rates were measured in 720 progeny of 20 rams that were descendants of a single prolific ewe. Evaluation of ovulation rates of daughters of closely related sires suggests the presence of a segregating major gene Fecundity Davisdale (FECD) that increases ovulation rate between 0.4 and 0.8 in heterozygous daughters. Key features of mutations in genes of the TGFB superfamily pathway, such as synergistic interactions with other family members, infertility in homozygous carriers, and increased responsiveness to exogenous gonadotropins, were not observed in this line; thus, the mutation does not appear to be acting in the TGFB pathway. Hence, there is likely a novel mutation being carried in this line of sheep that alters ovulation rate. Future identification of the causative mutation may provide new insights into regulation of follicular development and ovulation rate.
    Biology of Reproduction 03/2011; 85(1):113-20. · 4.03 Impact Factor

Publication Stats

3k Citations
367.59 Total Impact Points

Institutions

  • 2001–2013
    • AgResearch
      • Reproductive and Developmental Biology Team
      Hamilton City, Waikato, New Zealand
  • 2006–2011
    • Victoria University of Wellington
      • School of Biological Sciences
      Wellington, Wellington, New Zealand
  • 1993–2009
    • University of Missouri
      • Division of Animal Sciences
      Columbia, MO, United States
  • 2002
    • University of Otago
      • Department of Biochemistry
      Dunedin, Otago, New Zealand
  • 1994–2002
    • Colorado State University
      • • Chemistry
      • • College of Veterinary Medicine and Biomedical Sciences
      Fort Collins, Colorado, United States
  • 1998
    • National Cheng Kung University
      • Department of Physiology
      Tainan, Taiwan, Taiwan
  • 1997
    • University of Wisconsin, Madison
      • Department of Dairy Science
      Madison, MS, United States