Future Health Of Offspring Research Articles

Sperm epigenetics landscape: correlation with embryo quality, reproductive outcomes and offspring's health.

Epigenetics refers to how gene expression and function are modulated without modifying the DNA sequence but through subtle molecular changes or interactions with it. As spermatogenesis progresses, male germ cells suffer plenty of epigenetic modifications, resulting in the definitive epigenome of spermatozoa conditioning its functionality, and this process can be altered by several internal and external factors. The paternal epigenome is crucial for sperm function, fertilization, embryo development, and offspring's health, and altered epigenetic states are associated with male infertility with or without altered semen parameters, embryo quality impairment, and worse ART outcomes together with the future offspring's health risks mainly through intergenerational transmission of epigenetic marks. Identifying epigenetic biomarkers may improve male factor diagnosis and the development of targeted therapies, not only to improve fertility but also to allow an early detection of risk and disease prevention in the progeny. While still there is much research to be done, hopefully in the near future, improvements in high-throughput technologies applied to epigenomes will permit our understanding of the underlying epigenetic mechanisms and the development of diagnostics and therapies leading to improved reproductive outcomes. In this review, we discuss the mechanisms of epigenetics in sperm and how epigenetics behave during spermatogenesis. Additionally, we elaborate on the relationship of sperm epigenetics with sperm parameters and male infertility, and highlight the impact of sperm epigenetic alterations on sperm parameters, embryo quality, ART outcomes, miscarriage rates and offspring's health. Furthermore, we provide insights into the future research of epigenetic alterations in male infertility.

Future Offspring Costs in Economic Evaluation.

Economic evaluation guidelines increasingly prescribe inclusion of all future costs. We point at an important dimension of future costs that is systematically neglected. Healthcare can affect future offspring, either through affecting the patient's fertility or through determining future offspring's health. As we show, the future costs associated with these changes can be substantial and will vary across interventions and demographic groups. However, systematic inclusion of these future offspring costs would raise many problems on its own. Based on the population ethics concept of necessitarianism, we suggest that only those future costs that spring from 'necessary' future lives should be included in future cost calculations, while all costs associated with 'potential' future lives can be ignored. This approach allows excluding most future offspring costs and avoids skewed cost-effectiveness outcomes of interventions with fertility effects, while taking into account the economic implications of preventing disease in future generations that will exist by necessity. Overall, future generations expose a substantial gap in today's Health Technology Assessment (HTA) methodology and further discussion of the issues they raise is needed.

Paternal low protein diet and the supplementation of methyl-donors impact fetal growth and placental development in mice

IntroductionPaternal low-protein diet can alter sperm methylation status, fetal growth and program offspring ill-health, however its impact on the placenta remains poorly defined. Here we examine the influence paternal low-protein diet has on fetal and placental development and the additional impact of supplementary methyl-donors on fetoplacental physiology. MethodsMale C57BL/6J mice were fed a control normal protein diet (NPD; 18% protein), a low-protein diet (LPD; 9% protein) or LPD with methyl-donor supplementation (MD-LPD; choline chloride, betaine, methionine, folic acid, vitamin B12) for a minimum of 8 weeks. Males were mated with 8–11 week old female C57BL/6J mice and fetal and placental tissue collected on embryonic day 17.5. ResultsPaternal LPD was associated with increased fetal weights compared to NPD and MD-LPD with 22% fetuses being above the 90th centile for fetal weight. However, LPD and MD-LPD placental weights were reduced when compared to NPD. Placentas from LPD fathers demonstrated a reduced junctional zone area and reduced free-fatty acid content. MD-LPD placentas did not mirror these finding, demonstrating an increased chorion area, a reduction in junctional-specific glycogen staining and reduced placental Dnmt3bexpression, none of which were apparent in either NPD or LPD placentas. DiscussionA sub-optimal paternal diet can influence fetal growth and placental development, and dietary methyl-donor supplementation alters placental morphology and gene expression differentially to that observed with LPD alone. Understanding how paternal diet and micro-nutrient supplementation influence placental development is crucial for determining connections between paternal well-being and future offspring health.

EFFECT OF MATERNAL HIGH-FAT DIET ON SERUM BRAIN-DERIVED NEUROTROPHIC FACTOR AND BEHAVIORAL REACTIONS IN MALE OFFSPRING OF WISTAR RATS

Maternal diet affects the development and health of future offspring. Recent studies indicate that excess fat in the female’s diet can influence the structure and function of the brain of her pups. An important role in the maturation of the central nervous system (CNS) and the maintenance of its functioning assigned to brain-derived neurotrophic factor (BDNF). Changes in BDNF concentration in the brain are associated with the occurrence of various neurobehavioral and mental disorders. In this work, we studied the behavioral reactions and the level of serum BDNF in male Wistar rats whose mothers before, during pregnancy and during lactation consumed food with excess fat (20 % of the total daily calorie content) and in the offspring of females who consumed standard diet of vivarium. As a result, an impairment of spatial learning and memory was revealed, as well as increased anxiety in the Morris Water Maze, Elevated plus Maze and Open Field in pups whose mothers were on a high-fat diet. These disorders were combined with a reduced level of BDNF in the peripheral blood. The data obtained indicate that high maternal fat consumption before pregnancy, during prenatal and early postnatal period, contributes to the formation of neurobehavioral disorders in offspring, which is probably associated with reduced BDNF levels in peripheral blood, and consequently in the brain. Характер питания матери оказывает влияние на развитие и состояние здоровья ее будущего потомства. Результаты недавних исследований указывают на то, что избыточное количество жиров в рационе самки способно оказывать воздействие на структуру и функционирование мозга ее детенышей. Важная роль в созревании центральной нервной системы и поддержании ее функционирования отводится мозговому нейротрофическому фактору ( BDNF ). Изменение его содержания в мозге связывают с возникновением различных нейроповеденческих нарушений и психических расстройств. В данной работе были исследованы особенности поведенческих реакций и содержание БДНФ в сыворотке крови самцов крыс линии Вистар, чьи матери до, во время беременности и в период лактации потребляли пищу с избыточным содержанием жира (20% от общей суточной калорийности) и у потомства самок, потреблявших стандартный рацион вивария. В результате было выявлено нарушение пространственного обучения и памяти, а также повышение уровня тревожности в тестах «Водный лабиринт Морриса», «Приподнятый крестообразный лабиринт» и «Открытое поле» у детенышей, чьи матери находились на высокожировой диете. Эти нарушения сочетались у них со сниженным уровнем БДНФ в периферической крови. Полученные данные указывают на то, что потребление самкой высокожировой диеты до беременности, в пренатальный и ранний постнатальный период способствует формированию у ее потомства нейроповеденческих нарушений, что вероятно связано со снижением БДНФ в периферической крови, а следовательно и уровня его экспрессии в головном мозге. 800x600 Normal 0 false false false RU X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:Обычная таблица; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:Times New Roman,serif;}

Induced DNA hypomethylation by Folic Acid Deprivation in Bovine Fibroblast Donor Cells Improves Reprogramming of Somatic Cell Nuclear Transfer Embryos

Aberrant patterns of DNA methylation are consistent events in SCNT derived embryos and mechanistically are believed to be related to abnormal development. While some epigenetic drugs have been used in attempts to improve SCNT efficiency but some concerns remained toward the safety of these drugs on the health of future offspring. Folate is an essential cofactor in one‐carbon cycle for conversion of homocysteine to methionine, thereby ensuring supply of SAM, the universal methyl donor for many biological methylation reactions including DNA methylation. Therefore, in vitro DNA hypo-methylation can be induced by folate deprivation and this study aims at deciphering the role of folic acid deprivation in culture medium of BFFs for 6 days on SCNT efficiency. Our data revealed that culture of fibroblast cells in folate− medium containing 0.5% FBS did not alter the cell cycle compared to other groups. Flowcytometric analysis revealed that DNA methylation (5-mC level) in folate deprived cells cultured in 0.5% serum was decreased compared to folate+ group. The result of bisulfite sequencing was in accordance with flowcytometric analysis, which indicated a decrease in DNA methylation of POU5F1 promoter. Gene expression analysis revealed an increase in expression of POU5F1 gene in folate− group. The nuclear area of the cells in folate− group was significantly larger than folate+ group. Induced DNA hypomethylation by folate deprivation in the folate− group significantly improved blastocyst rate compared to the folate+ group. DNA methylation level in POU5F1 promoter and ICR of H19 and IGF2 of SCNT derived embryos in the folate− group was similar to the IVF derived blastocysts. In conclusion, our results proposes a promising “non-chemical” instead of “chemical” approach using inhibitors of epigenetic modifier enzymes for improving mammalian SCNT efficiency for agricultural and biomedical purposes.

Psychological impediments to marriage - forensic and psychiatric opinions. Part I.

There are two types of proceedings before common courts for annulment of marriages during which expert psychiatrists are appointed. In the first type, the key task of the expert is to assess whether the presence of mental illness or mental retardation at the date of the marriage could possibly pose a threat to the marriage or health of future offspring. The expert performs a retrospective assessment not only of the course and severity of psychiatric disorders strictly distinguished by the legislator, but also their impact on the social functioning of a given person. In the second type of proceedings, marriage annulment is possible when the declaration of conclusion of a marriage was made by a prospective spouse who for whatever reason was in the state that excluded conscious expression of will. The task of the expert in this case is to assess the ability to perform a specific legal act. The aim of the analysis was to discuss problematic and unclear legal formulations concerning marriage annulment, which pose difficulties to psychiatrists and cause that sometimes opinions should only be prepared with a certain probability. Itis particularly troublesome to assess the impactof parent's mental dysfunctions on the health of future offspring. An additional element hindering the forensic and psychiatric evaluation is an analysis of the influence of the environment (including attitudes and behaviours of a healthy spouse) on the picture and the course of mental disorders of an ill or handicapped prospective spouse.

Sperm Epigenetics and Its Impact on Male Fertility, Pregnancy Loss, and Somatic Health of Future Offspring.

Sperm Epigenetics and Its Impact on Male Fertility, Pregnancy Loss, and Somatic Health of Future Offspring.

Biological features of placental programming

The placenta is a key organ in programming the fetus for later disease. This review outlines nine of many structural and physiological features of the placenta which are associated with adult onset chronic disease. 1) Placental efficiency relates the placental mass to the fetal mass. Ratios at the extremes are related to cardiovascular disease risk later in life. 2) Placental shape predicts a large number of disease outcomes in adults but the regulators of placental shape are not known. 3) Non-human primate studies suggest that at about mid-gestation, the placenta becomes less plastic and less able to compensate for pathological stresses. 4) Recent studies suggest that lipids have an important role in regulating placental metabolism and thus the future health of offspring. 5) Placental inflammation affects nutrient transport to the fetus and programs for later disease. 6) Placental insufficiency leads to inadequate fetal growth and elevated risks for later life disease. 7) Maternal height, fat and muscle mass are important in combination with placental size and shape in predicting adult disease. 8) The placenta makes a host of hormones that influence fetal growth and are related to offspring disease. Unfortunately, our knowledge of placental growth and function lags far behind that of other organs. An investment in understanding placental growth and function will yield enormous benefits to human health because it is a key player in the origins of the most expensive and deadly chronic diseases that humans face.

Young adult female cancer survivors' unmet information needs and reproductive concerns contribute to decisional conflict regarding posttreatment fertility preservation.

Many young adult female cancer survivors (YAFCS) are at risk of experiencing premature menopause. The current study characterized the posttreatment fertility information needs, reproductive concerns, and decisional conflict regarding future options for posttreatment fertility preservation (FP) among YAFCS. Participants completed a Web-based, anonymous survey between February and March 2015. The survey included investigator-designed questions of perceived information needs, the Reproductive Concerns After Cancer Scale, and the Decisional Conflict Scale. Analyses included Pearson correlation coefficients, independent-sample Student t tests, and multiple regression. There was a total of 346 participants with an average age of 29.9 years (SD = 4.1 years) who were 4.9 years from treatment (SD = 5.4 years [range, 0-27 years]). The main analyses focused on a subgroup of YAFCS with uncertain fertility status who had not previously undergone/attempted FP and either wanted future children or were unsure (179 women). Across fertility information topics, 43% to 62% of participants reported unmet information needs. The greatest reproductive concerns were related to fertility potential and the health of future offspring. The regression model controlled for a priori covariates including current age, age at treatment completion, income, relationship status, nulliparity, and prior fertility evaluation. Greater unmet information needs were found to be related to greater decisional conflict (β = .43; p<.001); greater reproductive concerns were associated at the trend level (β = .14, p = .08; F[8,118] = 6.42, p<.001). YAFCS with limited awareness or knowledge of their risk of experiencing premature menopause and FP options reported higher levels of decisional conflict regarding future FP. Posttreatment survivorship care should include comprehensive reproductive health counseling, including posttreatment FP options and family-building alternatives. Cancer 2016;122:2101-9. © 2016 American Cancer Society.

Transition and transfer of adolescents and young adults with pediatric onset chronic disease: the patient and parent perspective.

To determine patients' and parents' perceptions regarding the delivery of transition education and perceived barriers to transfer to adult oriented care. A self-report survey was administered to a convenience sample of patients (16-25 years old) with various childhood onset chronic diseases. A similar survey was administered to their parents/guardians. A total of 155 patients and 104 parents participated in the study. The mean age of patients was 18.8 ± 2.3 years; 57% were female. Although most patients and parents reported receiving information and training about their medical condition, significant gaps in other aspects of transition education were identified. These included stated deficiencies in education regarding unprotected intercourse, health of future offspring, birth control, pregnancy, illicit drug use, and future career or vocation counseling. Commonly cited barriers to transfer were emotional attachments and lack of adult medicine specialty providers; however, the majority anticipated being ready to transfer to adult oriented care by age 25 years. There are significant gaps in the delivery of transition education as perceived by patients and their parents. Standardization of transition education may help ensure that patients acquire the knowledge and skills for health care self-management in adulthood and successful transfer to adult oriented care.

Egg freezing for age-related fertility decline: preventive medicine or a further medicalization of reproduction? Analyzing the new Israeli policy

In December 2009, the Israel National Bioethics Council (INBC) issued recommendations permitting egg freezing to prevent both disease- and age-related fertility decline. The INBC report forms the basis of Israel's new policy regarding egg freezing. This article analyzes the medical section of the INBC's recommendations, comparing it with guidelines formulated by medical regulatory bodies in Europe and the United States. Our findings suggest that the INBC's recommendations consider age-related fertility decline to be a medical problem, and hence treat the new technology favorably, as preventive medicine, which we perceive as another instance of medicalization. The technology's risks are downplayed by the INBC, unlike the positions of medical organizations in both Europe and the United States, which consider the new technology experimental. This may culminate in raising false hopes about women's possible late genetic motherhood leading to involuntary future childlessness.

Impact of Caesarean section on the future health of offspring

Impact of Caesarean section on the future health of offspring