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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

There is now a significant body of human and animal model data which identify common associations between perturbed development during gestation, disproportionate fetal growth and poor adult cardiovascular and metabolic health. Typically, these studies focus on the impact of poor maternal health on offspring development and well-being. However, a growing evidence base now indicates that sub-optimal paternal factors (such as diet) can also program adult offspring ill-health. While the link between paternal health and offspring well-being is becoming established, attention is being focused on defining the underlying mechanism(s). Here, the father may influence post-fertilization development through two main pathways, the integrity and status of the sperm genome (including epigenome) and through components of the seminal plasma. We have used mouse models of poorquality diet to study the impact sub-optimal paternal nutrition has on the quality and epigenetic status of the sperm, embryonic development and fetal growth. We have also used our models to study the relative seminal plasma and sperm contributions to adult offspring cardiovascular and metabolic health. Our studies identify a continuum of changes ranging from testicular morphology, sperm epigenetic status, preimplantation embryo development, fetal growth and adult offspring cardio-metabolic ill-health in response to either over or undernutrition. Interestingly, we also observed that these long-term offspring effects appear mediated through specific sperm and seminal plasma specific mechanisms. Our data highlight the significance of a father's diet at the time of conception for the development and well-being of his offspring. [ABSTRACT FROM AUTHOR]

Introduction: Paternal 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., Methods: Male 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., Results: Paternal 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., Discussion: A 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Key Points: A low protein diet had minimal effects on paternal cardiovascular function or renin-angiotensin system activity. Paternal low protein diet modified F1 neonatal and adult offspring renin-angiotensin system activity and cardiovascular function in a sperm and/or seminal plasma specific manner. Paternal low protein diet modified F1 male offspring testicular expression of central epigenetic regulators. Significant changes in F2 neonatal offspring growth and tissue angiotensin-converting enzyme activity were programmed by paternal low protein diet in a sperm and/or seminal plasma specific manner., Abstract: Although the impact of maternal diet on adult offspring health is well characterized, the role that a father's diet has on his offspring's health remains poorly defined. We establish the significance of a sup-optimal paternal low protein diet for offspring vascular homeostasis and define the sperm and seminal plasma specific programming effects on cardiovascular health. Male C57BL6 mice were fed either a control normal protein diet (NPD; 18% protein) or an isocaloric low protein diet (LPD; 9% protein) for a minimum of 7 weeks. Using artificial insemination, in combination with vasectomized male mating, we generated offspring derived from either NPD or LPD sperm (devoid of seminal plasma) but in the presence of NPD or LPD seminal plasma (devoid of sperm). We observed that either LPD sperm or seminal fluid at conception impaired adult offspring vascular function in response to both vasoconstrictors and dilators. Underlying these changes in vascular function were significant changes in serum, lung and kidney angiotensin-converting enzyme (ACE) activity, established in F1 offspring from 3 weeks of age, maintained into adulthood and present also within juvenile F2 offspring. Furthermore, we observed differential expression of multiple central renin-angiotensin system regulators in adult offspring kidneys. Finally, paternal diet modified the expression profiles of central epigenetic regulators of DNA methylation, histone modifications and RNA methylation in adult F1 male testes. These novel data reveal the impact of sub-optimal paternal nutrition on offspring cardiovascular well-being, programming offspring cardiovascular function through both sperm and seminal plasma specific mechanisms over successive generations., (© 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society.)