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1.
Gene ; 766: 145158, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32949694

RESUMO

The reproductive performance (e.g. fertility) of dairy cows, which declined over past few decades due to the intense and intensive selection, needs to be improved. Previous genome-wide association study (GWAS) of female Holstein screened the Adenylate cyclase 5 (ADCY5) as the candidate gene for cow fertility. As a member of the adenylyl cyclases family, adenylate cyclase 5 (ADCY5) is famous for regulating extrapyramidal motor system related various neuropsychiatric diseases, and its genetic variant is reported to associate with lower birth and placenta weight which leads to asymmetric fetal growth restriction. It was hypothesized that ADCY5 may affect the fertility of cows by regulating the processes of ovarian development. Herein, genomic DNA from 768 ovaries samples of healthy unrelated Holstein cow were used to screen potential insertion/deletion (indel) mutations using eight pairs of primers, and we found three novel polymorphic indel variants, namely, rs385624978 (P3-D11-bp), rs433028962 (P5-I19-bp) and rs382393457 (P8-D19-bp). The minor allelic frequencies (MAF) of P3-D11-bp, P5-I19-bp and P8-D19-bp loci were 0.188, 0.365 and 0.06, respectively, and there were 7 different haplotypes. Additionally, linkage disequilibrium analysis demonstrated no linkage among them. Importantly, P3-D11-bp locus was significantly related to both ovarian width (P = 1.0E-6) and corpus luteum diameter (P = 0.015); P5-I19-bp locus had a significant relation with corpus albicans diameter (P = 0.030) and ovaries with mutational homozygous genotype produced a superior corpus albicans diameter than those with other genotypes. Briefly, three novel indel mutations of bovine ADCY5 gene were identified and two of them were uncovered to be significantly correlated with ovarian phenotypic traits or corpus luteum or albicans traits. These findings contributed to the application of molecular marker-assisted selection (MAS) in improving female fertility in cattle, which could accelerate the development of the cattle industry.


Assuntos
Adenilil Ciclases/genética , Ovário/fisiologia , Polimorfismo de Nucleotídeo Único/genética , Animais , Bovinos , Feminino , Fertilidade/genética , Frequência do Gene/genética , Estudo de Associação Genômica Ampla/métodos , Genótipo , Haplótipos/genética , Mutação INDEL/genética , Desequilíbrio de Ligação/genética , Fenótipo , Reprodução/genética
2.
PLoS One ; 15(10): e0239779, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33044971

RESUMO

BACKGROUND: The conditions of diminished ovarian reserve and primary ovarian insufficiency, characterized by poor fertility outcomes, currently comprise a major challenge in reproductive medicine, particularly in vitro fertilization. Currently in the IVF industry, blastocyst developmental success rate per treatment is routinely overlooked when a live birth results from treatment. Limited data are available on this significant and actionable variable of blastocyst development optimization, which contributes to improvement of treatment success Women with elevated basal FSH concentration are reported to still achieve reasonable pregnancy rates, although only a few studies report correlations with blastocysts development. Diagnostic values of AMH/basal FSH concentrations can be useful for determining the optimal stimulation protocol as well as identification of individuals who will not benefit from IVF due to poor prognosis. The objective of this study is to identify actionable clinical and culture characteristics of IVF treatment that influence blastocyst developmental rate, with the goal of acquiring optimal success. METHODS AND FINDINGS: A retrospective observational study was performed, based on 106 women undergoing IVF, regardless of prognosis, over a six-month period from January 1, 2015 to June 31, 2015. Rate of high-quality blastocyst production, which can be used for embryo transfer or vitrification, per normally fertilized oocyte, was evaluated. Treatment was determined successful when outcome was ≥ 40% high-quality blastocysts. The data were initially evaluated with the Evtree algorithm, a statistical computational analysis which is inspired by natural Darwinian evolution incorporating concepts such as mutation and natural selection (see Supplementary Material). The analysis processes all variables simultaneously against the outcome, aiming to maximize discrimination of each variable to then create a "branch" of the tree which can be used as a decision in treatment. The final model results in only those variables which are significant to outcomes. Generalized linear model (GLM) employing logistic regression and survival analysis with R software was used and the final fitting of the model was determined through the use of random forest and evolutionary tree algorithms. Individuals presenting with an [AMH] of >3.15 ng/ml and a good prognosis had a lower success per treatment (n = 11, 0% success) when total gonadotropin doses were greater than 3325 IU. Individuals that presented with an [AMH] of <1.78 ng/ml and a poor prognosis exhibited a greater success per treatment (n = 11, 80% success). AMH emerged as a superior indicator of blastocyst development compared to basal FSH. The accuracy of the prediction model, our statistical analysis using decision tree, evtree methodology is 86.5% in correctly predicting outcome based on the significant variables. The likelihood that the outcome with be incorrect of the model, or the error rate is 13.5%. CONCLUSIONS: [AMH] is a superior indicator of ovarian stimulation response and an actionable variable for stimulation dose management for optimizing blastocyst development in culture. Women whose [AMH] is ≥3.2 mg/ml, having a good prognosis, and developing >12 mature follicles result in <40% blastocysts when gonadotropin doses exceed 3325 IU per treatment. IVF treatments for poor responders that present with infertility due to diminished ovarian reserve, if managed appropriately, can produce more usable blastocyst per IVF treatment, thus increasing rate of blastocyst developmental success and ultimately increasing live birth rates. Future studies are needed to investigate the intra-follicular and the intra-cellular mechanisms that lead to the inverse relationship of blastocysts development and total gonadotropin doses in good responders in contrast to poor responders.


Assuntos
Hormônio Antimülleriano/sangue , Blastocisto/metabolismo , Blastocisto/fisiologia , Desenvolvimento Embrionário/fisiologia , Hormônio Foliculoestimulante/sangue , Adulto , Transferência Embrionária/métodos , Feminino , Fertilização In Vitro/métodos , Humanos , Infertilidade/sangue , Infertilidade/terapia , Nascimento Vivo , Masculino , Folículo Ovariano/metabolismo , Reserva Ovariana/fisiologia , Ovário/metabolismo , Ovário/fisiologia , Indução da Ovulação/métodos , Gravidez , Taxa de Gravidez , Estudos Retrospectivos
3.
Chemosphere ; 258: 127361, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32947662

RESUMO

In female mammals, puberty and fertility are regulated by the synthesis of estradiol (E2) by the ovaries at the infantile stage and at the approach of puberty, a process which may be affected by endocrine disrupting chemicals (EDC)s acting through the Aryl hydrocarbon receptor (AhR). However, there is no information on AhR-mediated regulation of ovarian estrogenic activity during these developmental periods. Here, we assessed in mouse models, the intrinsic and exogenous ligand-induced AhR action on E2 synthesis at the infantile stage (14 days postnatal (dpn)) and at the approach of puberty (28 dpn). Intrinsic AhR pathway became activated in the ovary at the approach of puberty, as suggested by the decreased intra-ovarian expression in prototypical and steroidogenesis-related AhR targets and E2 contents in Ahr knockout (Ahr-/-) mice versus Ahr+/+ mice exclusively at 28 dpn. Accordingly, AhR nuclear localization in granulosa cells, reflecting its activity in cells responsible for E2 synthesis, was much lower at 14 dpn than at 28 dpn in C57BL/6 mice. However, AhR signaling could be activated by exogenous ligands at both ages, as revealed by FICZ- and TCDD-induced Ahrr and Cyp1a1 expression in C57BL/6 mice. Nevertheless, TCDD impacted ovarian estrogenic activity only at 28 dpn. This age-related AhR action may be ligand-dependent, since FICZ had no effect on E2 synthesis at 28 dpn. In conclusion, AhR would not regulate ovarian estrogenic activity before the approach of puberty. Its activation by EDCs may be more detrimental to reproductive health at this stage than during infancy.


Assuntos
Ovário/fisiologia , Dibenzodioxinas Policloradas/toxicidade , Receptores de Hidrocarboneto Arílico/metabolismo , Animais , Citocromo P-450 CYP1A1/metabolismo , Disruptores Endócrinos/metabolismo , Estradiol/metabolismo , Estrogênios/farmacologia , Feminino , Células da Granulosa/efeitos dos fármacos , Ligantes , Camundongos , Camundongos Endogâmicos C57BL , Ovário/efeitos dos fármacos , Dibenzodioxinas Policloradas/metabolismo , Maturidade Sexual/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
4.
Adv Exp Med Biol ; 1252: 175-179, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32816279

RESUMO

Malignancy may unfortunately present quite early in a woman's life. In the case of breast cancer, rescue of the breast cancer patient's life is the top priority, but after completion of the effective treatment , the question about the ability to accomplish a pregnancy arises. The treatment strategies in breast cancer patients include surgical interventions, chemotherapy , radiotherapy, hormonal therapy and other special types of mainly targeted biologic therapies. Under normal circumstances, surgery for breast cancer does not involve any intervention in the ovaries or the uterus. Thus, even after an extended operation, the anatomic integrity of the gynecological system is guaranteed, and fertility is unaffected.The chemotherapeutic factors that influence fertility are the drug category used, the total dose given, the patient's age at treatment , the drug combination and finally whether targeted therapy is used or not. Alkylating agents are considered to be the most toxic ones. In young breast cancer patients there is a trend to modify regimens to achieve less gonadotoxicity.Evidence regarding tamoxifen, the main used endocrine drug, is scarce and controversial on its direct effect on ovarian reserve. There are not enough studies on the impact of aromatase inhibitors on fertility. Also, HER2-directed agents have not yet demonstrated significant ovarian toxicity and there are scarce data on their effect on fertility.


Assuntos
Neoplasias da Mama/terapia , Preservação da Fertilidade , Fertilidade/fisiologia , Inibidores da Aromatase/efeitos adversos , Feminino , Humanos , Infertilidade Feminina/etiologia , Reserva Ovariana/efeitos dos fármacos , Ovário/efeitos dos fármacos , Ovário/fisiologia , Gravidez , Tamoxifeno/efeitos adversos
5.
PLoS One ; 15(8): e0237032, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790683

RESUMO

The behavioral activation system (BAS) and the behavioral inhibition system (BIS) have been proposed to relate to stable traits that predict inter-individual differences in motivation. Prior reports point dopamine (DA) pathways, mainly including ventral tegmental area (VTA) and substantia nigra (SN), implicate in subserving reward-related functions associated with BAS and inhibitory functions related with BIS. However, as an important factor that affects DA releasing, it remains an open question whether the ovarian hormones may also be related to BIS/BAS. Here, to investigate effects of the estradiol (E2) and progesterone (PROG) on BIS/BAS and related DA pathways, we employed a BIS/BAS scale and the resting-state functional magnetic resonance imaging (fMRI) during the late follicular phase (FP) and the mid-luteal phase (LP). On the behavioral level, when women had high PROG levels, their E2 levels were found positively correlated with BIS scores, but those women whose PROG levels were low, their E2 levels were negative correlation with BIS scores. On the neural level, we demonstrated BAS was related with the VTA pathway, included brain reward regions of nucleus accumbens (NAc) and orbitofrontal cortex (OFC). Meanwhile, the BIS was correlated with the SN-dorsolateral prefrontal cortex (dlPFC) pathway. ROI-based resting-state functional connectivity (RSFC) analyses further revealed that, RSFC between the SN and dlPFC was modulated by ovarian hormones. With higher PROG levels, increased E2 levels among women were accompanied by stronger RSFC of the SN-dlPFC, but when PROG levels were low, E2 levels were negatively correlated with the SN-dlPFC RSFC. These findings revealed a combined enhancement effect of E2 and PROG on BIS, and the SN-dlPFC pathway was mainly involved in this process.


Assuntos
Encéfalo/fisiologia , Dopamina/fisiologia , Inibição Psicológica , Motivação/fisiologia , Ovário/fisiologia , Adulto , Afeto/fisiologia , Encéfalo/diagnóstico por imagem , Neurônios Dopaminérgicos/fisiologia , Estradiol/fisiologia , Feminino , Neuroimagem Funcional , Humanos , Imagem por Ressonância Magnética , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiologia , Progesterona/fisiologia , Psicofisiologia , Substância Negra/diagnóstico por imagem , Substância Negra/fisiologia , Área Tegmentar Ventral/diagnóstico por imagem , Área Tegmentar Ventral/fisiologia , Adulto Jovem
6.
Adv Exp Med Biol ; 1207: 463-466, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32671768

RESUMO

Polycystic Ovary Syndrome (PCOS) is a common obesity-related reproductive disease in women of child-bearing age,which is usually accompanied with endocrine and metabolic abnormalities such as hyperandrogenemia and hyperinsulinemia. The abnormal reproductive function of PCOS is mainly characterized by the morphological and functional changes of ovary. Autophagy is involved in the maintenance of human ovarian physiological function as well as in the process of luteal degeneration, and affects the survival of granulosa cells. This chapter introduces the latest research progress of the relationship between autophagy and PCOS. How autophagy is involved in the occurrence and development of PCOS remains to be further studied.


Assuntos
Autofagia , Síndrome do Ovário Policístico , Feminino , Células da Granulosa , Humanos , Hiperandrogenismo/complicações , Hiperinsulinismo/complicações , Obesidade/complicações , Ovário/patologia , Ovário/fisiologia , Ovário/fisiopatologia , Síndrome do Ovário Policístico/complicações
7.
J Vis Exp ; (161)2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32716390

RESUMO

The limited reserve of mature, fertilizable oocytes represents a major barrier for the success of assisted reproduction in mammals. Considering that during the reproductive life span only about 1% of the oocytes in an ovary mature and ovulate, several techniques have been developed to increase the exploitation of the ovarian reserve to the growing population of non-ovulatory follicles. Such technologies have allowed interventions of fertility preservation, selection programs in livestock, and conservation of endangered species. However, the vast potential of the ovarian reserve is still largely unexploited. In cows, for instance, some attempts have been made to support in vitro culture of oocytes at specific developmental stages, but efficient and reliable protocols have not yet been developed. Here we describe a culture system that reproduce the physiological conditions of the corresponding follicular stage, defined to develop in vitro growing oocytes collected from bovine early antral follicles to the fully-grown stage, corresponding to the medium antral follicle in vivo. A combination of hormones and a phosphodiesterase 3 inhibitor was used to prevent untimely meiotic resumption and to guide oocyte's differentiation.


Assuntos
Técnicas de Cultura de Células/métodos , Oócitos/fisiologia , Reserva Ovariana/fisiologia , Reprodução/fisiologia , Animais , Bovinos , Ciclo Celular/fisiologia , Diferenciação Celular/fisiologia , Feminino , Oogênese/fisiologia , Folículo Ovariano/fisiologia , Ovário/citologia , Ovário/fisiologia
8.
Poult Sci ; 99(5): 2708-2717, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32359608

RESUMO

Brooding behavior, a common characteristic of native breeds of the domestic chicken, is marked by elevated prolactin (PRL) levels, which is necessary for incubation and connected with changes in hypothalamic-pituitary-gonadal axis activity. Evidence indicates the serotoninergic system is a potent modulator of PRL secretion. The objective of this study is to investigate whether blocking serotonin synthesis with parachlorophenylalanine (PCPA) prevents incubation behavior in native Polish crested chickens. In addition, we examined the effect of PCPA on the gene expression of the gonadal and lactotrophic axes. Birds were stimulated to broodiness by artificial eggs in nests. At 34 wk of age (April: spring period), the hens were divided into 2 groups (14 hens in each group): control and PCPA-treated (50 mg/kg BW) group. After 5 wk of treatment, the artificial eggs were removed from the nests. Egg production, incubation activity, and levels of plasma ovarian steroids progesterone (P4), testosterone (T), estradiol (E2), and PRL were examined. At the end of the experiment (45 wk of age, June: summer period), ovarian characteristics and mRNA gene expression of gonadal (gonadotropin-releasing hormone [GnRH] I, luteinizing hormone [LH] ß, follicle-stimulating hormone [FSH] ß) and lactotrophic (vasoactive intestinal peptide [VIP], PRL) axes were measured by quantitative real-time PCR. Incubation activity was observed in the hens of both groups but with lower frequency in PCPA-treated birds. Moreover, the PCPA group had a higher cumulative egg production than the controls. During the first six and 8 wk of the experiment, levels of P4 and E2, respectively, were similar in both groups, but all concentrations increased in the PCPA-treated hens after this period. In addition, increased GnRH-I, LHß, and FSHß and decreased VIP mRNA expression was observed in the PCPA group compared with the controls. There were no differences in PRL mRNA expression, the PRL level, and ovarian morphometry between the 2 groups. These results indicate that blockage of serotonin synthesis by PCPA does not effectively prevent incubation in native Polish crested chickens. However, treatment with PCPA increased gonadal axis activity and improved reproductive performance.


Assuntos
Galinhas/fisiologia , Fenclonina/farmacologia , Lactotrofos/efeitos dos fármacos , Comportamento de Nidação/efeitos dos fármacos , Ovário/efeitos dos fármacos , Antagonistas da Serotonina/farmacologia , Animais , Feminino , Lactotrofos/fisiologia , Ovário/fisiologia , Polônia , Serotonina/metabolismo
9.
Nat Rev Endocrinol ; 16(8): 407-420, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32427949

RESUMO

Hypothalamic kisspeptin neurons serve as the nodal regulatory centre of reproductive function. These neurons are subjected to a plethora of regulatory factors that ultimately affect the release of kisspeptin, which modulates gonadotropin-releasing hormone (GnRH) release from GnRH neurons to control the reproductive axis. The presence of sufficient energy reserves is critical to achieve successful reproduction. Consequently, metabolic factors impose a very tight control over kisspeptin synthesis and release. This Review offers a synoptic overview of the different steps in which kisspeptin neurons are subjected to metabolic regulation, from early developmental stages to adulthood. We cover an ample array of known mechanisms that underlie the metabolic regulation of KISS1 expression and kisspeptin release. Furthermore, the novel role of kisspeptin neurons as active players within the neuronal circuits that govern energy balance is discussed, offering evidence of a bidirectional role of these neurons as a nexus between metabolism and reproduction.


Assuntos
Metabolismo Energético/fisiologia , Kisspeptinas/fisiologia , Reprodução/fisiologia , Animais , Dinorfinas/fisiologia , Feminino , Hormônio Liberador de Gonadotropina/fisiologia , Homeostase , Humanos , Sistema Hipotálamo-Hipofisário/fisiologia , Hipotálamo/citologia , Hipotálamo/fisiologia , Kisspeptinas/genética , Hormônio Luteinizante/fisiologia , Neurocinina B/fisiologia , Neurônios/fisiologia , Ovário/fisiologia , Puberdade/fisiologia
10.
Poult Sci ; 99(4): 2185-2195, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32241504

RESUMO

The signal pathway of target of rapamycin (TOR) plays an important role in regulating cell growth and proliferation, follicular development, and ovulation. Melatonin (N-acetyl-5-methoxytryptamine) (MT) is involved in the regulation of many physiological functions in animals. Recent studies have shown that MT affects the number and the degree of maturation of follicles in the ovary, but there are few studies concerning its mechanism. Therefore, the aim of this study was to investigate the mechanism of TOR signal pathway in the regulation of ovarian function by MT in aging laying hens. In the present study, a total of 60 hens (70-week-old) were randomly divided into 2 groups: control group and melatonin group (M). Melatonin was administered intraperitoneally at a dose of 20 mg/kg/D for 28 D in the M group. The results showed that MT significantly increased the levels of the antioxidant enzymes superoxide dismutase and total antioxidant capacity (P < 0.01) as well as levels of immunoglobulin (IgA, IgG, and IgM) (P < 0.05) and the reproductive hormones estradiol and luteinizing hormone (P < 0.01) in the plasma and also increased the numbers of middle white follicles and small white follicles (P < 0.05) and decreased the level of reactive oxygen species in plasma (P < 0.01) in laying hens. There were higher expression levels in MT receptor A (P < 0.05), melatonin receptor B (P < 0.01), and tuberous sclerosis complex 2 (P < 0.01). Activation of TOR, 4E binding protein-l (4E-BP1), and ribosomal protein 6 kinase (P < 0.01) was found in the M. The levels of mTOR and p-mTOR protein were increased in the M (P < 0.05). The mTORC1-dependent 4E-BP1 and p-4E-BP1 were increased in the M (P < 0.05). This study indicated that MT may enhance follicle growth by increasing levels of antioxidant enzymes and reproductive hormones and by activating the mTOR and downstream components in aging laying hens.


Assuntos
Antioxidantes/farmacologia , Galinhas/fisiologia , Melatonina/farmacologia , Folículo Ovariano/crescimento & desenvolvimento , Ovário/fisiologia , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Animais , Antioxidantes/administração & dosagem , Proteínas Aviárias/metabolismo , Feminino , Injeções Intraperitoneais/veterinária , Melatonina/administração & dosagem , Folículo Ovariano/efeitos dos fármacos , Ovário/efeitos dos fármacos , Distribuição Aleatória
11.
PLoS Biol ; 18(4): e3000538, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32339165

RESUMO

Oogenesis is a complex developmental process that involves spatiotemporally regulated coordination between the germline and supporting, somatic cell populations. This process has been modeled extensively using the Drosophila ovary. Although different ovarian cell types have been identified through traditional means, the large-scale expression profiles underlying each cell type remain unknown. Using single-cell RNA sequencing technology, we have built a transcriptomic data set for the adult Drosophila ovary and connected tissues. Using this data set, we identified the transcriptional trajectory of the entire follicle-cell population over the course of their development from stem cells to the oogenesis-to-ovulation transition. We further identify expression patterns during essential developmental events that take place in somatic and germline cell types such as differentiation, cell-cycle switching, migration, symmetry breaking, nurse-cell engulfment, egg-shell formation, and corpus luteum signaling. Extensive experimental validation of unique expression patterns in both ovarian and nearby, nonovarian cells also led to the identification of many new cell type-and stage-specific markers. The inclusion of several nearby tissue types in this data set also led to our identification of functional convergence in expression between distantly related cell types such as the immune-related genes that were similarly expressed in immune cells (hemocytes) and ovarian somatic cells (stretched cells) during their brief phagocytic role in nurse-cell engulfment. Taken together, these findings provide new insight into the temporal regulation of genes in a cell-type specific manner during oogenesis and begin to reveal the relatedness in expression between cell and tissues types.


Assuntos
Drosophila melanogaster/citologia , Oogênese/genética , Ovário/citologia , Animais , Animais Geneticamente Modificados , Diferenciação Celular/genética , Linhagem da Célula , Drosophila melanogaster/genética , Feminino , Perfilação da Expressão Gênica , Marcadores Genéticos , Hemócitos/citologia , Hemócitos/fisiologia , Mitose/genética , Folículo Ovariano/citologia , Ovário/fisiologia , Ovulação/genética , Análise de Sequência de RNA , Análise de Célula Única/métodos
12.
Ann Endocrinol (Paris) ; 81(2-3): 83-88, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32340851

RESUMO

Gonad differentiation depends on a set of cellular and hormonal signals interacting in a specific order, with very precise windows of action, to contribute to the establishment of the genital tract and a male or female phenotype. Research initially focused on the stages of gonad differentiation toward testis, in particular following the identification in 1990 of the SRY factor on chromosome Y. The mechanisms involved in gonad differentiation toward ovary took longer to identify. Thanks to patients with different sexual development (DSD) and animal knock-out models, description of the cascades involved in the activation and maintenance of ovarian development has progressed considerably in recent years.


Assuntos
Gônadas/fisiologia , Ovário/fisiologia , Processos de Determinação Sexual/fisiologia , Diferenciação Sexual/genética , Animais , Diferenciação Celular/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Gônadas/embriologia , Gônadas/crescimento & desenvolvimento , Humanos , Masculino , Ovário/embriologia , Ovário/crescimento & desenvolvimento , Fenótipo , Desenvolvimento Sexual/genética , Desenvolvimento Sexual/fisiologia
13.
Cell Physiol Biochem ; 54(3): 417-437, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32348667

RESUMO

BACKGROUND/AIMS: Obesity is associated with infertility, decreased ovarian performance and lipotoxicity. However, little is known about the aetiology of these reproductive impairments. Here, we hypothesise that the majority of changes in ovarian physiology in diet-induced obesity (DIO) are a consequence of transcriptional changes downstream of altered leptin signalling. Therefore, we investigated the extent to which leptin signalling is altered in the ovary upon obesity with particular emphasis on effects on cumulus cells (CCs), the intimate functional companions of the oocyte. Furthermore, we used the pharmacological hyperleptinemic (LEPT) mouse model to compare transcriptional profiles to DIO. METHODS: Mice were subjected to DIO for 4 and 16 weeks (wk) and leptin treatment for 16 days, to study effects in the ovary in components of leptin signalling at the transcript and protein levels, using Western blot, Real-time PCR and immunostaining. Furthermore, we used low-cell RNA sequencing to characterise changes in the transcriptome of CCs in these models. RESULTS: In the DIO model, obesity led to establishment of ovarian leptin resistance after 16 wk high fat diet (HFD), as evidenced by increases in the feedback regulator suppressor of cytokine signalling 3 (SOCS3) and decreases in the positive effectors phosphorylation of tyrosine 985 of leptin receptor (ObRb-pTyr985) and Janus kinase 2 (pJAK2). Transcriptome analysis of the CCs revealed a complex response to DIO, with large numbers and distinct sets of genes deregulated at early and late stages of obesity; in addition, there was a striking correlation between body weight and global transcriptome profile of CCs. Further analysis indicated that the transcriptome profile in 4 wk HFD CCs resembled that of LEPT CCs, in the upregulation of cellular trafficking and impairment in cytoskeleton organisation. Conversely, after 16 wk HFD CCs showed expression changes indicative of augmented inflammatory responses, cell morphogenesis, and decreased metabolism and transport, mainly as a consequence of the physiological changes of obesity. CONCLUSION: Obesity leads to ovarian leptin resistance and major time-dependent changes in gene expression in CCs, which in early obesity may be caused by increased leptin signalling in the ovary, whereas in late obesity are likely to be a consequence of metabolic changes taking place in the obese mother.


Assuntos
Células do Cúmulo/metabolismo , Leptina/farmacologia , Obesidade/metabolismo , Oócitos/metabolismo , Ovário/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica/fisiologia , Inflamação/metabolismo , Janus Quinase 2/metabolismo , Leptina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/genética , Ovário/fisiologia , Fosforilação , RNA-Seq , Receptores para Leptina/metabolismo , Transdução de Sinais/fisiologia , Proteína 3 Supressora da Sinalização de Citocinas/genética
15.
BMC Res Notes ; 13(1): 81, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32075679

RESUMO

OBJECTIVES: Culiseta longiareolata is a cosmopolitan species and has implicated in the transmission of avian malaria, tularemia, and arboviruses. Despite the wide distribution of Cs. longiareolata in Iran, little is known about its biology and physiology. The current research was conducted to study the autogeny behavior in this potential vector. During 2018, larvae and pupae were collected from Nazloo region in Urmia City using standard methods. Mosquitoes were reared in cages and fed by 5% sugar in laboratory conditions and were then dissected in phosphate-buffered saline (PBS) under a stereo microscope. RESULTS: In total, 230 adult female Cs. longiareolata mosquitoes were dissected. Egg rafts were observed in the ovary of only 10.86% unfed female mosquitoes. Autogeny behavior is a significant factor in the growth of population without a blood feeding. Therefore, it is necessary to study how autogenous reproduction affects mosquito-borne diseases.


Assuntos
Culicidae/fisiologia , Laboratórios , Animais , Feminino , Irã (Geográfico) , Ovário/fisiologia , Óvulo/fisiologia , Reprodução
16.
J Ovarian Res ; 13(1): 12, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32014030

RESUMO

BACKGROUND: Degeneration of ovarian function is an obvious feature of female aging. In addition, studies have shown that autophagy decreases with age, and DNA methylation is a hallmark epigenetic pattern during aging. However, it is not clear whether the expression and DNA methylation of autophagy genes are involved in the declines in ovarian function that occur during aging. RESULTS: Three groups of rats were used: 6-month-old (6 M) rats, 12-month-old (12 M) rats and 24-month-old (24 M) rats. Serum E2 levels and the mRNA and protein expression levels of Atg5, Atg12, Atg16L, Beclin1 and Lc3B were significantly decreased in aged rats. In addition, the methylation levels of the Atg5 gene were significantly increased in aged rats. The expression of the Dnmt1 and Dnmt2 genes decreased with aging; however, the expression of the Dnmt3A and Dnmt3B genes gradually increased with aging. CONCLUSIONS: Decreased autophagic activity was involved in the declines in ovarian function in aging rats. Upregulation of the DNA methyltransferases Dnmt3A and Dnmt3B may have led to methylation of the autophagy genes Atg5 and Lc3B to ultimately cause the observed decreases in autophagic activity.


Assuntos
Metilação de DNA , Ovário/fisiologia , Envelhecimento/fisiologia , Animais , Autofagia/genética , Feminino , Ratos
17.
Poult Sci ; 99(2): 1163-1173, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32029148

RESUMO

Variation in egg production exists in commercial turkey hens, with low egg producing hens (LEPH) costing more per egg produced than high egg producing hens (HEPH). Egg production correlates with ovulation frequency, which is governed by the hypothalamic-pituitary-gonadal (HPG) axis. Ovulation is stimulated by a preovulatory surge (PS) of progesterone and luteinizing hormone, triggered by gonadotropin releasing hormone release and inhibited by gonadotropin inhibiting hormone. Differences between LEPH and HEPH were characterized by determining HPG axis plasma hormone profiles and mRNA levels for key genes, both outside and inside of the PS (n = 3 per group). Data were analyzed with a 2-way ANOVA using the mixed models procedure of SAS. In the HPG axis, plasma progesterone levels were not affected by egg production level but were elevated during the PS. In contrast, plasma estradiol levels were higher in HEPH than in LEPH but were not associated with the PS. LEPH exhibited decreased gene expression associated with ovulation stimulation and increased gene expression associated with ovulation inhibition in the hypothalamus and pituitary. In ovarian follicle cells, LEPH displayed decreased gene expression associated with progesterone, androgen, and estradiol production in the F1 follicle granulosa cells, F5 theca interna cells, and small white follicle cells, respectively. Different degrees of stimulation and inhibition within all tissues of the HPG axis were noted between LEPH and HEPH turkey hens, with HEPH showing higher expression of genes related to ovulation and steroidogenesis.


Assuntos
Proteínas Aviárias/genética , Estradiol/sangue , Sistema Hipotálamo-Hipofisário/fisiologia , Ovário/fisiologia , Progesterona/sangue , Reprodução/fisiologia , Perus/fisiologia , Animais , Proteínas Aviárias/metabolismo , Feminino
18.
Reprod Biol Endocrinol ; 18(1): 11, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32070378

RESUMO

BRCA mutation carriers face various situations that influence their fertility potential. There is still a lack of guideline or expert consensus on Fertility Preservation (FP) in BRCA mutation carriers and the necessity and safety of FP in BRCA mutation carriers is still in dispute. This review aims to focus on the population of BRCA mutation carriers by analyzing the existing FP strategies, comprehensively comparing the pros and cons of each strategy and its applicability.FP is a suggestion for BRCA mutation carriers with birth planning. Different FP strategies have different characteristics. Considering the particularity of BRCA mutation carriers, multiple factors need to be carefully considered. This review focuses on the applicability of each FP method for carriers under various circumstances. Available FP strategies including oocyte cryopreservation, ovarian tissue cryopreservation, preimplantation genetic diagnosis, and egg/embryo donation are analyzed by comparing existing methods comprehensively. In the attempt to provide an up-to-date decision-making guidance. Conditions taking into consideration were the carrier's age, the risk of breast and ovarian metastasis, plans for oncotherapy, FP outcome, time available for FP intervention and accessibility.Overall, FP is necessary and safe for BRCA mutation carriers. Among all available FP methods, oocyte cryopreservation is the most reliable procedure; ovarian tissue cryopreservation is the only way for preserving both fertility and endocrine function, recommended for pre-pubertal carriers and when time is limited for oocyte stimulation. A clear framework provides frontline clinical practitioners a new thought and eventually benefit thousands of BRCA mutation carriers.


Assuntos
Proteína BRCA2/genética , Preservação da Fertilidade/métodos , Heterozigoto , Mutação/genética , Ovário/fisiologia , Ubiquitina-Proteína Ligases/genética , Criopreservação/métodos , Feminino , Humanos , Infertilidade Feminina/genética , Infertilidade Feminina/terapia , Recuperação de Oócitos/métodos , Gravidez
19.
Sci Rep ; 10(1): 1697, 2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-32015446

RESUMO

Gonads are the only edible part of the sea urchin and have great potential as a health-promoting food for human consumption. Polyunsaturated fatty acids (PUFAs) are important necessary nutrients that determine not only the nutritional value of sea urchins but guarantee their normal growth and reproduction. However, the information on the molecular mechanisms of PUFA biosynthesis and metabolism in this species remains elusive. In this study, we used Strongylocentrotus intermedius as our model species and conducted integrated metabolomic and transcriptomic analyses of potentially critical genes involved in PUFA biosynthesis and metabolism during gonad growth and development, mainly focusing on eicosapentaenoic acid (EPA). We found six differentially accumulated metabolites associated with PUFA in the metabolomic analysis. More differentially expressed genes (DEGs) were related to PUFA in testis than ovary (1823 DEGs in testis and 1499 DEGs in ovary). We verified 12 DEGs by RNA-Seq results and found that Aldh7a1, Ecm3, Fads2, and Hsd17b12 genes had similar expression patterns in EPA concentration during gonad growth and development. In contrast, the other DEGs were downregulated and we inferred that EPA or PUFA may be metabolized as energy during certain periods. Our metabolic and genetic data will facilitate a better understanding of PUFA regulation networks during gonad growth and development in S. intermedius.


Assuntos
Ácido Eicosapentaenoico/metabolismo , Metabolismo dos Lipídeos/genética , Ovário/fisiologia , Ouriços-do-Mar , Testículo/fisiologia , Animais , Ácido Eicosapentaenoico/biossíntese , Feminino , Perfilação da Expressão Gênica , Masculino , Metaboloma , Metabolômica , Transcriptoma
20.
Mar Biotechnol (NY) ; 22(2): 180-193, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32006128

RESUMO

In fish breeding practices, gamete maturity of females is vital to reproductive success. For some species, it is possible to estimate the female maturation status based on abdomen observation, but quite difficult for some species which mature at big size. To screen out the potential biomarker in fish blood relating to female maturation, we employed the approach integrating the UPLC-MS/MS and RNA-seq techniques to investigate the metabolites and genes reflecting the sexual maturation and spawning of female blunt snout bream Megalobrama amblycephala. The study included four groups, 1-year-old immature female individuals, 2-year-old immature female individuals, 2-year-old sexually mature female individuals, and 2-year-old sexually mature female individuals after 24 h of successful spawning. The upregulated metabolites in mature females were involved in "steroid hormone biosynthesis," "metabolic pathways," "glycerophospholipid metabolism," etc. compared with those of immature individuals. As the key intermediate of steroid hormone biosynthesis, 17α-hydroxypregnenolone exhibited the highest level in 2-year-old mature females than in the immature females. Meanwhile, the metabolites (i.e., dodecanoic acid and myristic acid) participating in fatty acid synthesis exhibited much lower levels in the females after spawning than those before spawning. In addition to the metabolites, the genes involved in ovarian steroidogenesis were significantly upregulated in the 2-year-old immature females compared to the 1-year-old immature females, indicating that the ovarian steroidogenesis plays important roles in ovarian development of M. amblycephala at the early stages. The significant upregulation of genes (i.e., itpr1, camk2, and mekk2) involved in the "GnRH signaling pathway" was observed in the mature females compared with the immature females, which indicated that the estrogen levels increased after female maturation in M. amblycephala. Moreover, many genes (e.g., gck, creb1, tf2-9, ryr2, asgr1, and creb1) regulating insulin secretion and thyroid hormone synthesis were significantly downregulated after female spawning. The dynamics of gene expression and metabolites observed in this study provide novel cues for guiding fish practical artificial reproduction.


Assuntos
Biomarcadores/sangue , Cyprinidae/fisiologia , Maturidade Sexual/fisiologia , Animais , Cyprinidae/sangue , Cyprinidae/genética , Ácidos Graxos/biossíntese , Feminino , Hormônios Esteroides Gonadais/biossíntese , Metaboloma , Ovário/fisiologia , Transdução de Sinais/genética , Transcriptoma
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