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1.
J Anim Sci ; 91(10): 4641-53, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23942709

RESUMO

The goal was to estimate the heritabilities and genetic variances for embryo and fetal survival (ES) in sheep along with the effect of premating ewe weight, age, and bilateral or 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 yr 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 yr, respectively. Litter size was less in ewes of age 2 and 6 yr compared to ewes of age 3, 4, and 5 yr (P < 0.01). Ovulation rate was lower at age 2 yr and increased from age 2 to 6 yr (P < 0.05). Two-year-old ewes had lower ES than 3-yr-old ewes (P < 0.01) and the probability of ES decreased after age 3 yr (P < 0.01). Thus, ES contributes significantly to lower fertility in 2-yr-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 or 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.


Assuntos
Envelhecimento/fisiologia , Peso Corporal/fisiologia , Desenvolvimento Embrionário/genética , Desenvolvimento Fetal/genética , Prenhez , Ovinos/fisiologia , Aborto Animal , Envelhecimento/genética , Animais , Peso Corporal/genética , Feminino , Fertilidade , Variação Genética , Tamanho da Ninhada de Vivíparos , Masculino , Modelos Biológicos , Ovulação , Gravidez , Taxa de Gravidez , Prenhez/genética , Prenhez/fisiologia , Ovinos/embriologia , Ovinos/genética
2.
J Theor Biol ; 266(1): 62-9, 2010 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-20553942

RESUMO

In this paper we develop a mathematical model of the luteal phase of the reproductive cycle in mammals with the aim to generate a systems understanding of pregnancy recognition. Pregnancy recognition is initiated by the production of interferon tau (IFNtau) by the growing conceptus. This ensures that the maternal corpus luteum (CL) remains viable to secrete progesterone, which is critical for providing a uterine microenvironment suitable for embryonic growth. Our mathematical model describes the interactions among the CL, the reproductive hormones and the hormone receptors in the uterus. It also characterises the complex interactions amongst the uterine oestrogen, progesterone and oxytocin receptors that control the sensitivity of the uterus to oestrogen, progesterone and oxytocin, respectively. The model is represented by a dynamical system and exhibits qualitative features consistent with the known experimental results in sheep. A key factor identified was a time-dependent threshold for the IFNtau signal below which the presence of the embryo might not be recognised and thus pregnancy would likely fail. Furthermore, the model indicated that if the IFNtau signal is later than around day 13 of the cycle, then pregnancy will not be recognised irrespective of the IFNtau concentration. The thresholds in the concentration and time of the IFNtau signal is a screening mechanism whereby only embryos of sufficient quality are able to prevent luteolysis (i.e. regression of the CL). The effect of progesterone secretion rate from the CL on pregnancy recognition was investigated. The model suggests that if the secretion rate is low then the initiation of the IFNtau signal is delayed, which in turn compromises the likelihood of a pregnancy being recognised by the CL. Furthermore, pregnancy recognition does not occur below a critical threshold in the progesterone secretion rate. In summary, the model can be used to identify the most favourable conditions for pregnancy recognition.


Assuntos
Mamíferos/metabolismo , Modelos Biológicos , Gravidez/metabolismo , Algoritmos , Animais , Simulação por Computador , Corpo Lúteo/crescimento & desenvolvimento , Corpo Lúteo/metabolismo , Dinoprosta/metabolismo , Embrião de Mamíferos/metabolismo , Estrogênios/metabolismo , Feminino , Interferon Tipo I/metabolismo , Fase Luteal/metabolismo , Luteólise/metabolismo , Ocitocina/metabolismo , Proteínas da Gravidez/metabolismo , Progesterona/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Ocitocina/metabolismo , Receptores de Progesterona/metabolismo , Ovinos/metabolismo , Fatores de Tempo , Útero/metabolismo
3.
Biochim Biophys Acta ; 1773(10): 1491-9, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17888529

RESUMO

The morphological features observed by Kerr, Wylie and Currie in 1972 define apoptosis, necrosis and autophagy. An appreciable number of alternative systems do not fall neatly under these categories, warranting a review of alternative proteolytic machinery and its contribution to cell death. This review aims to pinpoint key molecular features of serine protease-mediated pro-apoptotic signalling. The profile created will contribute to a standard set of biochemical criteria that can serve in differentiating within cell death subtypes.


Assuntos
Morte Celular/fisiologia , Serina Endopeptidases/fisiologia , Animais , Apoptose/fisiologia , Granzimas/metabolismo , Serina Peptidase 2 de Requerimento de Alta Temperatura A , Humanos , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Serina Endopeptidases/metabolismo , Transdução de Sinais , Ativador de Plasminogênio Tipo Uroquinase/metabolismo
4.
Biochem Biophys Res Commun ; 345(2): 608-16, 2006 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-16690028

RESUMO

Apoptosis involves a cascade of biochemical and morphological changes resulting in the systematic disintegration of the cell. Caspases are central mediators of this process. Supporting and primary roles for serine proteases as pro-apoptotic mediators have also been highlighted. Evidence for such roles comes largely from the use of pharmacological inhibitors; as a consequence information regarding their apoptotic function and biochemical properties has been limited. Here, we circumvented limitations associated with traditional serine protease inhibitors through use of a fluorescently labelled inhibitor of serine proteases (FLISP) that allowed for analysis of the specificity, regulation and positioning of apoptotic serine proteases within a classical apoptotic cascade. We demonstrate that staurosporine triggers a caspase-dependant induction of chymotrypsin-like activity in the nucleus of apoptotic Jurkat T cells. We show that serine protease activity is required for the generation of late stage nuclear events including condensation, fragmentation and DNA degradation. Furthermore, we reveal caspase-dependant activation of two chymotrypsin-like protein species that we hypothesize mediate cell death-associated nuclear events.


Assuntos
Apoptose/fisiologia , Caspases/metabolismo , Núcleo Celular/fisiologia , Quimotripsina/metabolismo , Células Jurkat/enzimologia , Apoptose/efeitos dos fármacos , Inibidores de Caspase , Núcleo Celular/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Fragmentação do DNA/fisiologia , Ativação Enzimática , Corantes Fluorescentes , Humanos , Células Jurkat/citologia , Inibidores de Serina Proteinase/farmacologia , Estaurosporina/farmacologia , Especificidade por Substrato
5.
Anim Reprod Sci ; 92(1-2): 65-73, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15998568

RESUMO

Ovulation rates were measured in 547 progeny of 24 rams in a Romney flock with a long history of high prolificacy. These sheep were from the same family line and the distribution of ovulation rates suggests the presence of a segregating major gene (FecW) that increases prolificacy. The phenotype differs from those previously described for major genes affecting prolificacy in sheep. The putative gene shows autosomal inheritance and one copy increases ovulation rate by 0.8-1.0 eggs per ewe ovulating. To date, we have found no evidence of infertility among putative homozygous ewes, as described in some autosomal major genes for prolificacy.


Assuntos
Ovulação/genética , Ovinos/genética , Animais , Feminino , Tamanho da Ninhada de Vivíparos/genética , Tamanho da Ninhada de Vivíparos/fisiologia , Masculino , Ovulação/fisiologia , Linhagem , Gravidez , Ovinos/fisiologia
6.
Exp Cell Res ; 312(1): 27-39, 2006 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-16288739

RESUMO

Tightly controlled proteolysis is a defining feature of apoptosis and caspases are critical in this regard. Significant roles for non-caspase proteases in cell death have been highlighted. Staurosporine causes a rapid induction of apoptosis in virtually all mammalian cell types. Numerous studies demonstrate that staurosporine can activate cell death under caspase-inhibiting circumstances. The aim of this study was to investigate the proteolytic mechanisms responsible for cell death under these conditions. To that end, we show that inhibitors of serine proteases can delay cell death in one such system. Furthermore, through profiling of proteolytic activation, we demonstrate, for the first time, that staurosporine activates a chymotrypsin-like serine protease-dependent cell death in HL-60 cells independently, but in parallel with the caspase controlled systems. Features of the serine protease-mediated system include cell shrinkage and apoptotic morphology, regulation of caspase-3, altered nuclear morphology, generation of an endonuclease and DNA degradation. We also demonstrate a staurosporine-induced activation of a putative 16 kDa chymotrypsin-like protein during apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Serina Endopeptidases/fisiologia , Inibidores de Serina Proteinase/farmacologia , Western Blotting , Caspase 3 , Inibidores de Caspase , Caspases/metabolismo , Quimases , Células HL-60/enzimologia , Células HL-60/patologia , Humanos , Serina Endopeptidases/metabolismo , Estaurosporina/farmacologia , Frações Subcelulares
7.
Biol Reprod ; 64(4): 1225-35, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11259271

RESUMO

The Booroola fecundity gene (FecB) increases ovulation rate and litter size in sheep and is inherited as a single autosomal locus. The effect of FecB is additive for ovulation rate (increasing by about 1.6 corpora lutea per cycle for each copy) and has been mapped to sheep chromosome 6q23-31, which is syntenic to human chromosome 4q21-25. Bone morphogenetic protein IB (BMP-IB) receptor (also known as ALK-6), which binds members of the transforming growth factor-beta (TGF-beta) superfamily, is located in the region containing the FecB locus. Booroola sheep have a mutation (Q249R) in the highly conserved intracellular kinase signaling domain of the BMP-IB receptor. The mutation segregated with the FecB phenotype in the Booroola backcross and half-sib flocks of sheep with no recombinants. The mutation was not found in individuals from a number of sheep breeds not derived from the Booroola strain. BMPR-IB was expressed in the ovary and in situ hybridization revealed its specific location to the oocyte and the granulosa cell. Expression of mRNA encoding the BMP type II receptor was widespread throughout the ovary. The mutation in BMPR-IB found in Booroola sheep is the second reported defect in a gene from the TGF-beta pathway affecting fertility in sheep following the recent discovery of mutations in the growth factor, GDF9b/BMP15.


Assuntos
Células da Granulosa/química , Oócitos/química , Mutação Puntual , Proteínas Serina-Treonina Quinases/genética , Ovinos/genética , Receptores de Ativinas , Sequência de Aminoácidos , Animais , Proteínas Morfogenéticas Ósseas/fisiologia , Tamanho Celular , Mapeamento Cromossômico , Sequência Conservada , DNA Complementar/química , Feminino , Expressão Gênica , Genótipo , Humanos , Masculino , Dados de Sequência Molecular , Oócitos/citologia , Ovulação/genética , Polimorfismo de Fragmento de Restrição , Proteínas Quinases/química , Proteínas Quinases/genética , Proteínas Serina-Treonina Quinases/química , RNA Mensageiro/análise , Análise de Sequência de DNA , Homologia de Sequência , Ovinos/fisiologia , Transdução de Sinais
8.
Domest Anim Endocrinol ; 16(1): 69-80, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10081664

RESUMO

We have tested the hypothesis "that the ovulation rate in homozygous carriers (BB) and noncarriers (+2) of the Booroola FecB gene would not be different if the plasma concentrations of follicle-stimulating hormone (FSH) in the two genotypes were similar." For this purpose we used two experimental animal models: 1) the hypothalamic-pituitary disconnected (HPD) ovary-intact ewe; and 2) and GnRH agonist (i.e., Deslorelin)-treated ewe. Following HPD or Deslorelin treatment, the animals had low plasma concentrations of gonadotropins and were anovulatory. In both animal models, BB and +2 ewes were treated with exogenous pregnant mares serum gonadotropin (PMSG) and varying doses of FSH to induce preovulatory follicular growth, and human chorionic gonadotropin (hCG) to induce ovulation. HPD or Deslorelin-treated animals administered with pregnant mares serum gonadotropin without FSH followed by human chorionic gonadotropin failed to ovulate. However for both animal models, the proportion of BB and +2 ewes ovulating to various doses of FSH differed such that significantly greater proportions of +2 animals ovulated relative to the BB genotype (P < 0.05). When HPD or Deslorelin-treated BB and +2 ewes were administered identical doses of FSH, the mean ovulation rate and plasma concentrations of FSH in those animals which ovulated was the same in both genotypes. These findings confirm, at least in part, the aforementioned hypothesis. The results also demonstrated that higher ovulation rates were obtained in both genotypes as the FSH dose was increased. Collectively, these findings infer that the higher mean ovulation rate in normal intact BB ewes compared to the +2 genotype is attributable to effects of the FecB gene at the level of ovarian follicular development as well as at the level of pituitary FSH release.


Assuntos
Proteínas de Bactérias/genética , Proteínas de Transporte/genética , Proteínas de Escherichia coli , Hormônio Foliculoestimulante/farmacologia , Hormônio Liberador de Gonadotropina/agonistas , Sistema Hipotálamo-Hipofisário/fisiologia , Bombas de Íon , Ovulação/efeitos dos fármacos , Ovinos/genética , Animais , Anovulação , Gonadotropina Coriônica/farmacologia , Feminino , Hormônio Foliculoestimulante/administração & dosagem , Hormônio Foliculoestimulante/sangue , Genótipo , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/farmacologia , Homozigoto , Sistema Hipotálamo-Hipofisário/cirurgia , Hormônio Luteinizante/sangue , Ovulação/genética , Gravidez , Pamoato de Triptorrelina/análogos & derivados
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