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Frequent consumption of diet drinks was associated with oocyte dysmorphism, decreased embryo quality, and an adverse effect on pregnancy rate. We investigated the harmful effects of aspartame and potential mechanisms through which it increases infertility risk through clinical observations and in vivo and in vitro studies. Methods: We established a cohort of 840 pregnant women and retrospectively determined their time to conceive. We assessed the estrus cycle, the anti-Mullerian hormone level, ovarian oxidative stress, and ovarian mitochondrial function in an animal study. We also evaluated mitochondria function, mitochondrial biogenesis, and progesterone release with in vitro studies. Aspartame consumption was associated with increased infertility risk in the younger women (Odds ratio: 1.79, 95% confidence interval: 1.00, 3.22). The results of the in vivo study revealed that aspartame disrupted the estrus cycle and reduced the anti-Mullerian hormone level. Aspartame treatment also suppressed antioxidative activities and resulted in higher oxidative stress in the ovaries and granulosa cells. This phenomenon is caused by an aspartame-induced decline in mitochondrial function (maximal respiration, spare respiratory capacity, and ATP production capacity) and triggered mitochondrial biogenesis (assessed by examining the energy depletion signaling-related factors sirtuin-1, phosphorylated adenosine monophosphate-activated protein kinase, peroxisome proliferator-activated receptor-gamma coactivator-1α, and nuclear respiratory factor 1 expression levels). Aspartame may alter fertility by reserving fewer follicles in the ovary and disrupting steroidogenesis in granulosa cells. Hence, women preparing for pregnancy are suggested to reduce aspartame consumption and avoid oxidative stressors of the ovaries.
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Infertilidade , Doenças Mitocondriais , Animais , Feminino , Humanos , Gravidez , Aspartame , Hormônio Antimülleriano , Estudos RetrospectivosRESUMO
Endometriosis is an estrogen-dependent inflammatory disease that affects up to 10% of women of reproductive age and accounts for up to 50% of female infertility cases. It has been highly associated with poorer outcomes of assisted reproductive technology (ART), including decreased oocyte retrieval, lower implantation, and pregnancy rates. A better understanding of the pathogenesis of endometriosis-associated infertility is crucial for improving infertility treatment outcomes. Current theories regarding how endometriosis reduces fertility include anatomical distortion, ovulatory dysfunction, and niche inflammation-associated peritoneal or implantation defects. This review will survey the latest evidence on the role of inflammatory niche in the peritoneal cavity, ovaries, and uterus of endometriosis patients. Nonhormone treatment strategies that target these inflammation processes are also included. Furthermore, mesenchymal stem cell-based therapies are highlighted for potential endometriosis treatment because of their immunomodulatory effects and tropism toward inflamed lesion foci. Potential applications of stem cell therapy in treatment of endometriosis-associated infertility in particular for safety and efficacy are discussed.
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Endometriose/patologia , Infertilidade Feminina/etiologia , Endometriose/complicações , Endometriose/tratamento farmacológico , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Imunossupressores/uso terapêutico , Infertilidade Feminina/prevenção & controle , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Ovário/metabolismo , Ovário/patologia , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
PURPOSES: This study evaluated the effectiveness of cold-gel packing on episiotomy pain among postpartum women who had normal spontaneous deliveries. METHODS: A quasi-randomised control trial was conducted in a maternity ward of a regional teaching hospital in northern Taiwan. Seventy postpartum women were recruited, choosing to be in either the experimental or control group (35 women per group). Subjects in the experimental group received at least six interventions of cold-gel packing applied to the perineal wound and were provided oral analgesics routinely. The subjects in the control group received oral analgesics routinely. FINDINGS: Pain intensity, pain interference on daily activities and satisfaction levels with pain management were assessed using Brief Pain Inventory (BPI) and pain management questionnaire, respectively. The results showed that women in the experimental group reported significantly lower mean pain intensity score, pain interference on daily activities scores at 48 hours post-delivery, and higher level of satisfaction with pain management at 24 and 48 hours post-delivery than the control group after adjusting for demographic and obstetric data. CONCLUSIONS: Cold-gel packing on the perineum is a cost-effective, convenient, easy-to-deploy and non-pharmacologic approach to pain reduction, with an overall positive impact on postpartum recovery for parturients.
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Analgésicos/administração & dosagem , Crioterapia , Episiotomia/efeitos adversos , Manejo da Dor/métodos , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/terapia , Adulto , Feminino , Géis/uso terapêutico , Humanos , Períneo/cirurgia , Período Pós-Parto , Gravidez , TaiwanRESUMO
Introduction: Mifepristone-misoprostol treatment for medical abortion and miscarriage are safe and effective. This study aimed to assess clinical factors associated with subsequent surgical intervention after medical termination of early viable or non-viable pregnancy. Methods: This retrospective, single-center study included women who underwent medical abortion at Taipei Medical University between January 2010 and December 2019. A total of 1,561 subjects, with 1,080 viable and 481 non-viable pregnancies, who were treated with oral mifepristone 600 mg followed by misoprostol 600 mg 48 h later were included. Data of all pregnancies and medical termination of pregnancy were evaluated using regression analysis. The main outcome was successful termination of pregnancy. Results: The success rate of medical abortion was comparable in women with viable and non-viable (92.13% vs. 92.93%) pregnancies. Besides retained tissue, more existing pregnancies with ultrasonographic findings were found in the non-viable pregnancy group than in the viable pregnancy group (29.4% vs. 14.1%, p = 0.011). Multivariate analysis showed that previous delivery was an independent risk factor for failed medical abortion among all included cases. In women with viable pregnancy, longer gestational age [adjusted odds ratio (aOR): 1.483, 95% confidence interval (CI): 1.224-1.797, p < 0.001] and previous Cesarean delivery (aOR: 2.177, 95% CI: 1.167-40.62, p = 0.014) were independent risk factors for failed medical abortion. Number of Cesarean deliveries (aOR: 1.448, 95% CI: 1.029-2.039, p = 0.034) was an independent risk factor for failed medication abortion in women with non-viable pregnancies. Conclusion: This is the first cohort study to identify risk factors for subsequent surgical intervention in women with viable or non-viable pregnancies who had undergone early medically induced abortions. The success rate of medical abortion is comparable in women with viable and non-viable pregnancies. Previous delivery is an independent risk factor for failed medical abortion. Clinical follow-up may be necessary for women who are at risk of subsequent surgical intervention.
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BACKGROUND: In recent years, smart devices have become an integral part of daily life. However, longitudinal studies, particularly those regarding the relationship between toddlers' smart device usage and behavioral outcomes, are limited. Understanding the impact of parent-child interactions on this relationship is crucial for enhancing toddlers' developmental outcomes. Accordingly, this study examined the influence of early screen time and media content exposure on toddlers' behaviors, as well as the positive effects of mother-child interactions on this influence. METHODS: We used relevant data related to 277 children born between November 2016 and July 2020 and who were part of an ongoing prospective follow-up study conducted across five hospitals in Taipei City, Taiwan. We analyzed (1) data from maternal reports regarding children's behavior by using the Child Behavior Checklist (for ages 11/2-5 years), (2) assessments of mother-child interactions by using the Brigance Parent-Child Interactions Scale, and (3) self-reported parental data covering the first 3 postpartum years. Statistical analyses involved group-based trajectory modeling and multiple linear regression. RESULTS: A considerable increase in screen time between the ages of 1 and 3 years was associated with less favorable behavioral outcomes at age 3. These outcomes included somatic complaints [adjusted beta coefficient (aß) = 2.17, 95% confidence interval (CI) = 0.39-3.95, p-value = 0.01], withdrawal (aß = 2.42, 95% CI = 0.15-4.69, p-value = 0.04), and aggressive behavior (aß = 6.53, 95% CI = 0.25-12.81, p-value = 0.04). This association was particularly evident among children with lower levels of mother-child interaction. Nevertheless, positive mother-child interactions mitigated most of the adverse effects. Additionally, increased exposure to games and cartoons was associated with poorer behavioral outcomes in all children except for those experiencing positive mother-child interactions. CONCLUSION: Early mother-child interactions play a crucial role in mitigating the risk of behavioral problems in toddlers who spend prolonged periods looking at screens and who are frequently exposed to game and cartoon content.
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Hair cortisol concentration (HCC) is a valuable biomarker for evaluating chronic stress in preschoolers. However, few studies have explored early life HCC and its associated factors. This prospective cohort study analysed the HCC in children aged 6-48 months and its associations with parental HCC as well as positive and negative parental mental health outcomes. We used data from the ongoing Longitudinal Examination Across Prenatal and Postpartum Health in Taiwan (LEAPP-HIT) project, conducted in Taipei between 2020 and 2024. Hair samples were collected from both parents and children in 177 families (91 samples obtained during pregnancy and 86 during the postpartum period). The parents also completed self-reported questionnaires. Multiple linear regression was conducted to analyse the data. We observed a significant positive correlation between parents' and preschoolers' HCC. Furthermore, maternal depression (adjusted beta coefficient [aß] = 0.09, 95% confidence interval [CI] = 0.02, 0.16) and perceived stress (aß = 0.15, 95% CI = 0.02, 0.26) were positively associated with preschoolers' HCC. By contrast, higher maternal eudaimonia was associated with lower HCC in preschoolers (aß = -0.11, 95% CI = -0.20, -0.01). For parents, maternal depression, anxiety, and perceived stress were independently associated with an increased HCC during the postnatal period, whereas maternal eudaimonia was negatively associated with HCC. Our results indicate that both mothers and fathers affect children's responses to stress. Assessment of cortisol stress hormone concentrations through hair samples can be a key means of detecting preschoolers' stress levels and enabling early intervention.
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BACKGROUND: Although miscarriage and termination of pregnancy affect maternal mental illnesses on subsequent pregnancies, their effects on the positive mental health (e.g., eudaimonia) of both first-time and multi-time parents have received minimal attention, especially for fathers. This longitudinal study examines the effects of experiences of miscarriage and termination on parental well-being in subsequent pregnancies from prenatal to postpartum years, while simultaneously considering parity. METHODS: Pregnant women and their partners were recruited during early prenatal visits in Taiwan from 2011 to 2022 and were followed up from mid-pregnancy to 1 year postpartum. Six waves of self-reported assessments were employed. RESULTS: Of 1813 women, 11.3 % and 14.7 % had experiences of miscarriage and termination, respectively. Compared with the group without experiences of miscarriage or termination, experiences of miscarriage were associated with increased risks of paternal depression (adjusted odds ratio = 1.6, 95 % confidence interval [CI] = 1.13-2.27), higher levels of anxiety (adjusted ß = 1.83, 95 % CI = 0.21-3.46), and lower eudaimonia scores (adjusted ß = -1.09, 95 % CI = -1.99 to -0.19) from the prenatal to postpartum years, particularly among multiparous individuals. Additionally, experiences of termination were associated with increased risks of depression in their partner. LIMITATIONS: The experiences of miscarriage and TOP were self-reported and limited in acquiring more detailed information through questioning. CONCLUSIONS: These findings highlight the decreased well-being of men whose partners have undergone termination of pregnancy or experienced miscarriage, and stress the importance of interventions aimed at preventing adverse consequences among these individuals.
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Aborto Espontâneo , Masculino , Feminino , Gravidez , Humanos , Aborto Espontâneo/epidemiologia , Depressão/epidemiologia , Estudos Longitudinais , Ansiedade/epidemiologia , Pai/psicologiaRESUMO
OBJECTIVE: Recent clinical evidence has failed to demonstrate the benefits of elevation of serum high-density lipoprotein (HDL), suggesting potential loss of protective effects of HDL at high concentrations. This study aimed to investigate the concentration-related effects of HDL on in vitro and in vivo functions of human endothelial progenitor cells (EPCs) and related angiogenesis. METHODS AND RESULTS: Early and late outgrowth EPCs were generated from human circulating mononuclear cells. Oxidized low-density lipoprotein reduced viability of late outgrowth EPCs, which was reversed dose dependently by HDL. In the absence of oxidized low-density lipoprotein, HDL at low concentrations (5-50 µg/mL, equal to 0.5-5 mg/dL in human) enhanced EPC tube formation by activating phosphatidylinositol-3 kinase/Akt/endothelial NO synthase pathways. Moderate to high concentrations (400-800 µg/mL) of HDL paradoxically enhanced EPC senescence and impaired tube formation by activating Rho-associated kinase (ROCK) and inhibiting phosphatidylinositol-3 kinase/Akt and p38 mitogen-activated protein kinase pathways. Rho-associated kinase inhibitors, either Y27632 or statins, prevented high HDL-induced EPC senescence and improved in vitro tube formation, as well as in vivo capacity of angiogenesis of EPCs. CONCLUSIONS: While protecting EPCs from the injury of oxidized low-density lipoprotein, moderate to high concentrations of HDL paradoxically impaired EPCs and related angiogenesis in the absence of oxidized low-density lipoprotein by activating Rho-associated kinase pathways, providing mechanistic evidence of potential hazard effects of HDL.
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Endotélio Vascular/efeitos dos fármacos , Lipoproteínas HDL/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Quinases Associadas a rho/efeitos dos fármacos , Quinases Associadas a rho/fisiologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Senescência Celular/efeitos dos fármacos , Senescência Celular/fisiologia , Diabetes Mellitus/metabolismo , Diabetes Mellitus/fisiopatologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Endotélio Vascular/citologia , Humanos , Técnicas In Vitro , Lipoproteínas LDL/farmacologia , Masculino , Camundongos , Camundongos SCID , Neovascularização Fisiológica/fisiologia , Óxido Nítrico/metabolismo , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/fisiologia , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/fisiologia , Transdução de Sinais/fisiologia , Células-Tronco/citologia , Adulto Jovem , Proteínas Quinases p38 Ativadas por Mitógeno/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/fisiologiaRESUMO
BACKGROUND: Although studies have reported the effects of inadequate sleep on maternal health, few have examined the relationships of maternal sleep patterns with fetal health and early childhood development. This study investigated maternal sleep duration patterns from early pregnancy to 3-years postpartum and their effects on birth outcomes and child development. METHODS: This study recruited pregnant women and their partners during prenatal visits at five selected hospitals in the Taipei area; follow-up lasted from July 2011 to April 2021. A total of 1178 parents completed self-reported assessments from early pregnancy until childbirth and 544 completed eight assessments up to 3-years postpartum. Generalized estimated equation models were used for analyses. RESULTS: Group-based trajectory modeling was used to identify four trajectories of sleep duration patterns. Although maternal sleep duration was not associated with birth outcomes, maternal "short decreasing" and "stably short" sleep patterns were associated with a higher risk of suspected overall developmental delay and language developmental delay, respectively. Furthermore, an "extremely long decreasing" pattern was associated with a higher risk of suspected overall developmental delay, [adjusted odds ratio (aOR) = 2.97, 95% confidence interval (CI):1.39-6.36)], gross motor delay, (aOR = 3.14, 95% CI: 1.42-6.99) and language developmental delay (aOR = 4.59, 95% CI:1.62-13.00). The results were significant for the children of multiparous women. CONCLUSIONS: We identified a U-shaped distribution of risk between offspring developmental delay and maternal prenatal sleep duration, with the highest risk levels on both ends of the maternal prenatal sleep duration pattern. Interventions for maternal sleep are relatively straightforward to implement and should thus be a key part of standard prenatal care.
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Privação do Sono , Transtornos do Sono-Vigília , Feminino , Humanos , Pré-Escolar , Gravidez , Estudos Longitudinais , Privação do Sono/complicações , Gestantes , Desenvolvimento Infantil , SonoRESUMO
INTRODUCTION: Although mobile devices are used ubiquitously, studies on their detrimental effects on preschoolers are limited. Furthermore, no study has considered shared reading and mobile device usage simultaneously. Therefore, this study examined the effects of mobile devices and shared reading on preschoolers' development along with the effects of maternal depression on this association. MATERIALS AND METHODS: Mothers of 202 children aged 2-5 years were recruited in Taiwan. Maternal self-reported questionnaires on mobile device usage, shared reading, and child's emotional and behavioral development were collected. Multiple linear regression models were used for analyses. RESULTS: Mothers' higher usage time on mobile devices and an education level of college or less were significantly associated with the child's exceeding recommended use of mobile devices. Particularly among depressed mothers, preschoolers' exceeding recommended use of mobile devices was associated with more sleep (ß = 9.87, 95% confidence interval [CI] = 1.34, 18.40) and attention (ß = 7.20, 95% CI = 1.50, 12.91) problems, whereas shared reading was associated with less somatic complaints (ß = -16.19, 95% CI = -32.22, -0.15) and withdrawn (ß = -21.50, 95% CI = -40.52, -2.47), compared with their respective counterparts. CONCLUSION: Our study suggested the beneficial effects of shared reading. Moreover, we highlighted the adverse effects of preschoolers' exceeding recommended use of mobile device on sleep and attention problems, especially for children of mothers with depression.
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Comportamento Problema , Feminino , Humanos , Computadores de Mão , Depressão , Emoções , Mães/psicologia , Comportamento Problema/psicologia , Leitura , Pré-EscolarRESUMO
Recently, endometrial hyperplasia was identified as presenting a higher risk for progressing to endometrial carcinoma more readily than adenomyosis. The Lcn-2 gene encodes neutrophil gelatinase-associated lipocalin (NGAL), which promotes cell proliferation and serves as a cancer marker in some cancers. In our current study, we investigated the relationship between the expression of NGAL and that of pathogenic cytokines and cancer-related genes including cyclooxygenase-2 (COX-2), E-cadherin, ß-catenin, and vimentin in patients with endometrial disorders. NGAL expression was examined by Western blotting, immunohistochemistry, and reverse-transcription polymerase chain reaction (RT-PCR) in hyperplasia and adenomyosis biopsy samples. Immunohistochemistry demonstrated the occurrence of NGAL in glandular epithelial cells but not in the stromal cells of hyperplasia biopsy samples. NGAL protein and mRNA expression were significantly greater in endometrial hyperplasia than in endometrial adenomyosis. Although our data showed no difference in pathogenic cytokines between patients with endometrial hyperplasia and endometrial adenomyosis, we observed high expression levels of COX-2, ß-catenin, vimentin, and E-cadherin in patients with endometrial hyperplasia. NGAL mRNA expression correlated positively with COX-2 and E-cadherin mRNA expression (r = 0.41 and r = 0.57, respectively), but correlated negatively with vimentin and ß-catenin mRNA expression (r = -0.42 and r = -0.61, respectively). Our data suggest that NGAL is up-regulated in patients with endometrial hyperplasia to prevent the transition from hyperplasia to carcinoma.
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Proteínas de Fase Aguda/metabolismo , Biomarcadores Tumorais/metabolismo , Hiperplasia Endometrial/metabolismo , Endometriose/metabolismo , Lipocalinas/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Análise de Variância , Western Blotting , Caderinas/metabolismo , Ciclo-Oxigenase 2/metabolismo , Primers do DNA/genética , Células Epiteliais/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Lipocalina-2 , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Vimentina/metabolismo , beta Catenina/metabolismoRESUMO
OBJECTIVE: To evaluate the effects of an integrated childbirth education intervention on reducing childbirth fear, anxiety, and depression, and improving dispositional mindfulness. DESIGN: A two-arm parallel, single-blind randomised controlled trial. SETTING: A teaching hospital in Northern Taiwan. PARTICIPANTS: Pregnant women ≥ 20 years of age with a singleton pregnancy (12-24 weeks gestation) and their support partners were recruited. All women included in the study had a score of ≥ 7 points on a fear of childbirth visual analogue scale. INTERVENTIONS: The intervention group (n = 53) received an 8-week course in a childbirth education programme, which included (1) childbirth education using simulation-based learning that highlighted coping with labour pain and (2) instruction in mindfulness breathing, body scans, stretching, sitting meditation, and mindfulness walking. Support partners were invited to participate. The control group (n = 53) received the usual standard prenatal care. MEASUREMENTS: The primary outcome of fear of childbirth was assessed using the Wijma Delivery Expectancy/Experience Questionnaire. The secondary outcomes of anxiety, depression, and dispositional mindfulness were assessed with the Edinburgh Postpartum Depression Scale, State-Trait Anxiety Inventory Scale, and the Mindful Attention Awareness Scale, respectively. Repeated data were collected at baseline, 36 weeks gestation, and 1 week postpartum. FINDINGS: Ninety-one mothers completed the study, with a mean age of 33.9 years (SD = 4.4), and most were primipara (n = 83). The baseline measurements did not differ between the groups. Compared with the control group, there were significant differences in all measures from baseline for the intervention group: the scores were significantly lower for fear of childbirth (mean difference (MD) =-14.8 â¼ -23.7, p < .01), symptoms of anxiety (MD =-7.4 â¼ -6.4, p < .01), and depression (MD =-3.7 â¼ -3.5, p < .01); the levels of dispositional mindfulness were significantly higher (MD =4.9 â¼ 5.7, p < .01) at 36 weeks gestation, and 1 week postpartum. CONCLUSION AND IMPLICATIONS FOR PRACTICE: The 8-week integrated childbirth education intervention was effective in reducing the fear of childbirth in pregnant women. The mindfulness techniques were easily learnt and applied by the participants. Using these techniques during pregnancy and labour enhanced participants' mental health and coping. The integrated childbirth education which includes pregnant women and their support partners could be easily taught by midwives in other contexts.
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Atenção Plena , Educação Pré-Natal , Adulto , Ansiedade/psicologia , Ansiedade/terapia , Depressão/terapia , Medo/psicologia , Feminino , Humanos , Lactente , Atenção Plena/métodos , Parto/psicologia , Gravidez , Educação Pré-Natal/métodos , Método Simples-CegoRESUMO
BACKGROUND: Although maternal mental illnesses have been found to influence child health and development, little is known about the impact of maternal positive well-being on child health and development. Therefore, this longitudinal study investigated the effects of prenatal subjective well-being on birth outcomes and child development by considering the potential modifier effect of parity. METHODS: Pregnant women in early stages of pregnancy were recruited at five selected hospitals in Taipei, Taiwan, during their prenatal appointments since 2011. Self-reported evaluations were conducted at seven time points up to 2 years postpartum. Linear regression and generalized estimating equation models were used for examination. RESULTS: Higher prenatal eudaimonic well-being was associated with longer gestational length (adjusted beta [aß] = 0.36, 95% confidence interval [CI] = 0.03, 0.68) and higher birth weight (aß = 124.71, 95% CI = 35.75, 213.66). Higher positive and negative affect were associated with longer gestational length (aß = 0.38, 95% CI = 0.06, 0.70) and smaller birth weight (aß = -93.51, 95% CI = -178.35, -8.67), respectively. For child's outcomes, we found an association between higher prenatal eudaimonic well-being and decreased risks of suspected developmental delay, particularly for children of multiparous mothers (adjusted odds ratio = 0.18, 95% CI = 0.05, 0.70). Higher levels of prenatal depression and anxiety were significantly associated with increased risks of suspected developmental delay for children of primiparous mothers. CONCLUSIONS: Positive prenatal maternal mental health may benefit birth outcomes and child development, particularly for children of multiparous mothers. Interventions for improving prenatal mental health may be beneficial for child development.
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Mães , Período Pós-Parto , Criança , Gravidez , Humanos , Feminino , Estudos Longitudinais , Peso ao Nascer , Período Pós-Parto/psicologia , Desenvolvimento InfantilRESUMO
PURPOSE: To compare the risk of neurodevelopmental disorders in children conceived via intracytoplasmic sperm injection (ICSI) and those conceived naturally. MATERIALS AND METHODS: A population-based cohort study using data retrieved from the Taipei Medical University Research Database (TMURD) from January, 2004 to August, 2016. The data included maternal pregnancy history, perinatal history and developmental follow up of their babies up to 5 years of age. The study included 23885 children, of whom 23148 were naturally conceived and 737 were conceived via ICSI. Neurodevelopmental disorders defined by 21 ICD-9-CM codes. RESULTS: Of the 23885 children enrolled for analysis, 2778 children were included for further subgrouping analysis after propensity matching to reduce bias from maternal factors. The single-birth group included 1752 naturally conceived (NC) children and 438 ICSI children. The multiple-birth group included 294 NC and 294 ICSI children. The risk of neurodevelopmental disorders was not increased for ICSI children in both groups (single birth: adjusted hazard ratio aHR = 0.70, 95% CI = 0.39-1.27, p = 0.243; multiple-birth group aHR = 0.77, 95% CI = 0.43-1.35, p = 0.853). In the single-birth group, multivariate analyses showed that male sex (aHR = 1.81, 95% CI = 1.29-2.54, p < 0.001), and intensive care unit (ICU) admission (aHR = 3.10, 95% CI = 1.64-5.86, p < 0.001) were risk factors for neurodevelopmental disorders. In the multiple-birth group, multivariate analyses demonstrated that ICU admission (aHR = 3.58, 95% CI = 1.82-7.04, p < 0.001), was risk factor for neurodevelopmental disorders. CONCLUSION: Our study indicated that the use of ICSI does not associated with higher risk of neurodevelopmental disorders in the offspring. But male sex, and ICU admission do have increased risk of neurodevelopmental disorders. However, long term follow up of this cohort on health outcomes in adolescence and adulthood will strengthen the conclusions that ICSI is safe regarding offspring long term outcome.
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Injeções de Esperma Intracitoplásmicas , Adulto , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva , Masculino , Gravidez , Gravidez MúltiplaRESUMO
The mechanism on how extracellular matrix (ECM) cooperates with niche growth factors and oxygen tension to regulate the self-renewal of embryonic germline stem cells (GSCs) still remains unclear. Lacking of an appropriate in vitro cell model dramatically hinders the progress. Herein, using a serum-free culture system, we demonstrated that ECM laminin cooperated with hypoxia and insulin-like growth factor 1 receptor (IGF-1R) to additively maintain AP activity and Oct-4 expression of AP+GSCs. We found the laminin receptor CD49f expression in d2 testicular GSCs that were surrounded by laminin. Laminin and hypoxia significantly increased the GSC stemness-related genes, including Hif-2α, Oct-4, IGF-1R, and CD49f. Cotreatment of IGF-1 and laminin additively increased the expression of IGF-IR, CD49f, Hif-2α, and Oct-4. Conversely, silencing IGF-1R and/or CD49f decreased the expression of Hif-2α and Oct-4. The underlying mechanism involved CD49f/IGF1R-(PI3K/AKT)-Hif-2α signaling loop, which in turn maintains Oct-4 expression, symmetric self-renewal, and cell migration. These findings reveal the additive niche laminin/IGF-IR network during early GSC development.
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Successful fertilization is tightly regulated by capacitation and decapacitation processes. Without appropriate decapacitation regulation, sperm would undergo a spontaneous acrosome reaction which leads to loss of fertilization ability. Seminal plasma is known to negatively regulate sperm capacitation. However, the suppressive mechanisms still remain unclear. In this study, we demonstrate the decapacitation mechanism of mouse seminal vesicle autoantigen (SVA) might target membrane sphingomyelin (SPM) and regulate plasma membrane Ca(2+)-ATPase (PMCA) activity. The SVA was shown to suppress sperm capacitation induced by a broad panel of capacitation factors (bovine serum albumin (BSA), PAF, and cyclodextrin (CD)). Furthermore, SVA significantly decreased [Ca(2+)](i) and NaHCO(3)-induced [cAMP](i). Cyclic AMP agonists bypassed the SVA's suppressive ability. Importantly, the SVA may regulate PMCA activity which was evidenced by the fact that the SVA decreased the [Ca(2+)](i) and intracellular pH (pH(i)) of sperm; meanwhile, a PMCA inhibitor (carboxyeosin) could reverse SVA's suppression of [Ca(2+)](i). The potential target of the SVA on membrane SPM/lipid rafts was highlighted by the high binding affinity of SPM-SVA (with a K(d) of ~3 µM) which was close to the IC(50) of SVA's suppressive activity. Additionally, treatment of mink lung epithelial cells with the SVA enhanced plasminogen activator inhibitor (PAI)-1 expression stimulated by tumor growth factor (TGF)-ß and CD. These observations supported the membrane lipid-raft targeting of SVA. In summary, in this paper, we demonstrate that the decapacitation mechanism of the SVA might target membrane sphingolipid SPM and regulate PMCA activity to lower [Ca(2+)](i), thereby decreasing the [cAMP](i) level and preventing sperm pre-capacitation.
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Autoantígenos/fisiologia , Cálcio/metabolismo , ATPases Transportadoras de Cálcio da Membrana Plasmática/metabolismo , Proteínas Secretadas pela Vesícula Seminal/fisiologia , Capacitação Espermática , Animais , AMP Cíclico/metabolismo , Concentração de Íons de Hidrogênio , Microdomínios da Membrana , Camundongos , Esfingolipídeos/metabolismoRESUMO
BACKGROUND: Precise sperm-oocyte interaction is a critical event for successful fertilization. However, the identity of molecules involved in this process in humans remains largely unknown. This report describes the identification and characterization of a novel cell-surface protein and its potential role in human sperm-oocyte interaction. METHODS AND RESULTS: We previously identified an orphan guanylyl cyclase receptor (mouse GC-G) highly enriched in mouse testis and involved in sperm activation. By using a comparative genomic approach, we found the homologue gene in human (hGC-G) composed of 21 exons, spanning a minimum of 48 kb on chromosome 10q25. Real-time RT-PCR analysis revealed hGC-G mRNA selectively expressed in testis but with low or no expression in all other tissues examined. Compared with mGC-G, the hGC-G transcript contains three 1-bp deletions and two in-frame termination codons, which results in a short putative receptor-like polypeptide. Western blot analysis with an anti-hGC-G-specific antibody confirmed the protein expression of hGC-G in human sperm lysate. Flow cytometry and confocal immunofluorescence analysis demonstrated the localization of hGC-G protein on the acrosome cap and equatorial segment of mature human sperm. In addition, an integrin-binding Arg-Gly-Asp (RGD) motif was found in the extracellular domain of hGC-G. Pre-incubation of the hGC-G RGD peptide with zona pellucida-free oocytes greatly decreased the binding of human sperm to hamster oocytes, which suggests a role for hGC-G role in sperm-oocyte interaction. CONCLUSIONS: hGC-G is a novel surface protein on human sperm and potentially mediates sperm-oocyte interaction through its RGD-containing motif.
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Proteínas de Membrana/fisiologia , Receptores Acoplados a Guanilato Ciclase/fisiologia , Espermatozoides/metabolismo , Acrossomo/metabolismo , Reação Acrossômica , Motivos de Aminoácidos , Sítios de Ligação , Western Blotting , Mapeamento Cromossômico , Cromossomos Humanos Par 10 , Citometria de Fluxo , Imunofluorescência , Humanos , Masculino , Proteínas de Membrana/química , Proteínas de Membrana/genética , RNA Mensageiro/metabolismo , Receptores Acoplados a Guanilato Ciclase/química , Receptores Acoplados a Guanilato Ciclase/genética , Análise de Sequência de DNA , Capacitação Espermática , Interações Espermatozoide-Óvulo , Testículo/metabolismoRESUMO
INTRODUCTION: Although an array of maternal and child-centered risks have been researched, considerably less is known about the effects of paternal influences on child's birth outcomes and early development. This longitudinal study thus examined the effects of paternal influences (parental stress, partner support, childcare and nursing, and father-child interaction) from early pregnancy to 2 years postpartum on pregnancy outcomes and toddlerhood development, with a simultaneous consideration of maternal depression. METHODS: Pregnant women together with their partners were recruited from 2011 to 2016 at five selected hospitals in Taipei, Taiwan. In total, 440 families completed seven assessments from early pregnancy to 2 years postpartum. Self-reported data were analyzed using logistic regression and generalized estimating equation models. RESULTS: The increment in parental stress from early to late pregnancy was independently and significantly associated with higher risks of low birthweight (adjusted odds ratio [aOR] = 5.3, 95% confidence interval [CI] = 1.0-27.7). In the postpartum years, paternal poorer childcare and nursing (aOR = 1.7, 95% CI = 1.0-3.0) and father-child interaction (aOR = 1.8, 95% CI = 1.2-2.9) were significantly associated with increased risks of child's suspected developmental delay up to 2 years postpartum, particularly among children of nondepressed mothers' children. LIMITATIONS: Selecting both parents in metropolitan areas with higher socioeconomic status may compromise the generalizability of the study. CONCLUSIONS: We suggested the essential role of longitudinal paternal influences from early pregnancy on birth outcomes and child's development during infancy and toddlerhood. Maternal depression remains critical to concern.
Assuntos
Pai , Mães , Criança , Desenvolvimento Infantil , Feminino , Humanos , Estudos Longitudinais , Masculino , Período Pós-Parto , Gravidez , TaiwanRESUMO
BACKGROUND: Low self-efficacy affects new mothers' ability to sustain breastfeeding. Interventions that increase self-efficacy could improve sustained breastfeeding. OBJECTIVES: To develop an integrated breastfeeding education program based on self-efficacy theory, and evaluate the effect of the intervention on first-time mothers' breastfeeding self-efficacy and attitudes. DESIGN: A single-blind, randomised controlled trial. SETTING: A prenatal clinic of a teaching hospital. PARTICIPANTS: First-time mothers with a singleton pregnancy (12-32 weeks' gestation) and their support partners were selected by convenience sampling (N = 104) and allocated by block-randomization to an intervention or control group. METHODS: A 3-week breastfeeding intervention program was developed based on self-efficacy theory. The intervention group received the breastfeeding program; the control group received standard care. Data between groups were compared for scores on breastfeeding self-efficacy, infant feeding attitude, and breastfeeding practice, which were assessed using the Breastfeeding Self-Efficacy Scale-Short Form, the Iowa Infant Feeding Attitude Scale, and a structured questionnaire, respectively. Repeated data measurements were collected at baseline, 36-weeks' gestation, and postpartum at 1-week, and 1-, 3-, and 6-months. RESULTS: Ninety-three mothers completed the study. Data were compared for the self-efficacy intervention group (n = 50) with the control group (n = 43). Baseline measures did not differ between groups. The intervention group had significantly higher breastfeeding self-efficacy at 36 weeks' gestation (mean difference (MD): 7.3, p < .001), and postpartum at 1-week (p < .001), 1-month (p < .001) and 3-months (p < .01) with MD: 6.7, 7.9, and 8.1, respectively; differences in scores from baseline were also significantly greater from 36 weeks' gestation to 3-months (MD from 9.1~9.9, p < .001) and 6-months postpartum (MD: 7.0, p < .05). Infant feeding attitude scores significantly improved from 36 weeks' gestation to 6-months postpartum for the intervention group (MD from 3.5~7.4, p < .05). Rates for exclusive and predominant breastfeeding postpartum were significantly higher for the intervention group vs control (p < .02) at 1-week (98% vs. 86%), 1-month (100% vs. 90.7%), and 3-months (94% vs. 76.7%). Odds ratio (OR) postpartum for exclusive and predominant breastfeeding was greater for the intervention group at 3-months (OR = 4.7, 95% Confidence interval (CI), 1.2 -18.6; p = .05) and for exclusive breastfeeding at 6-months (OR: 2.82, 95% CI 1.0-8.1; p = .05). CONCLUSIONS: The breastfeeding education intervention improved breastfeeding self-efficacy, infant feeding attitudes, and exclusive breastfeeding rates. The breastfeeding education program could be effective for sustaining breastfeeding in new mothers. TRIAL REGISTRATION: Registered with www.clinicaltrials.gov (NCT03807726).
Assuntos
Aleitamento Materno , Autoeficácia , Feminino , Humanos , Lactente , Mães , Período Pós-Parto , Gravidez , Método Simples-CegoRESUMO
OBJECTIVE: To determine the association between type of previous delivery (vaginal compared with cesarean) on the success of medical abortion with mifepristone-misoprostol in early pregnancy. METHODS: The records of 879 women with intrauterine pregnancies at or before 56 days of gestation who underwent medical abortions were reviewed. Medical treatment consisted of 600 mg mifepristone orally followed 48 hours later with oral misoprostol. An ultrasound examination was performed 14-21 days after treatment, and a successful medical abortion was defined as an empty uterus without surgical intervention. Univariable and multivariable logistic regressions were used to determine risk factors for failure of medical abortion. RESULTS: A total of 797 (90.7%) women had successful medical abortions; 82 (9.3%) had failed medical abortions. Multivariable logistic regression indicated that women with gestational ages greater than 42 days (odds ratio [OR] 2.53, 95% confidence interval [CI] 1.55-4.05) had higher odds of failed abortion compared with a gestational age less than 43 days. Parous women (OR> or =3.94, 95% CI 1.83-8.53) and those with prior cesarean delivery (OR 9.59, 95% CI 4.30-21.39) were more likely to have failed abortions compared with nulliparous women. Among 523 parous women (68 had failed abortion), those with gestational ages greater than 42 days (OR 2.07, 95% CI 1.22-3.50) and prior cesarean delivery (OR 3.33, 95% CI 1.95-5.69) were more likely to have failed abortions compared with those with gestational ages less than 43 days or with prior vaginal delivery. CONCLUSION: Parous women are at increased risk for failed medical abortion in comparison with nulliparous women. Prior cesarean delivery is significantly associated with failed medical abortion.