RESUMO
Pregnancy represents a stage during which maternal physiology and homeostatic regulation undergo dramatic change and adaptation. The fundamental purpose of these adaptations is to ensure the survival of her offspring through adequate nutrient provision and an environment that is tolerant to the semi-allogenic foetus. While poor maternal diet during pregnancy is associated with perturbed maternal adaptations during pregnancy, the influence of paternal diet on maternal well-being is less clearly defined. We fed C57BL/6 male mice either a control (CD), low protein diet (LPD), a high fat/sugar Western diet (WD) or the LPD or WD supplemented with methyl donors (MD-LPD and MD-WD, respectively) for a minimum of 8 weeks prior to mating with C57BL/6 females. Mated females were culled at day 17 of gestation for the analysis of maternal metabolic, gut, cardiac and bone health. Paternal diet had minimal influences on maternal serum and hepatic metabolite levels or gut microbiota diversity. However, analysis of the maternal hepatic transcriptome revealed distinct profiles of differential gene expression in response to the diet of the father. Paternal LPD and MD-LPD resulted in differential expression of genes associated with lipid metabolism, transcription, ubiquitin conjugation and immunity in dams, while paternal WD and MD-WD modified the expression of genes associated with ubiquitin conjugation and cardiac morphology. Finally, we observed changes in maternal femur length, volume of trabecular bone, trabecular connectivity, volume of the cortical medullar cavity and thickness of the cortical bone in response to the father's diets. Our current study demonstrates that poor paternal diet at the time of mating can influence the patterns of maternal metabolism and gestation-associated adaptations to her physiology.
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Adaptação Fisiológica , Camundongos Endogâmicos C57BL , Animais , Feminino , Gravidez , Masculino , Camundongos , Fenômenos Fisiológicos da Nutrição Materna , Dieta Ocidental , Fígado/metabolismo , Dieta com Restrição de Proteínas , Microbioma Gastrointestinal , Dieta , Dieta Hiperlipídica/efeitos adversos , Fenômenos Fisiológicos da Nutrição AnimalAssuntos
Dieta , Exercício Físico , Receptor do Peptídeo Semelhante ao Glucagon 1 , Obesidade , Saúde Reprodutiva , Humanos , Masculino , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Obesidade/complicações , Análise do Sêmen , Contagem de Espermatozoides , Motilidade dos Espermatozoides , EspermatozoidesRESUMO
BACKGROUND: There remains inconsistent data about the association of surgical approach and periprosthetic joint infection (PJI). We sought to evaluate the risk of reoperation for superficial infection and PJI after primary total hip arthroplasty (THA) in a multivariate model. METHODS: We reviewed 16,500 primary THAs, collecting data on surgical approach and all reoperations within 1 year for superficial infection (n = 36) or PJI (n = 70). Considering superficial infection and PJI separately, we used Kaplan-Meier survivorship to assess survival free from reoperation and a Cox Proportional Hazards multivariate models to assess risk factors for reoperation. RESULTS: Between direct anterior approach (DAA) (N = 3,351) and PLA (N = 13,149) cohorts, rates of superficial infection (0.4 versus 0.2%) and PJI (0.3 versus 0.5%) were low and survivorship free from reoperation for superficial infection (99.6 versus 99.8%) and PJI (99.4 versus 99.7%) were excellent at both 1 and 2 years. The risk of developing superficial infection increased with high body mass index (BMI) (hazard ratio [HR] = 1.1 per unit increase, P = .003), DAA (HR = 2.7, P = .01), and smoking status (HR = 2.9, P = .03). The risk of developing PJI increased with the high BMI (HR = 1.04, P = .03), but not surgical approach (HR = 0.68, P = .3). CONCLUSION: In this study of 16,500 primary THAs, DAA was independently associated with an elevated risk of superficial infection reoperation compared to the PLA, but there was no association between surgical approach and PJI. An elevated patient BMI was the strongest risk factor for superficial infection and PJI in our cohort. LEVEL OF EVIDENCE: III, retrospective cohort study.
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Artrite Infecciosa , Artroplastia de Quadril , Infecções Relacionadas à Prótese , Humanos , Estudos Retrospectivos , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/cirurgia , Artroplastia de Quadril/efeitos adversos , Artrite Infecciosa/etiologia , Fatores de Risco , Reoperação/efeitos adversos , PoliésteresRESUMO
There is growing evidence that poor paternal diet at the time of conception increase the risk of offspring developing a range of non-communicable metabolic diseases, such as obesity, diabetes and cardiovascular disease, in adulthood. We hypothesise that a paternal low protein-high carbohydrate diet perturbs offspring tissue lipid abundance through both sperm and seminal plasma-mediated mechanisms. To test our hypothesis, we fed male C57BL/6 mice either a control normal protein diet (NPD; 18% protein) or an isocaloric low protein diet (LPD; 9% protein) for a minimum of 8 weeks. We generated offspring through artificial insemination, in combination with vasectomised male mating. Using this approach, we derived offspring from either NPD or LPD sperm but in the presence of NPD or LPD seminal plasma. Using high resolution mass-spectrometry, we found that offspring derived from either LPD sperm or seminal fluid displayed perturbed cardiac and brain lipid abundance from just three weeks of age, typically associated with the altered abundance of tissue triglycerides. We also observed the differential sex-specific patterns of lipids between the control and experimental offspring's hearts and brains. These observations indicate that poor paternal diet at the time of conception affects offspring cardiac and brain lipid profiles in an age-, sex- and generation-specific manner.
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Encéfalo , Sêmen , Feminino , Camundongos , Masculino , Animais , Camundongos Endogâmicos C57BL , Homeostase , LipídeosRESUMO
BACKGROUND: Perioperative intra-articular joint injection is a known risk factor for developing prosthetic joint infection (PJI) in the immediate preoperative and postoperative periods for total knee arthroplasty, but is less defined in unicompartmental knee arthroplasty (UKA). The goal of this study was to elucidate the risk of developing PJI after intra-articular corticosteroid injection (IACI) into a post UKA knee. METHODS: A retrospective review of a nationwide administrative claims database was performed from January 2015 to October 2020. Patients who underwent UKA and had an ipsilateral IACI were identified and matched 2:1 to a control group of primary UKA patients who did not receive IACI. Multivariate logistic analyses were conducted to assess differences in PJI rates at 6 months, 1 year, and 2 years. RESULTS: A total of 47,903 cases were identified, of which 2,656 (5.5%) cases received IACI. The mean time from UKA to IACI was 355 days. The incidence of PJI in the IACI group was 2.7%, compared to 1.3% in the control group. The rate of PJI after IACI was significantly higher than the rate in the control group at 6 months, 1 year, and 2 years (all P < .05). The majority of PJI occurred within the first 6 months following IACI (75%). CONCLUSION: In this study, IACI in a UKA doubled the risk of PJI compared to patients who did not receive an injection. Surgeons should be aware of this increased risk to aid in their decision-making about injecting into a UKA. LEVEL OF EVIDENCE: III, retrospective comparative study.
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Artroplastia do Joelho , Osteoartrite do Joelho , Infecções Relacionadas à Prótese , Humanos , Artroplastia do Joelho/efeitos adversos , Articulação do Joelho/cirurgia , Estudos Retrospectivos , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/induzido quimicamente , Corticosteroides/efeitos adversos , Osteoartrite do Joelho/complicaçõesRESUMO
As adults, our health can be influenced by a range of lifestyle and environmental factors, increasing the risk for developing a series of non-communicable diseases such as type 2 diabetes, heart disease and obesity. Over the past few decades, our understanding of how our adult health can be shaped by events occurring before birth has developed into a well-supported concept, the Developmental Origins of Health and Disease (DOHaD). Supported by epidemiological data and experimental studies, specific mechanisms have been defined linking environmental perturbations, disrupted fetal and neonatal development and adult ill-health. Originally, such studies focused on the significance of poor maternal health during pregnancy. However, the role of the father in directing the development and well-being of his offspring has come into recent focus. Whereas these studies identify the individual role of each parent in shaping the long-term health of their offspring, few studies have explored the combined influences of both parents on offspring well-being. Such understanding is necessary as parental influences on offspring development extend beyond the direct genetic contributions from the sperm and oocyte. This article reviews our current understanding of the parental contribution to offspring health, exploring some of the mechanisms linking parental well-being with gamete quality, embryo development and offspring health.
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Diabetes Mellitus Tipo 2 , Dieta , Desenvolvimento Embrionário/genética , Feminino , Humanos , Masculino , Obesidade , Gravidez , SêmenRESUMO
The underlying mechanisms driving paternally-programmed metabolic disease in offspring remain poorly defined. We fed male C57BL/6 mice either a control normal protein diet (NPD; 18% protein) or an isocaloric low protein diet (LPD; 9% protein) for a minimum of 8 weeks. Using artificial insemination, in combination with vasectomised male mating, we generated offspring using either NPD or LPD sperm but in the presence of NPD or LPD seminal plasma. Offspring from either LPD sperm or seminal fluid display elevated body weight and tissue dyslipidaemia from just 3 weeks of age. These changes become more pronounced in adulthood, occurring in conjunction with altered hepatic metabolic and inflammatory pathway gene expression. Second generation offspring also display differential tissue lipid abundance, with profiles similar to those of first generation adults. These findings demonstrate that offspring metabolic homeostasis is perturbed in response to a suboptimal paternal diet with the effects still evident within a second generation.
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Dieta com Restrição de Proteínas , Sêmen , Animais , Pai , Homeostase , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
The association between maternal metabolic status at the time of conception and subsequent embryogenesis and offspring development has been studied in detail. However, less attention has been given to the significance of paternal nutrition and metabolism in directing offspring health. Despite this disparity, emerging evidence has begun to highlight an important connection between paternal metabolic well-being, semen quality, embryonic development and ultimately adult offspring health. This has established a new component within the Developmental Origins of Health and Disease hypothesis. Building on the decades of understanding and insight derived from the numerous models of maternal programming, attention is now becoming focused on defining the mechanisms underlying the links between paternal well-being, post-fertilisation development and offspring health. Understanding how the health and fitness of the father impact on semen quality is of fundamental importance for providing better information to intending fathers. Furthermore, assisted reproductive practices such as in vitro fertilisation rely on our ability to select the best quality sperm from a diverse and heterogeneous population. With considerable advances in sequencing capabilities, our understanding of the molecular and epigenetic composition of the sperm and seminal plasma, and their association with male metabolic health, has developed dramatically over recent years. This review will summarise our current understanding of how a father's metabolic status at the time of conception can affect sperm quality, post-fertilisation embryonic and fetal development and offspring health.
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Análise do Sêmen , Sêmen , Adulto , Pai , Feminino , Humanos , Masculino , Gravidez , Reprodução , Espermatozoides/metabolismoRESUMO
INTRODUCTION: Lesser tuberosity osteotomy (LTO) and subscapularis peel (Peel) are 2 common techniques used to mobilize the subscapularis tendon during anatomic total shoulder arthroplasty (TSA). The literature is inconclusive over which technique is optimal; thus, controversy exists over which technique should be performed. The purpose of this study was to compare specific functional internal rotation tasks and general outcome scores in TSA patients who received either an LTO or Peel. METHODS: A retrospective review of 563 patients treated with primary TSA using either an LTO (n = 358) or Peel (n = 205) with a minimum 2-year follow-up was performed. Subjective internal rotation, active internal rotation, and specific questions related to functional internal rotation isolated from the Simple Shoulder Test (SST) and American Shoulder and Elbow Surgeons functional questionnaires were reviewed. Other outcome scores including visual analog scale pain and function, Single Assessment Numerical Evaluation, SST, American Shoulder and Elbow Surgeons, and revision rates were compared between the 2 groups. RESULTS: The study found no difference in postoperative functional internal rotation and range of motion between LTO and Peel. Patients who received a Peel were shown to have a slightly greater improvement in the ability to perform toileting and a higher average change in SST score that did not reach clinical significance. There was no difference in the percentage of maximal improvement, revision rate, or need for revision between the 2 groups. CONCLUSION: No difference was found between the LTO and Peel techniques in regard to functional tasks of internal rotation at short-term follow-up.
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Artroplastia do Ombro , Articulação do Ombro , Humanos , Artroplastia do Ombro/efeitos adversos , Seguimentos , Osteotomia/métodos , Amplitude de Movimento Articular , Estudos Retrospectivos , Manguito Rotador/cirurgia , Articulação do Ombro/cirurgia , Resultado do TratamentoRESUMO
Background: Early discharge has been a target of cost control efforts, given the growing demand for joint replacement surgery. Select patients are given the choice for same-day discharge (SDD) or overnight stay after shoulder arthroplasty. The COVID-19 pandemic changed patient perspectives regarding hospital visitation and admission. The purpose of this study was to determine if the COVID-19 pandemic impacted the utilization of SDD after shoulder arthroplasty. We hypothesize that patients undergoing shoulder arthroplasty after the start of the COVID-19 pandemic will have higher rates of SDD. Methods: A retrospective continuous review was performed on 370 patients who underwent a primary anatomic (total shoulder arthroplasty) or reverse shoulder arthroplasty between August 2019 and December 2020 by a single surgeon. This group of patients represent the 185 arthroplasty cases completed before the COVID-19 pandemic and the first 185 patients after the start of the pandemic. April 1, 2020, was chosen as the cutoff for pre-COVID patients, as this represents the date a statewide ban on elective surgery was declared. All patients were counseled preoperatively regarding SDD and given the choice to stay overnight, unless medically contraindicated. Demographics, medical history, length of stay, 30- and 90-day readmissions, and 90-day emergency room (ER) and urgent care visits were obtained from medical records and compared. Two-tailed student t-tests, chi-square tests, and Fischer's exact were performed where appropriate. Results: The 2 groups were similar in age, body mass index, gender distribution, and Outpatient Arthroplasty Risk Assessment score. During the collection period, there were more anatomic shoulder arthroplasties performed after (54%) than before (44%) the COVID-19 pandemic (P = .029). Patients treated after the start of the COVID-19 pandemic were almost 3 times more likely to have an SDD (P < .001), with 85.4% (158/185) of patients being discharged the same day after COVID-19, compared with 34.6% (64/185) before COVID-19. Discharge disposition (location of discharge) was significantly different, as 99% (183/185) of patients undergoing surgery after the start of the COVID-19 pandemic were discharged home, compared with 94% (174/185) of patients before COVID-19. There was no difference in 30-day readmissions, 90-day readmissions, and 90-day (ER) and urgent care visits between the 2 groups. Conclusion: Our study suggests that the COVID-19 pandemic has dramatically impacted patient choices for SDD within a single surgeon's practice, with nearly 3 times as many patients electing for SDD. Readmissions and ER visits were similar, indicating that SDD remains a safe alternative for patients after total shoulder arthroplasty and reverse shoulder arthroplasty. Level of evidence: Level III; Retrospective Comparative Study.
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BACKGROUND: The paternal diet affects lipid metabolism in offspring for at least two generations through nutritional programming. However, we do not know how this is propagated to the offspring. OBJECTIVES: We tested the hypothesis that the changes in lipid metabolism that are driven by paternal diet are propagated through spermatozoa and not seminal plasma. METHODS: We applied an updated, purpose-built computational network analysis tool to characterise control of lipid metabolism systemically (Lipid Traffic Analysis v2.3) on a known mouse model of paternal nutritional programming. RESULTS: The analysis showed that the two possible routes for programming effects, the sperm (genes) and seminal plasma (influence on the uterine environment), both have a distinct effect on the offspring's lipid metabolism. Further, the programming effects in offspring suggest that changes in lipid distribution are more important than alterations in lipid biosynthesis. CONCLUSIONS: These results show how the uterine environment and genes both affect lipid metabolism in offspring, enhancing our understanding of the link between parental diet and metabolism in offspring.
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Metabolismo dos Lipídeos , Sêmen , Animais , Pai , Humanos , Masculino , Metabolômica , Camundongos , Espermatozoides/metabolismoRESUMO
ABSTRACT: Orthopaedic surgery research increasingly utilizes statistical models to adjust for confounding, provide additional precision, and describe complex relationships. Traditionally, a statistical model is termed "multivariable" if it examines the relationship between multiple independent variables (e.g., covariables). The term "multivariate" is used to describe statistical models with multiple dependent variables (e.g., outcomes). The precise use of statistical terminology is important for study appraisal and reproducibility. The term "multivariate" is frequently used incorrectly in the orthopaedic literature to describe statistical models with a single dependent variable. In our analysis, we found that the term "multivariate" was used frequently, and in >90% of cases, the term was used to describe models that contain only a single dependent variable. Consistent with our perception, the terms "multivariable" and "multivariate" are not used with optimal precision. Below, we discuss the impact of the misuse of statistical terminology and present suggestions for improving statistical reporting.
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Prior research consistently finds that gang youth, compared to nongang youth, are more involved in risky behaviors such as violence and drug sales. Less attention has been given to comparisons in sexual behavior. While research demonstrates that gang membership is associated with risky sex and many gang members indicate that sex is a motivation for joining a gang, prior research is limited in its ability to account for self-selection into a gang, variations in involvement across gender, and different forms of sexual activity. This research addresses these limitations by using Add Health data and propensity score matching to examine the relationship between gang membership and sexual behavior inside and out of a romantic relationship as well as how this relationship differs by gender. While findings indicate that gang membership increases the likelihood of sexual intercourse, nonromantic sex, and the number of nonromantic sex partners, no unique gender differences were identified.
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Detailed molecular analysis is of increasing importance in research into the regulation of biochemical pathways, organismal growth and disease. Lipidomics in particular is increasingly sought after as it provides insight into molecular species involved in energy storage, signalling and fundamental cellular structures. This has led to the use of a range of tools and techniques to acquire lipidomics data. 31P NMR for lipidomics offers well-resolved head group/lipid class analysis, structural data that can be used to inform and strengthen interpretation of mass spectrometry data and part of a priori structural determination. In the present study, we codify the use of 31P NMR for lipidomics studies to make the technique more accessible to new users and more useful for a wider range of questions. The technique can be used in isolation (phospholipidomics) or as a part of determining lipid composition (lipidomics). We describe the process from sample extraction to data processing and analysis. This pipeline is important because it allows greater thoroughness in lipidomics studies and increases scope for answering scientific questions about lipid-containing systems.
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Lipidômica/métodos , Lipídeos/química , Espectroscopia de Ressonância Magnética/métodos , Isótopos de Fósforo/química , Animais , CamundongosAssuntos
Dieta Hiperlipídica , Pai , Dieta Hiperlipídica/efeitos adversos , Feminino , Humanos , Masculino , Gravidez , SêmenRESUMO
BACKGROUND: Postpartum haemorrhage (PPH) is a major cause of maternal morbidity and mortality and its incidence is increasing in many countries despite management guidelines. A national quality improvement programme called the Obstetric Bleeding Strategy for Wales (OBS Cymru) was introduced in all obstetric units in Wales. The aim was to reduce moderate PPH (1000 mL) progressing to massive PPH (> 2500 mL) and the need for red cell transfusion. METHODS: A PPH care bundle was introduced into all 12 obstetric units in Wales included all women giving birth in 2017 and 2018 (n = 61,094). The care bundle prompted: universal risk assessment, quantitative measurement of blood loss after all deliveries (as opposed to visual estimation), structured escalation to senior clinicians and point-of-care viscoelastometric-guided early fibrinogen replacement. Data were submitted by each obstetric unit to a national database. Outcome measures were incidence of massive PPH (> 2500 mL) and red cell transfusion. Analysis was performed using linear regression of the all Wales monthly data. RESULTS: Uptake of the intervention was good: quantitative blood loss measurement and risk assessment increased to 98.1 and 64.5% of all PPH > 1000 mL, whilst ROTEM use for PPH > 1500 mL increased to 68.2%. Massive PPH decreased by 1.10 (95% CI 0.28 to 1.92) per 1000 maternities per year (P = 0.011). Fewer women progressed from moderate to massive PPH in the last 6 months, 74/1490 (5.0%), than in the first 6 months, 97/1386 (7.0%), (P = 0.021). Units of red cells transfused decreased by 7.4 (95% CI 1.6 to 13.2) per 1000 maternities per year (P = 0.015). Red cells were transfused to 350/15204 (2.3%) and 268/15150 (1.8%) (P = 0.001) in the first and last 6 months, respectively. There was no increase in the number of women with lowest haemoglobin below 80 g/L during this time period. Infusions of fresh frozen plasma fell and there was no increase in the number of women with haemostatic impairment. CONCLUSIONS: The OBS Cymru care bundle was feasible to implement and associated with progressive, clinically significant improvements in outcomes for PPH across Wales. It is applicable across obstetric units of widely varying size, complexity and staff mixes.
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Transfusão de Eritrócitos/estatística & dados numéricos , Hemorragia Pós-Parto , Feminino , Humanos , Hemorragia Pós-Parto/epidemiologia , Hemorragia Pós-Parto/prevenção & controle , Hemorragia Pós-Parto/terapia , Período Pós-Parto , Gravidez , Melhoria de Qualidade , Medição de Risco , País de Gales/epidemiologiaRESUMO
In this paper we present an investigation of parental-diet-driven metabolic programming in offspring using a novel computational network analysis tool. The impact of high paternal carbohydrate intake on offsprings' phospholipid and triglyceride metabolism in F1 and F2 generations is described. Detailed lipid profiles were acquired from F1 neonate (3 weeks), F1 adult (16 weeks) and F2 neonate offspring in serum, liver, brain, heart and abdominal adipose tissues by MS and NMR. Using a purpose-built computational tool for analysing both phospholipid and fat metabolism as a network, we characterised the number, type and abundance of lipid variables in and between tissues (Lipid Traffic Analysis), finding a variety of reprogrammings associated with paternal diet. These results are important because they describe the long-term metabolic result of dietary intake by fathers. This analytical approach is important because it offers unparalleled insight into possible mechanisms for alterations in lipid metabolism throughout organisms.
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Carboidratos da Dieta/efeitos adversos , Metabolismo dos Lipídeos , Exposição Paterna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Animais , Animais Recém-Nascidos , Dieta/efeitos adversos , Feminino , Lipídeos/análise , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Distribuição TecidualRESUMO
Pregnancy represents a time of dramatic physiological adaptation by the mother in which dramatic changes in maternal cardiovascular, metabolic and immune systems occur. These adaptations, initiated from the earliest stages of gestation, are crucial for the implantation and continued development of the embryo, the establishment of the placenta and the growth of the fetus. Impairments in the normal adaptation of the maternal cardiovascular, metabolic and immune systems underlie the aetiology of gestational disorders such as preeclampsia and gestational diabetes. Studies have shown that the development of such gestational complications not only affects the well-being of the mother but also the short- and long-term health of her offspring. While the connection between maternal lifestyle factors and the development of gestational disorders such as preeclampsia and gestational diabetes has been studied in detail, the link between a father's lifestyle and the well-being of the mother during pregnancy has received less attention. In this review, we will explore the evidence that a range of paternal factors, such as age and diet, at the time of conception can not only affect the development of his offspring, but also the well-being of the mother during pregnancy. In addition, we will examine the sperm- and seminal plasma-specific mechanisms that connect the health of the father with that of the mother and his offspring.
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Saúde Materna , Complicações na Gravidez , Dieta , Pai , Feminino , Humanos , Masculino , Gravidez , SêmenRESUMO
Adverse programming of adult non-communicable disease can be induced by poor maternal nutrition during pregnancy and the periconception period has been identified as a vulnerable period. In the current study, we used a mouse maternal low-protein diet fed either for the duration of pregnancy (LPD) or exclusively during the preimplantation period (Emb-LPD) with control nutrition provided thereafter and postnatally to investigate effects on fetal bone development and quality. This model has been shown previously to induce cardiometabolic and neurological disease phenotypes in offspring. Micro 3D computed tomography examination at fetal stages Embryonic day E14.5 and E17.4, reflecting early and late stages of bone formation, demonstrated LPD treatment caused increased bone formation of relative high mineral density quality in males, but not females, at E14.5, disproportionate to fetal growth, with bone quality maintained at E17.5. In contrast, Emb-LPD caused a late increase in male fetal bone growth, proportionate to fetal growth, at E17.5, affecting central and peripheral skeleton and of reduced mineral density quality relative to controls. These altered dynamics in bone growth coincide with increased placental efficiency indicating compensatory responses to dietary treatments. Overall, our data show fetal bone formation and mineral quality is dependent upon maternal nutritional protein content and is sex-specific. In particular, we find the duration and timing of poor maternal diet to be critical in the outcomes with periconceptional protein restriction leading to male offspring with increased bone growth but of poor mineral density, thereby susceptible to later disease risk.