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1.
Am J Physiol Cell Physiol ; 319(2): C359-C370, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32520610

RESUMO

SLC4A11 is the only member of the SLC4 family that transports protons rather than bicarbonate. SLC4A11 is expressed in corneal endothelial cells, and its mutation causes corneal endothelial dystrophy, although the mechanism of pathogenesis is unknown. We previously demonstrated that the magnitude of the H+ conductance (Gm) mediated by SLC4A11 is increased by rises in intracellular as well as extracellular pH (pHi and pHe). To better understand this feature and whether it is altered in disease, we studied the pH dependence of wild-type and mutant mouse Slc4a11 expressed in Xenopus oocytes. Using voltage-clamp circuitry in conjunction with a H+-selective microelectrode and a microinjector loaded with NaHCO3, we caused incremental rises in oocyte pHi and measured the effect on Gm. We find that the rise of Gm has a steeper pHi dependence at pHe =8.50 than at pHe =7.50. Data gathered at pHe =8.50 can be fit to the Hill equation enabling the calculation of a pK value that reports pHi dependence. We find that mutation of lysine residues that are close to the first transmembrane span (TM1) causes an alkaline shift in pK. Furthermore, two corneal-dystrophy-causing mutations close to the extracellular end of TM1, E399K and T401K (E368K and T370K in mouse), cause an acidic shift in pK, while a third mutation in the fourth intracellular loop, R804H (R774H in mouse), causes an alkaline shift in pK. This is the first description of determinants of SLC4A11 pH dependence and the first indication that a shift in pH dependence could modify disease expressivity in some cases of corneal dystrophy.


Assuntos
Proteínas de Transporte de Ânions/genética , Transporte Biológico/genética , Distrofias Hereditárias da Córnea/genética , Lisina/genética , Simportadores/genética , Animais , Animais Geneticamente Modificados/genética , Animais Geneticamente Modificados/metabolismo , Bicarbonatos/metabolismo , Distrofias Hereditárias da Córnea/metabolismo , Distrofias Hereditárias da Córnea/patologia , Modelos Animais de Doenças , Epitélio Posterior/metabolismo , Epitélio Posterior/patologia , Regulação da Expressão Gênica/genética , Células HEK293 , Humanos , Concentração de Íons de Hidrogênio , Transporte de Íons/genética , Lisina/metabolismo , Camundongos , Mutação/genética , Oócitos/metabolismo , Oócitos/patologia , Sódio , Xenopus/genética
2.
Ecotoxicol Environ Saf ; 201: 110826, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32521368

RESUMO

As an effective feed additive in the livestock industry, olaquindox (OLA) has been widely used in domestic animal production. However, it is unclear whether OLA has negative effects on mammalian oocyte quality and fetal development. In this study, toxic effects of OLA were tested by intragastric gavage ICR mice with water, low-dose OLA (5 mg/kg/day), or high-dose OLA (60 mg/kg/day) for continuous 45 days. Results showed that high-dose OLA gavage severely affected the offspring birth and growth. Significantly, high-dose OLA impaired oocyte maturation and early embryo development, indicated by the decreased percentage of germinal vesicle breakdown, first polar body extrusion and blastocyst formation. Meanwhile, oxidative stress levels were increased in oocytes or ovaries, indexed by the increased levels of ROS, MDA, H2O2, NO, and decreased levels of GSH, SOD, CAT, GSH-Px and GSH-Rd. Furthermore, aberrant mitochondria distribution, defective spindle assembly, abnormal H3K4me2/H3K9me3 levels, increased DNA double-strand breaks and early apoptosis rate, were observed after high-dose OLA gavage. Taken together, our results for the first time illustrated that high-dose OLA gavage led to sub-fertility of females, which means that restricted utilization of OLA as feed additive should be considered.


Assuntos
Desenvolvimento Embrionário/efeitos dos fármacos , Aditivos Alimentares/toxicidade , Oócitos/efeitos dos fármacos , Oogênese/efeitos dos fármacos , Quinoxalinas/toxicidade , Administração Oral , Animais , Apoptose/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Peróxido de Hidrogênio/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Mitocôndrias/efeitos dos fármacos , Oócitos/metabolismo , Oócitos/patologia , Ovário/efeitos dos fármacos , Ovário/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos
3.
Am J Hum Genet ; 107(1): 15-23, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32473092

RESUMO

Normal oocyte meiosis is a prerequisite for successful human reproduction, and abnormalities in the process will result in infertility. In 2016, we identified mutations in TUBB8 as responsible for human oocyte meiotic arrest. However, the underlying genetic factors for most affected individuals remain unknown. TRIP13, encoding an AAA-ATPase, is a key component of the spindle assembly checkpoint, and recurrent homozygous nonsense variants and a splicing variant in TRIP13 are reported to cause Wilms tumors in children. In this study, we identified homozygous and compound heterozygous missense pathogenic variants in TRIP13 responsible for female infertility mainly characterized by oocyte meiotic arrest in five individuals from four independent families. Individuals from three families suffered from oocyte maturation arrest, whereas the individual from the fourth family had abnormal zygote cleavage. All displayed only the infertility phenotype without Wilms tumors or any other abnormalities. In vitro and in vivo studies showed that the identified variants reduced the protein abundance of TRIP13 and caused its downstream molecule, HORMAD2, to accumulate in HeLa cells and in proband-derived lymphoblastoid cells. The chromosome mis-segregation assay showed that variants did not have any effects on mitosis. Injecting TRIP13 cRNA into oocytes from one affected individual was able to rescue the phenotype, which has implications for future therapeutic treatments. This study reports pathogenic variants in TRIP13 responsible for oocyte meiotic arrest, and it highlights the pivotal but different roles of TRIP13 in meiosis and mitosis. These findings also indicate that different dosage effects of mutant TRIP13 might result in two distinct human diseases.


Assuntos
ATPases Associadas a Diversas Atividades Celulares/genética , Proteínas de Ciclo Celular/genética , Infertilidade Feminina/genética , Mutação de Sentido Incorreto/genética , Oócitos/patologia , Adulto , Alelos , Linhagem Celular Tumoral , Feminino , Células HeLa , Homozigoto , Humanos , Meiose/genética , Fenótipo , Zigoto/patologia
4.
Nat Commun ; 11(1): 1649, 2020 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-32245998

RESUMO

Human and mouse oocytes' developmental potential can be predicted by their mechanical properties. Their development into blastocysts requires a specific stiffness window. In this study, we combine live-cell and computational imaging, laser ablation, and biophysical measurements to investigate how deregulation of cortex tension in the oocyte contributes to early developmental failure. We focus on extra-soft cells, the most common defect in a natural population. Using two independent tools to artificially decrease cortical tension, we show that chromosome alignment is impaired in extra-soft mouse oocytes, despite normal spindle morphogenesis and dynamics, inducing aneuploidy. The main cause is a cytoplasmic increase in myosin-II activity that could sterically hinder chromosome capture. We describe here an original mode of generation of aneuploidies that could be very common in oocytes and could contribute to the high aneuploidy rate observed during female meiosis, a leading cause of infertility and congenital disorders.


Assuntos
Aneuploidia , Proteínas do Citoesqueleto/metabolismo , Miosina Tipo II/metabolismo , Oócitos/patologia , Animais , Segregação de Cromossomos , Feminino , Infertilidade/etiologia , Meiose , Camundongos , Oogênese
5.
Biomed Res Int ; 2020: 6279795, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32104701

RESUMO

This review analyses the genetic mechanisms of acephalic spermatozoa (AS) defects, which are associated with primary infertility in men. Several target genes of headless sperms have been identified but intracytoplasmic sperm injection (ICSI) outcomes are complex. Based on electron microscopic observations, broken points of the sperm neck are AS defects that are based on various genes that can be classified into three subtypes: HOOK1, SUN5, and PMFBP1 genes of subtype II; TSGA10 and BRDT genes of subgroup III, while the genetic mechanism(s) and aetiology of AS defects of subtype I have not been described and remain to be explored. Interestingly, all AS sperm of subtype II achieved better ICSI outcomes than other subtypes, resulting in clinical pregnancies and live births. For subtype III, the failure of clinical pregnancy can be explained by the defects of paternal centrioles that arrest embryonic development; for subtype I, this was due to a lack of a distal centriole. Consequently, the embryo quality and potential ICSI results of AS defects can be predicted by the subtypes of AS defects. However, this conclusion with regard to ICSI outcomes based on subtypes still needs further research, while the existence of quality of oocyte and implantation failure in women cannot be ignored.


Assuntos
Infertilidade Masculina/genética , Oócitos/metabolismo , Espermatozoides/patologia , Adulto , Implantação do Embrião/genética , Implantação do Embrião/fisiologia , Feminino , Humanos , Infertilidade Masculina/patologia , Masculino , Proteínas de Membrana/genética , Proteínas Associadas aos Microtúbulos/genética , Oócitos/crescimento & desenvolvimento , Oócitos/patologia , Gravidez , Taxa de Gravidez , Espermatozoides/crescimento & desenvolvimento
6.
Environ Mol Mutagen ; 61(4): 433-444, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31922297

RESUMO

As a member of parabens (PBs), Isobutylparaben (IBP) has a broad-spectrum antimicrobial activity and widely used in personal care products and cosmetics. Recent studies have indicated that usage of IBP poses a potential threat to reproductive health. In this study, we aimed to reveal the effects of acute exposure to IBP on the meiotic maturation of porcine cumulus oocyte complexes. Initial study showed that 200 µM of IBP significantly reduced the rate of the first polar body extrusion with no significant effect on cumulus cell expansion; however, 400 µM of IBP could significantly affect both. Further research revealed that abnormal spindles, misalignment chromosomes, and aberrant distributed actin filaments were detected in IBP-treated oocytes, which indicates that the cytoskeleton architecture of oocyte could be the target of IBP. At the same time, ROS level and apoptosis rate of oocyte were significantly increased by IBP exposure. Moreover, the levels of H3K9me3 and H3K27me3 were significantly induced in oocytes by IBP. Collectively, these results demonstrate that acute exposure to IBP could disrupt porcine oocyte maturation through affecting cytoskeleton, oxidative stress, viability and epigenetic modification. Environ. Mol. Mutagen. 2020. © 2020 Wiley Periodicals, Inc.


Assuntos
Anti-Infecciosos/efeitos adversos , Citoesqueleto/efeitos dos fármacos , Oócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Parabenos/efeitos adversos , Animais , Células Cultivadas , Citoesqueleto/metabolismo , Citoesqueleto/patologia , Feminino , Técnicas de Maturação in Vitro de Oócitos , Oócitos/citologia , Oócitos/patologia , Suínos
7.
Mycotoxin Res ; 36(1): 93-101, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31473931

RESUMO

Alternariol (AOH) is produced by fungi of the genus Alternaria and can be found in fruits, vegetables, and grains. Besides the oestrogenic activity demonstrated in vitro, this mycotoxin causes DNA damage and cell cycle arrest. Based on this, the effect of AOH was investigated on porcine female gametes during in vitro maturation and subsequent initial embryo development. A first experiment assessed a dose-response effect of AOH (5, 10, or 20 µmol/l) on cumulus expansion and in vitro oocyte nuclear maturation, in the presence or absence of follicular fluid (FF). A second experiment evaluated the effect of AOH (5, 10, or 20 µmol/l) exposure during porcine oocyte maturation, initial embryo development, or both periods, on preimplantation embryo development. Although FF protected oocytes from the deleterious effect of AOH, it did not avoid a decrease in cumulus cells expansion (5 µmol/l AOH regardless of the presence of FF). Moreover, exposure to AOH resulted in the degeneration of oocytes (10 µmol/l AOH in the absence of FF) and the occurrence of nuclear aberrations in mature oocytes (10 µmol/l AOH in the absence of FF and 20 µmol/l AOH in the presence of FF). Exposure to 5 µmol/l AOH during oocyte in vitro maturation was sufficient to impair initial embryo development.


Assuntos
Desenvolvimento Embrionário/efeitos dos fármacos , Lactonas/toxicidade , Oócitos/efeitos dos fármacos , Alternaria/metabolismo , Animais , Feminino , Líquido Folicular , Micotoxinas/toxicidade , Oócitos/patologia , Gravidez , Suínos
8.
Environ Toxicol ; 35(2): 152-158, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31696613

RESUMO

Fluorene-9-bisphenol (9,9-bis(4-hydroxyphenyl)-fluorene [BHPF]) is a bisphenol A (BPA) substitute used in the production of "BPA-free" plastics, now has been identified is harmful to living organisms. Our previous study showed that BHPF impaired mouse denuded oocyte in vitro maturation. However, there is a question that whether BHPF is still able to affect oocyte maturation in the presence of dense cumulus cells. In the present study, we checked the toxic effects of BHPF on porcine oocyte maturation which is derived from COCs in vitro culture. Our results showed that BHPF (50 µM) inhibited the expansion of cumulus cells, led to a significant decrease in polar body extrusion (PBE). Importantly, BHPF resulted in abnormal spindle assembly, ATP level decrease, reactive oxygen species (ROS) accumulation and early apoptosis in porcine oocytes, which are all negative to oocyte maturation. Furthermore, BHPF also declined porcine oocyte quality by disturbing the cortical granules (CGs) distribution. In conclusion, our study showed that BHPF still inhibited oocyte maturation even in the presence of cumulus cells leading to abnormal spindle assembly, ATP decrease, increased ROS level, early apoptosis, and disturbed CGs distribution in porcine oocytes, and also indicates that BHPF has a wide range toxic effects on oocyte in different species.


Assuntos
Apoptose/efeitos dos fármacos , Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Oócitos/efeitos dos fármacos , Oogênese/efeitos dos fármacos , Fenóis/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Animais , Feminino , Técnicas de Maturação in Vitro de Oócitos , Camundongos , Oócitos/crescimento & desenvolvimento , Oócitos/metabolismo , Oócitos/patologia , Suínos
9.
Environ Pollut ; 256: 113374, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31672358

RESUMO

Melatonin is a hormone which is generated from pineal gland, and it is responsible for the regulation of wake-sleep cycle. Melatonin is a well-known antioxidant and free radical scavenger to protect against multiple type of tissue damage. While ochratoxin A (OTA) is a mycotoxin found widely in contaminated food and foodstuffs, which causes nephrotoxicity, hepatotoxicity, immunotoxicity, and reproductive damage in humans and animals. In present study we report the toxicity of OTA on porcine oocyte quality and the protective effects of melatonin on OTA-exposed oocytes. Using transcriptome analysis our results show that OTA exposure alters the expression of multiple genes in oocytes, indicating its effect on oocyte maturation. The cellular changes following OTA treatment are examined, and the results show that OTA adversely affects oocyte polar body extrusion, which is confirmed by the delay of Cdc2-mediated cell cycle progression. OTA exposure also disrupts meiotic spindle formation, which is confirmed by altered phosphorylated MAPK expression. RNA-seq screening and further fluorescence staining results show that OTA induces aberrant mitochondria distribution and oxidative phosphorylation defects, which then causes oxidative stress, followed by early apoptosis and autophagy. Treatment with melatonin significantly ameliorates oxidative stress and apoptosis, which further protects cell cycle and spindle formation in OTA-exposed oocytes. Collectively, these results show the protective effects of melatonin against defects induced by OTA during porcine meiotic oocyte maturation.


Assuntos
Apoptose/efeitos dos fármacos , Melatonina/farmacologia , Ocratoxinas/toxicidade , Oócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Suínos , Animais , Antioxidantes/metabolismo , Autofagia/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Feminino , Humanos , Oócitos/metabolismo , Oócitos/patologia
10.
Theriogenology ; 142: 296-302, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31708194

RESUMO

Environmental stresses, such as heat stress (HS), have been shown to have diverse effects on the developmental competence of oocytes. The aim of this study was to determine the effect of exogenous conjugated linoleic acid (CLA) supplementation in maturation medium on bovine oocyte maturation and developmental competence under HS condition. Accordingly, cumulus-oocyte complexes (COCs) were cultured at 41 °C and 38.5 °C for the first and second 12 h of maturation in the presence of 0 (PC), 50 (CLA50-HS) and 100 (CLA100-HS) µM CLA. Also, a group of COCs were cultured at 38.5 °C for 24 h of maturation without CLA supplementation as negative control (NC). Nuclear maturation, level of intracellular glutathione (GSH), reactive oxygen species (ROS) content, cleavage and blastocyst rates as well as relative expression of BAX, and BCL2 genes in blastocysts were investigated. Our finding for the PC and NC groups revealed that HS decreased the percentage of MII oocytes, cleavage and blastocyst rates (P < 0.05). Moreover, HS lead to an increase in ROS levels and relative expression of BAX gene, decreased the intracellular content of GSH and relative expression of BCL2 gene (P < 0.05). However, the cleavage and blastocyst rates tended to increase in the CLA-supplemented groups compared to PC group (p < 0.10). Also, ROS and GSH levels in the matured oocytes decreased and increased in the CLA50-HS group compared to the PC group (P < 0.05), respectively. The ratio of expression levels of BAX to BCL2 genes was not different between the PC and CLA50-HS groups (P > 0.05). These findings suggest that HS has undesirable effects on the maturation competence of bovine oocyte and subsequent embryo development while administration of CLA can ameliorate some of adverse effects of HS.


Assuntos
Desenvolvimento Embrionário/efeitos dos fármacos , Transtornos de Estresse por Calor/patologia , Técnicas de Maturação in Vitro de Oócitos/métodos , Ácidos Linoleicos Conjugados/farmacologia , Oócitos/efeitos dos fármacos , Oogênese/efeitos dos fármacos , Animais , Bovinos , Células Cultivadas , Meios de Cultura/química , Meios de Cultura/farmacologia , Feminino , Fertilização In Vitro , Glutationa/metabolismo , Transtornos de Estresse por Calor/metabolismo , Transtornos de Estresse por Calor/veterinária , Resposta ao Choque Térmico/fisiologia , Técnicas de Maturação in Vitro de Oócitos/veterinária , Oócitos/patologia , Oócitos/fisiologia , Espécies Reativas de Oxigênio/metabolismo
11.
J Assist Reprod Genet ; 36(12): 2593-2604, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31760547

RESUMO

PURPOSE: Women with early-stage breast cancer may still have a future child wish, while chemotherapy may impair fertility. To pursue on fertility preservation shortly after breast cancer diagnosis is complex. This review holds a critical reflection on all topics that need to be counseled to give them the opportunity to make a well-informed decision before starting any oncological treatment. METHODS: A comprehensive literature review was performed on papers published in English language on breast cancer in young women, risk of chemotherapy-induced infertility, fertility preservation techniques, impact of possible mutation carriership, and future pregnancy outcome. RESULTS: Below 40 years of age, the risk of permanent chemotherapy-induced ovarian function failure is approximately 20%, where taxanes do not significantly add to this risk. Overall, 23% of reported women who performed fertility preservation by cryopreserving oocytes or embryos returned for embryo transfer. Of these, 40% gave live birth. Both fertility preservation in women diagnosed with breast cancer and pregnancy after treatment seem safe with respect to breast cancer survival. Women who have a genetic predisposition for breast cancer like BRCA gene mutation should also be informed about the possibility of pre-implantation genetic diagnosis. CONCLUSIONS: Women with an early stage of breast cancer and a possible future child wish should be referred to an expertise center in breast cancer, fertility preservation, and genetics in this complex decision-making process, shortly after diagnosis.


Assuntos
Neoplasias da Mama/diagnóstico , Detecção Precoce de Câncer , Aconselhamento Genético , Infertilidade Feminina/fisiopatologia , Adulto , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Criança , Criopreservação , Feminino , Fertilidade/efeitos dos fármacos , Fertilidade/fisiologia , Preservação da Fertilidade/métodos , Humanos , Infertilidade Feminina/patologia , Infertilidade Feminina/prevenção & controle , Recuperação de Oócitos/métodos , Oócitos/crescimento & desenvolvimento , Oócitos/patologia , Indução da Ovulação/métodos , Gravidez , Taxoides/uso terapêutico , Adulto Jovem
12.
J Assist Reprod Genet ; 36(12): 2403-2418, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31705227

RESUMO

PURPOSE: Molecular cytogenetic analysis has confirmed that a proportion of apparently meiotic aneuploidy may be present in the germ cells prior to the onset of meiosis, but there is no clear perception of its frequency. The aim of this review is to assess the evidence for premeiotic aneuploidy from a variety of sources to arrive at an estimate of its overall contribution to oocyte aneuploidy in humans. METHODS: Relevant scientific literature was covered from 1985 to 2018 by searching PubMed databases with search terms: gonadal/germinal mosaicism, ovarian mosaicism, premeiotic aneuploidy, meiosis and trisomy 21. Additionally, a key reference from 1966 was included. RESULTS: Data from over 9000 cases of Down syndrome showed a bimodal maternal age distribution curve, indicating two overlapping distributions. One of these matched the pattern for the control population, with a peak at about 28 years and included all cases that had occurred independently of maternal age, including those due to germinal mosaicism, about 40% of the cohort. The first cytological proof of germinal mosaicism was obtained by fluorescence in situ hybridisation analysis. Comparative genomic hybridisation analysis of oocyte chromosomes suggests an incidence of up to 15% in premeiotic oocytes. Direct investigation of fetal ovarian cells led to variable results for chromosome 21 mosaicism. CONCLUSIONS: Oocytes with premeiotic errors will significantly contribute to the high level of preimplantation and prenatal death. Data so far available suggests that, depending upon the maternal age, up to 40% of aneuploidy that is present in oocytes at the end of meiosis I may be due to germinal mosaicism.


Assuntos
Aneuploidia , Cromossomos/genética , Meiose/genética , Mosaicismo , Hibridização Genômica Comparativa , Feminino , Células Germinativas/crescimento & desenvolvimento , Células Germinativas/patologia , Humanos , Idade Materna , Oócitos/crescimento & desenvolvimento , Oócitos/patologia , Gravidez
13.
J Med Case Rep ; 13(1): 325, 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31676009

RESUMO

BACKGROUND: Oculocerebrorenal syndrome of Lowe is an X-linked disorder with very low prevalence in the general population. The OCRL gene encodes the protein phosphatidylinositol 4,5-bisphosphate-5-phosphatase, a lipid phosphatase, located in the trans-Golgi network. Point mutations in the OCRL gene cause Lowe syndrome and Dent disease, which are characterized as a multisystemic disorder. The symptoms of Lowe syndrome are expressed primarily as dysfunction of the eyes, kidneys, and the central nervous system. CASE PRESENTATION: This report describes a case of a 31-year-old Georgian woman with a de novo pathogenic mutation causing oculocerebrorenal syndrome of Lowe, who was a volunteer in an oocyte donation program for in vitro fertilization purposes, and the outcome of the treatments of this particular donor's oocyte receivers, describing the implications of the mutation for the children born as a result of the treatments. It raises important medical and ethical issues about the necessity of genetic testing of oocyte donors and the possibility of rare genetic disorders being inherited by the offspring of donors. CONCLUSION: This particular case indicates the legal, medical, and emotional risks of utilizing donor oocytes from phenotypically healthy women, whose genetic constitution is unknown in terms of being silent carriers of rare diseases. In addition, all the necessary actions were followed; the further examinations that are required are mentioned. The donor and the offspring should be further tested. The remaining cryopreserved embryos should be destroyed or preimplantation genetic testing should be performed before they are utilized. Finally, all the people involved, the treated couples and the donor, alongside her family, should follow genetic and psychological counselling.


Assuntos
Heterozigoto , Síndrome Oculocerebrorrenal/genética , Doação de Oócitos , Oócitos/patologia , Adulto , Implantação do Embrião , Feminino , Aconselhamento Genético , Testes Genéticos , Humanos , Doação de Oócitos/psicologia , Gravidez
14.
PLoS One ; 14(10): e0222390, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31647816

RESUMO

The size of oocytes was previously reported to be smaller in obese women with polycystic ovary syndrome (PCOS). In the present prospective cohort study, we sought to determine whether oocyte size and morphology are associated with patient characteristics in non-PCOS women. Oocyte and oolemmal diameter were measured, enlarged perivitelline space (PVS) and ooplasmic granulation were assessed in 308 MII oocytes from 77 IVF/ICSI couples. Statistical analysis was undertaken using SAS version 9.4 (SAS institute Inc., USA). Continuous values are presented as mean ± SD and compared using a two-sample t-test or Mann-Whitney U test as appropriate. Categorical parameters are presented as proportions and compared using a Fisher exact test. Logistic and linear regression models were used to control for the effect of age for categorical and continuous variables respectively. P-value < 0.05 was considered statistically significant. Patients presented with a mean age of 40.3±5.0 years, had a BMI of 25.1±6.1 kg/m2, median AMH levels of 0.6 ng/ml and produced a median of 4 oocytes. Mean total oocyte diameter was 163.2±7.4 µm (range 145.8-182.1 µm), while oolemmal diameter was 109.4±4.1 µm (range 98.5-122.3 µm). After adjusting for age and ovarian reserve increasing BMI was associated with decreased total oocyte diameter (p<0.05). Total oocyte diameter was also inversely associated with AMH levels (p = 0.03) and oocyte yield (p = 0.04). In contrast to total oocyte diameter, oolemmal diameter was not related to patient characteristics. Younger women and those with large oocyte yields demonstrated fewer oocytes with ooplasmic granulation (p<0.05 and p = 0.01). After adjustments for age, ooplasmic granulation was also less frequently observed in oocytes from women with higher AMH (p = 0.03) and increasing BMI (p<0.01). Fertilization was more likely in oocytes with larger oolemmal diameter (p = 0.008). Embryos from oocytes with larger total and ooplasmic diameters were more likely to be transferred or frozen (p = 0.004 and p = 0.01). In non-PCOS infertile women, BMI and ovarian function relate to total oocyte diameter. These results expand on previously observed associations between oocyte size and BMI in women with PCOS. They indicate the importance of detailed oocyte assessments, which may aid the currently used criteria for embryo selection and help to better understand how oocyte status is associated with later embryo development.


Assuntos
Tamanho Celular , Infertilidade Feminina/terapia , Oócitos/crescimento & desenvolvimento , Reserva Ovariana/fisiologia , Adulto , Índice de Massa Corporal , Desenvolvimento Embrionário/fisiologia , Feminino , Fertilização In Vitro , Humanos , Infertilidade Feminina/fisiopatologia , Masculino , Pessoa de Meia-Idade , Recuperação de Oócitos/métodos , Oócitos/patologia , Indução da Ovulação , Síndrome do Ovário Policístico/patologia , Gravidez , Taxa de Gravidez , Injeções de Esperma Intracitoplásmicas
15.
Gynecol Endocrinol ; 35(sup1): 24-26, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31532315

RESUMO

The mechanisms of endometriosis-related infertility remain still unknown. Endometriosis and clinical markers of oocyte quality are a very important problem of reproduction. The purpose of the study is to assess the quality of oocytes in women with infertility associated with endometriosis. The study included infertile reproductive aged women, between 29 and 40 years who underwent IVF and ICSI procedures. The patients were divided into three groups: group I involved 50 (n = 50) patients with recurrent unilateral endometriomas, group II included 50 patients (n = 50) unilateral endometriomas after surgical treatment and control group with 30 (n = 30) patients with tubal factor infertility. Clinical and morphological assessment of oocyte quality was performed in all IVF/ICSI cycles. The results of the study demonstrate a statistically significant increase in the number of immature oocytes of metaphase MI and immature oocytes at the GV germinal vesicle stage in patients with infertility associated with endometriosis, compared with the control group (p<.005). There is deterioration in the quality of the obtained oocytes in patients with the presence of endometrioma more than 3 cm in diameter. The results of this study allow to conclude that endometriomas negatively affect quality of oocyte and ovarian reserve, whereas endometriomas after cystectomy, have a deleterious and sustained effect on ovarian reserve.


Assuntos
Endometriose/patologia , Infertilidade Feminina/patologia , Oócitos/patologia , Doenças Ovarianas/patologia , Adulto , Estudos de Casos e Controles , Células Cultivadas , Endometriose/complicações , Feminino , Fertilização In Vitro , Humanos , Técnicas de Maturação in Vitro de Oócitos , Infertilidade Feminina/etiologia , Metáfase/fisiologia , Recuperação de Oócitos , Doenças Ovarianas/complicações , Reserva Ovariana/fisiologia , Indução da Ovulação/métodos , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Injeções de Esperma Intracitoplásmicas
16.
Environ Pollut ; 255(Pt 1): 113194, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31520902

RESUMO

Heavy metal cadmium (Cd) is a widespread environmental contaminant with a potential toxicity that might adversely influence the health of experimental animals and humans. It has been known that Cd might accumulate in vertebrates for many years and thus leads to the hepatic and renal toxicity. Additionally, Cd concentration in the ovary increases with age and is highly related to the reproductive hazard. However, the underlying mechanisms regarding how Cd affects the female reproductive system especially the oocyte quality have not yet fully defined. Here, we reported that Cd exposure led to the defective nuclear maturation of oocytes via the impairment of cytoskeleton assembly, displaying the aberrant spindle organization, chromosome alignment and actin polymerization. In the meantime, Cd exposure caused the impaired cytoplasmic maturation by showing the disrupted dynamics of mitochondrial integrity and cortical granules, and thereby resulting in the compromised sperm binding ability and fertilization capacity of oocytes. More importantly, we found that glutathione (GSH) supplementation was able to recover the meiotic failure induced by Cd exposure through suppressing the excessive ROS level, DNA damage accumulation and apoptotic incidence. Taken together, our findings demonstrate that Cd exposure has the adverse effects on the oocyte meiotic maturation as well as subsequent fertilization, and provide a potential effective strategy to improve the quality of Cd-exposed oocytes.


Assuntos
Cádmio/toxicidade , Mitocôndrias/patologia , Oócitos/citologia , Oogênese/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Animais , Citoesqueleto/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Feminino , Glutationa/metabolismo , Humanos , Masculino , Meiose/efeitos dos fármacos , Oócitos/patologia , Suínos
17.
J Assist Reprod Genet ; 36(9): 1957-1962, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31428887

RESUMO

PURPOSE: To identify the disease-causing gene in a family with female infertility and fertilization failure. METHODS: Whole-exome sequencing and Sanger sequencing were used to identify the disease-causing gene in a female with infertility and fertilization failure. Subcellular localization and western blot analysis were used to check the effect of mutations. RESULTS: We identified novel compound heterozygous mutations c.598C>T (p.Arg200Ter) and c.1319G>C (p.Trp440Ser) in WEE2 gene in a female with infertility and fertilization failure. The p.Arg200Ter mutant WEE2 gene produce truncated protein and mainly located in the nucleus, the same as the wild protein, while the p.Trp440Ser mutant WEE2 proteins are located in the nucleus and cytoplasm and the expression level of p.Trp440Ser mutant WEE2 protein is reduced significantly compared with that of wild-type WEE2. CONCLUSIONS: We discovered novel compound heterozygous mutations c.598C>T (p.Arg200Ter) and c.1319G>C (p.Trp440Ser) in WEE2 gene in a female whose oocytes could not form pronucleus after intracytoplasmic sperm injection (ICSI). Moreover, mutations in WEE2 gene affect the normal function of WEE2 proteins and cause fertilization failure.


Assuntos
Proteínas de Ciclo Celular/genética , Infertilidade Feminina/genética , Proteínas Tirosina Quinases/genética , Adulto , Proteínas de Ciclo Celular/metabolismo , Feminino , Expressão Gênica , Células HEK293 , Células HeLa , Heterozigoto , Humanos , Infertilidade Feminina/patologia , Masculino , Mutação , Oócitos/patologia , Proteínas Tirosina Quinases/metabolismo , Injeções de Esperma Intracitoplásmicas , Falha de Tratamento , Sequenciamento Completo do Exoma
18.
J Assist Reprod Genet ; 36(10): 2067-2076, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31440957

RESUMO

PURPOSE: To evaluate whether ICSI offers any benefit compared with IVF in different ovarian response categories in case of non-male factor infertility. METHODS: This is a retrospective multicenter analysis using individual patient data, conducted in 15 tertiary referral hospitals in Europe (1 center in Belgium and 14 in Spain). The study included the first cycle of all patients undergoing ovarian stimulation for IVF or ICSI in a GnRH antagonist protocol. Only patients having either IVF or ICSI for non-male factor infertility were included. Patients were divided into 4 groups based on their ovarian response as follows: group A, poor responders (1-3 oocytes); group B, suboptimal responders (4-9 oocytes); group C, normal responders (10-15 oocytes); group D, high responders (> 15 oocytes). RESULTS: In total, 4891 patients were analyzed, of whom 4227 underwent ICSI and 664 IVF. There was no significant difference for the insemination method (ICSI vs. IVF) used among the different ovarian response categories: 87% vs. 13%, 87% vs. 13%, 86% vs. 14%, 84% vs. 16%, for groups A, B, C, and D, respectively, p value = 0.35. Mean fertilization rates and embryo utilization rates were comparable between IVF and ICSI in the whole cohort. Fresh and cumulative LBR did not differ significantly for IVF and ICSI in poor, suboptimal, normal, and high responders. CONCLUSION: There is no advantage of ICSI over IVF as insemination method for non-male factor infertility, irrespective of the ovarian response. The number of oocytes retrieved has no value for the selection of the insemination procedure in case of non-male infertility.


Assuntos
Fertilização In Vitro/métodos , Infertilidade/genética , Oócitos/crescimento & desenvolvimento , Injeções de Esperma Intracitoplásmicas/métodos , Adulto , Coeficiente de Natalidade , Europa (Continente)/epidemiologia , Feminino , Humanos , Infertilidade/fisiopatologia , Masculino , Recuperação de Oócitos/métodos , Oócitos/patologia , Ovário/crescimento & desenvolvimento , Ovário/metabolismo , Indução da Ovulação , Gravidez , Taxa de Gravidez , Espanha/epidemiologia
19.
Niger J Physiol Sci ; 34(1): 49-53, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31449271

RESUMO

Trypanosomosis has been described as the single largest disease entity limiting livestock development in sub-Saharan Africa. The effects on ovarian weight, follicle count and retrieved oocyte characteristics in ten West African dwarf goat does (control=5, infected=5) experimentally infected with Trypanosoma brucei were investigated. The does were fed with elephant grass and supplement (15.23% CP) daily. Infected does received 4.8x105 T. brucei intravenously and thereafter, all does were synchronized using Lutalyse®. The results showed that the differences between control and infected does for ovarian weight (0.68±0.56 g and 0.40±0.09 g) and follicle count (10.50±1.25 and 2.50±1.22),  respectively were significant (P<0.05). The difference in retrieved-oocytes-count between control (30, 57.7%) and infected (22, 42.3%)  does was not significant (P>0.05). The differences in proportion between control and infected does for well-formed-oocytes (90.5% and 9.5%), completely-denuded-oocytes (30.8% and 69.2%) and proportion per group of oocytes with substantial-investment-of-cumulus (63.3% and 9.1%), respectively were significant (P<0.05). The difference in extensively-denuded-oocytes between control (38.9%) and infected (61.1%) does was not significant (P>0.05). These findings suggest that experimental Trypanosoma brucei infection caused reduction in ovarian weight and follicle count, number of oocytes as well as proportion of well-formed oocytes that are capable of supporting embryonic development.


Assuntos
Recuperação de Oócitos/métodos , Oócitos/patologia , Folículo Ovariano/patologia , Trypanosoma brucei brucei , Tripanossomíase Africana/patologia , Animais , Feminino , Cabras , Nigéria , Tamanho do Órgão , Ovário/patologia , Gravidez
20.
J Pineal Res ; 67(4): e12603, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31370106

RESUMO

Mammalian oocytes remain arrested at the first prophase of meiosis in ovarian follicles for an extended period. During this protracted arrest, oocytes are remarkably susceptible to the accumulation of DNA damage. Melatonin (N-acetyl-5-methoxytryptamine), a hormone secreted by the pineal gland, has diverse effects on various physiological processes. However, the effect of melatonin on DNA damage response in mammalian oocytes has not been explored. Here, we showed that melatonin protected mouse oocytes from DNA damage induced by double-strand breaks (DSBs) during prophase arrest and subsequently improved oocyte quality. We found that DNA damage during prophase arrest impaired subsequent meiotic maturation and deteriorated oocyte quality, increasing chromosome fragmentation, spindle abnormality, mitochondrial aggregation, and oxidative stress. However, melatonin treatment during DNA damage accumulation at prophase improved meiotic maturation and relieved the quality decline of oocytes. In addition, melatonin inhibited the accumulation of DNA damage during prophase arrest by reducing the γ-H2AX levels. Although activated ATM levels were decreased by melatonin treatment, the effect of melatonin on DNA damage response was not a direct consequence of ATM inhibition. Instead, melatonin enhanced DNA repair via nonhomologous end-joining (NHEJ) pathway. Interestingly, these actions of melatonin on DNA damage response are receptor-independent in mouse oocytes. Therefore, our results demonstrated that melatonin protects oocytes from DNA damage during prophase arrest by enhancing DNA repair via NHEJ and subsequently prevents the deterioration of oocyte quality during meiotic maturation.


Assuntos
Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Reparo do DNA por Junção de Extremidades/efeitos dos fármacos , Melatonina/farmacologia , Oócitos/metabolismo , Animais , Feminino , Camundongos , Camundongos Endogâmicos ICR , Oócitos/patologia
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