Importance of the lactation period in developmental programming in rodents

2020 ◽  
Vol 78 (Supplement_2) ◽  
pp. 32-47 ◽  
Author(s):  
Guadalupe L Rodríguez-González ◽  
Claudia J Bautista ◽  
Karen I Rojas-Torres ◽  
Peter W Nathanielsz ◽  
Elena Zambrano

Abstract Lactation is a critical period during which maternal nutritional and environmental challenges affect milk composition and, therefore, organ differentiation, structure, and function in offspring during the early postnatal period. Evidence to date shows that lactation is a vulnerable time during which transient insults can have lasting effects, resulting in altered health outcomes in offspring in adult life. Despite the importance of the developmental programming that occurs during this plastic period of neonatal life, there are few comprehensive reviews of the multiple challenges—especially to the dam—during lactation. This review presents milk data from rodent studies involving maternal nutritional challenges and offspring outcome data from studies involving maternal manipulations during lactation. Among the topics addressed are maternal nutritional challenges and the effects of litter size and artificial rearing on offspring metabolism and neural and endocrine outcomes. The lactation period is an opportunity to correct certain functional deficits resulting from prenatal challenges to the fetus, but, if not personalized, can also lead to undesirable outcomes related to catch up-growth and overnutrition.

Author(s):  
Parul Christian ◽  
Emily R Smith ◽  
Sun Eun Lee ◽  
Ashley J Vargas ◽  
Andrew A Bremer ◽  
...  

ABSTRACT Critical advancement is needed in the study of human milk as a biological system that intersects and interacts with myriad internal (maternal biology) and external (diet, environment, infections) factors and its plethora of influences on the developing infant. Human-milk composition and its resulting biological function is more than the sum of its parts. Our failure to fully understand this biology in a large part contributes to why the duration of exclusive breastfeeding remains an unsettled science (if not policy). Our current understanding of human-milk composition and its individual components and their functions fails to fully recognize the importance of the chronobiology and systems biology of human milk in the context of milk synthesis, optimal timing and duration of feeding, and period of lactation. The overly simplistic, but common, approach to analyzing single, mostly nutritive components of human milk is insufficient to understand the contribution of either individual components or the matrix within which they exist to both maternal and child health. There is a need for a shift in the conceptual approach to studying human milk to improve strategies and interventions to support better lactation, breastfeeding, and the full range of infant feeding practices, particularly for women and infants living in undernourished and infectious environments. Recent technological advances have led to a rising movement towards advancing the science of human-milk biology. Herein, we describe the rationale and critical need for unveiling the multifunctionality of the various nutritional, nonnutritional, immune, and biological signaling pathways of the components in human milk that drive system development and maturation, growth, and development in the very early postnatal period of life. We provide a vision and conceptual framework for a research strategy and agenda to change the field of human-milk biology with implications for global policy, innovation, and interventions.


2020 ◽  
pp. jrheum.191004
Author(s):  
Noortje Groot ◽  
Anne Kardolus ◽  
Marc Bijl ◽  
Radboud Dolhain ◽  
Onno Teng ◽  
...  

Objective Long-term outcome data in adults with childhood-onset SLE are limited. Here, we report the effects of cSLE on education, vocation and employment in a large cohort of adults with cSLE. Methods Patients were seen for a single study visit containing a structured history and physical examination. Medical records were retrieved to supplement information obtained during the study visit. Education and employment status were assessed by questionnaires. Health-related quality of life (HRQOL) was measured with the SF36. Results 106 cSLE patients (93% female, 73% white), with a median disease duration of 20 years, completed the visit and questionnaires. Almost all patients stated that cSLE had influenced their education, but level of completed education was similar to the general Dutch population. Half of the patients had adjusted their vocational choice due to the disease. Still, 44% of patients who had finished education did not have a paid job. Of the employed patients, 61% worked part-time. Disease damage was equally prevalent in patients with and without paid employment. A high percentage of patients (51%) were declared work disabled, which was related to damage. Patients who did not have paid employment were often work disabled. Both had a negative influence on HRQOL. Conclusion The effect of cSLE on academic achievements and employment is substantial, despite adjusting educational and vocational choices to the disease. Ongoing support, not only to help patients find suitable education and vocation, but also to offer guidance regarding potential adjustments during their career, is necessary to optimise participation in the community.


2019 ◽  
Vol 29 (4) ◽  
pp. 467-474 ◽  
Author(s):  
Zahra Hoodbhoy ◽  
Nuruddin Mohammed ◽  
Nadeem Aslam ◽  
Urooj Fatima ◽  
Salima Ashiqali ◽  
...  

AbstractObjective:The objective of this study was to assess differences in myocardial systolic and diastolic function and vascular function in children 2−5 years of age born to diabetic as compared to non-diabetic mothers.Methods:This study was a retrospective cohort conducted in 2016 at The Aga Khan University Hospital, Karachi, Pakistan. It included children between 2 and 5 years of age born to mothers with and without exposure to diabetes in utero (n = 68 in each group) and who were appropriate for gestational age. Myocardial morphology and function using echocardiogram and carotid intima media thickness (cIMT) and pulse wave velocity was performed to evaluate cardiac function as well as macrovascular remodelling in these children. Multiple linear regression was used to compare the groups.Results:There was no significant difference in cardiac morphology, myocardial systolic and diastolic function, and macrovascular assessment between the exposed and unexposed groups of AGA children. Subgroup analysis demonstrated a significantly decreased mitral E/A ratio in children whose mothers were on medications as compared to those on dietary control (median [IQR] = 1.7 [1.6–1.9] and 1.56 [1.4–1.7], respectively, p = 0.02), and a higher cIMT in children whose mothers were on medication as compared to controls (0.48 [0.44–0.52] and 0.46 [0.44–0.50], respectively, p = 0.03).Conclusion:In utero exposure to uncontrolled maternal diabetes has an effect on the cardiovascular structure and function in children aged 2−5 years. However, future work requires long-term follow-up from fetal to adult life to assess these changes over the life course.


Author(s):  
Analia Lorena Tomat ◽  
Francisco Javier Salazar

AbstractA substantial body of epidemiological and experimental evidence suggests that a poor fetal and neonatal environment may “program” susceptibility in the offspring to later development of cardiovascular, renal and metabolic diseases.This review focuses on current knowledge from the available literature regarding the mechanisms linking an adverse developmental environment with an increased risk for cardiovascular, renal and metabolic diseases in adult life. Moreover, this review highlights important sex-dependent differences in the adaptation to developmental insults.Developmental programming of several diseases is secondary to changes in different mechanisms inducing important alterations in the normal development of several organs that lead to significant changes in birth weight. The different diseases occurring as a consequence of an adverse environment during development are secondary to morphological and functional cardiovascular and renal changes, to epigenetic changes and to an activation of several hormonal and regulatory systems, such as angiotensin II, sympathetic activity, nitric oxide, COX2-derived metabolites, oxidative stress and inflammation. The important sex-dependent differences in the developmental programming of diseases seem to be partly secondary to the effects of sex hormones. Recent studies have shown that the progression of these diseases is accelerated during aging in both sexes.The cardiovascular, renal and metabolic diseases during adult life that occur as a consequence of several insults during fetal and postnatal periods are secondary to multiple structural and functional changes. Future studies are needed in order to prevent the origin and reduce the incidence and consequences of developmental programmed diseases.


2005 ◽  
Vol 99 (1) ◽  
pp. 114-119 ◽  
Author(s):  
David F. Donnelly ◽  
Insook Kim ◽  
Claire Carle ◽  
John L. Carroll

Hyperoxia in the immediate perinatal period, but not in adult life, is associated with a life-long impairment of the ventilatory response to acute hypoxia. This effect is attributed to a functional impairment of peripheral chemoreceptors, including a reduction in the number of chemoreceptor afferent fibers and a reduction in “whole nerve” afferent activity. The purpose of the present study was to assess the activity levels of single chemoreceptor units in the immediate posthyperoxic period to determine whether functional impairment extended to single chemoreceptor units and whether the impairment was only induced by hyperoxia exposure in the immediate postnatal period. Two groups of rat pups were exposed to 60% inspired O2 fraction for 2 wk at ages 0–14 days and 14–28 days, at which time single-unit activities were isolated and recorded in vitro. Compared with control pups, hyperoxia-treated pups had a 10-fold reduction in baseline (normoxia) spiking activity. Peak unit responses to 12, 5, and 0% O2 were reduced and nerve conduction time was significantly slower in both hyperoxia-treated groups compared with control groups. We conclude that 1) hyperoxia greatly reduces single-unit chemoreceptor activities during normoxia and acute hypoxia, 2) the treatment effect is not limited to the immediate newborn period, and 3) at least part of the impairment may be due to changes in the afferent axonal excitability.


2019 ◽  
Vol 59 (3) ◽  
pp. 461 ◽  
Author(s):  
Angelisa H. Biazus ◽  
Chrystian J. Cazarotto ◽  
Gustavo Machado ◽  
Nathieli B. Bottari ◽  
Mariana S. Alves ◽  
...  

Diphenyl diselenide ((PhSe)2) is a organoselenium compound with potent antioxidant properties. Therefore, the aim of the present study was to evaluate whether subcutaneous supplementation of (PhSe)2 in dairy sheep has positive effects on milk composition, as well as on the prevention of oxidative stress and exacerbated inflammatory response. For this, 16 primiparous recently calved sheep were divided into the following two groups, with eight animals in each: Group A, the control group; and Group B, the group subcutaneously supplemented with five doses of (PhSe)2 of 3.0µmol/kg each every 7 days. Blood samples from supplemented animals showed increased concentration of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase and glutathione-S-transferase), and reduced reactive oxygen species and lipid peroxidation, which prevented oxidative damage in the lactation period, as well as increased seric interleukin-10, an anti-inflammatory cytokine. In the sera, supplemented animals showed increased total antioxidant capacity and ferric-reducing ability of plasma compared with the control group. As a consequence, supplemented animals showed increased antioxidant variables, as well as reduced protein oxidation in milk samples. Moreover, milk from supplemented sheep showed a higher fat content, and lower total protein and lactose contents in some periods in the study, than did not-supplemented ewes. Seric concentrations of interleukin-1 were lower on Days 30 and 45 in supplemented animals, as well as the concentrations of tumour necrosis factor α in all periods, than were those in the control group, whereas the interleukin-10 concentrations were higher. Thus, dairy sheep supplementation of (PhSe)2 activated antioxidant and anti-inflammatory responses, and increased milk fat content. Moreover, this protocol increased the antioxidant and, consequently, reduced the oxidant concentration in milk, which is desirable for product quality.


2017 ◽  
pp. 273-280.e3 ◽  
Author(s):  
Donna Geddes ◽  
Foteini Hassiotou ◽  
Michael Wise ◽  
Peter Hartmann

Author(s):  
Caroline Fall ◽  
Kalyanaraman Kumaran

Sub-optimal nutrition during foetal and infant development is associated with an increased risk of non-communicable diseases (NCDs) in adult life. Animal experiments show that this results from permanent effects on the structure and function of tissues and hormone systems (‘metabolic programming’), probably mediated by epigenetic changes. NCD risk is increased further by adiposity and/or unhealthy lifestyles in childhood or adulthood. Apart from nutrition, other early life environmental influences can programme later disease, including foetal ‘over-nutrition’ (maternal diabetes or obesity) and exposure to maternal smoking, environmental pollutants, and pregnancy complications. The concept that improving the nutrition and health of mothers pre-conceptionally and during pregnancy could prevent common NCDs has huge public health implications. However, unlike the robust demonstration of programming in experimental animals, the evidence in humans rests mainly on observational research. Intervention studies are ongoing to strengthen the evidence and to identify ways to improve early development and prevent NCDs.


2013 ◽  
Vol 4 (4) ◽  
pp. 269-279 ◽  
Author(s):  
A. M. Vaiserman

A growing body of evidence highlights the importance of the nutritional or other environmental stimuli during critical periods of development in the long-term programming of organ systems and homeostatic pathways of the organism. The adverse influences early in development and particularly during intrauterine life have been shown to programme the risks for adverse health outcomes in adult life. The mechanisms underlying developmental programming remain still unclear. However, increasing evidence has been accumulated indicating the important role of epigenetic regulation including DNA methylation, histone modifications and non-coding RNAs in the developmental programming of late-onset pathologies, including cancer, neurodegenerative diseases, and type 2 diabetes. The maternal substance abuse during pregnancy, including smoking, drinking and psychoactive drug intake, is one of the important factors determining the process of developmental programming in modern human beings. The impact of prenatal drug/substance exposure on infant and early childhood development is currently in the main focus. The long-term programming effects of such exposures on aging and associated pathologies, however, have been reported only rarely. The purpose of this review is to provide a summary of recent research findings which indicate that maternal substance abuse during pregnancy and/or neonatal period can programme not only a child's health status, but also can cause long-term or even life-long health outcomes via mechanisms of epigenetic memory.


Reproduction ◽  
2018 ◽  
Vol 156 (2) ◽  
pp. R23-R42 ◽  
Author(s):  
Lindsay Ellsworth ◽  
Emma Harman ◽  
Vasantha Padmanabhan ◽  
Brigid Gregg

The window of lactation is a critical period during which nutritional and environmental exposures impact lifelong metabolic disease risk. Significant organ and tissue development, organ expansion and maturation of cellular functions occur during the lactation period, making this a vulnerable time during which transient insults can have lasting effects. This review will cover current literature on factors influencing lactational programming such as milk composition, maternal health status and environmental endocrine disruptors. The underlying mechanisms that have the potential to contribute to lactational programming of glucose homeostasis will also be addressed, as well as potential interventions to reduce offspring metabolic disease risk.


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