Physiology Of Lactation Research Articles

Animal Models for In Vivo Lactation Studies: Anatomy, Physiology and Milk Compositions in the Most Used Non-Clinical Species: A Contribution from the ConcePTION Project.

Simple SummaryNowadays, the importance of breastfeeding has been very well recognized not only by the scientific world but also by public opinion. Such awareness has nonetheless put a lot of pressure on women under chronic pharmacological medication, or that simply need to alleviate common post-partum health issues, due to the lack of scientific data regarding the potential transfer to the offspring during lactation. In such a scenario, the ConcePTION project aims at creating a trusted ecosystem that can efficiently generate and disseminate reliable evidence-based information regarding the effects of medications used during pregnancy and breastfeeding to women and their healthcare providers. Due to the need for a reliable animal species to obtain scientific data, the present review summarizes the main features contributing to the lactation process in the most commonly used laboratory animal species.The present review aims to summarize the main features of mammary gland anatomy, and the physiology of lactation and colostrum/milk in the most commonly used animal species for regulatory toxicity. The final goal is the selection of a preferred animal species to be enrolled in studies investigating the potential transfer of drugs and exogenous molecules through milk, within the Innovative Medicines Initiative (IMI) funded project ConcePTION. Reference data regarding humans were also collected and analyzed in order to highlight critical similarities and differences with the studied species. Additional practical considerations were also taken into account, such as ethical consideration regarding the chosen species which affects the group size, financial implications and technical feasibility of lactation trials (e.g., ease of sampling, volume of sampling, husbandry requirements and scientific recognition). In conclusion, the present analysis of the literature confirms the complexity of the decisional process behind the choice of an animal model for in vivo trials. For some of the evaluated species, data were either poor or missing, highlighting the necessity to generate more physiological background studies for species that are routinely used in laboratory settings. Overall, when taking into consideration ethical factors, feasible group size, milk volume and ease of milk collection, and physiological similarities with humans, minipigs seem to represent the most appropriate choice.

Using animation to teach breastfeeding physiology: a proof of concept study

BackgroundBreastfeeding provides the optimal nourishment for infant and child health and supporting mothers to breastfeed is a global health priority. Midwives are uniquely placed to provide breastfeeding education and support to the woman and it is imperative that they have a sound understanding of the physiological underpinnings of breastfeeding. However, midwifery students and some midwives continue to struggle with the complex physiology of lactation. The purpose of this study was to evaluate an instructional animation resource to teach breastfeeding physiology to student and practicing midwives. Further, this study also offers insights into how student and practicing midwives accept novel approaches to learning.MethodsA cross-sectional survey design using both quantitative and qualitative approaches was employed in this proof of concept study. The setting was online with midwifery students recruited from Deakin University and registered midwives recruited from the Australian College of Midwives membership. Snowball sampling was also employed to recruit midwives through professional networks of the research team. The quantitative part of this study included a structured online questionnaire for midwives and midwifery students and descriptive statistics were used to present the quantitative data. The qualitative data were collected from open-ended questions on the questionnaire and a deductive approach was used for analysing the data.ResultsThis proof of concept study collected data from 110 participants and provides evidence for the use of animation as an effective pedagogical tool to explain complex concepts. The animated instructional resource was viewed favourably by both the midwifery students and practicing midwives.ConclusionsThe findings from this study, support the pedagogical advantages of animated instructional resources for teaching complex physiology. Further, educators should be encouraged and feel confident to develop and use animation technology as both an engaging and effective teaching resource especially for complex concepts.

Promoting and Protecting Human Milk and Breastfeeding in a COVID-19 World.

The global COVID-19 pandemic has put enormous stress on healthcare systems and hospital staffing. However, through all this, families will continue to become pregnant, give birth, and breastfeed. Unfortunately, care of the childbearing family has been de-prioritized during the pandemic. Additionally, many healthcare practices during the pandemic have not been positive for the childbearing family or breastfeeding. Despite recommendations from the World Health Organization to promote early, direct breastfeeding and skin to skin contact, these and other recommendations are not being followed in the clinical setting. For example, some mothers have been forced to go through labor and birth alone in some institutions whilst some hospitals have limited or no parental visitation to infants in the NICU. Furthermore, hospitals are discharging mothers and their newborns early, limiting the amount of time that families receive expert lactation care, education, and technical assistance. In addition, some hospitals have furloughed staff or transferred them to COVID-19 wards, further negatively impacting direct care for families and their newborns. We are concerned that these massive changes in the care of childbearing families will be permanently adopted. Instead, we must use the pandemic to underscore the importance of human milk and breastfeeding as lifesaving medical interventions. We challenge healthcare professionals to change the current prenatal and post-birth practice paradigms to protect lactation physiology and to ensure that all families in need receive equal access to evidence-based lactation education, care and technical assistance.

Maternal production of milk for infants in the neonatal intensive care unit

Mother's own milk (MOM) feeding is a cost-effective strategy to reduce risks of comorbidities associated with prematurity and improve long-term health of infants hospitalized in the Neonatal Intensive Care Unit (NICU). Significant racial and socioeconomic disparities exist in MOM provision in the NICU, highlighting the importance of developing strategies to reduce these disparities. Mothers of infants in the NICU experience many health concerns which may negatively impact lactation physiology. Objective measures of lactation physiology are limited but may assist in identifying mothers at particular risk. Several strategies to assist mothers of hospitalized infants are essential, including maternal education, qualified lactation professionals, early and frequent milk expression with a hospital-grade double electric breast pump, and providing support for transitioning to direct breastfeeding prior to discharge from the NICU.

Single Cell RNA Sequencing of Human Milk-Derived Cells Reveals Sub-Populations of Mammary Epithelial Cells with Molecular Signatures of Progenitor and Mature States: a Novel, Non-invasive Framework for Investigating Human Lactation Physiology.

Cells in human milk are an untapped source, as potential "liquid breast biopsies", of material for investigating lactation physiology in a non-invasive manner. We used single cell RNA sequencing (scRNA-seq) to identify milk-derived mammary epithelial cells (MECs) and their transcriptional signatures in women with diet-controlled gestational diabetes (GDM) with normal lactation. Methodology is described for coordinating milk collections with single cell capture and library preparation via cryopreservation, in addition to scRNA-seq data processing and analyses of MEC transcriptional signatures. We comprehensively characterized 3740 cells from milk samples from two mothers at two weeks postpartum. Most cells (>90%) were luminal MECs (luMECs) expressinglactalbumin alpha and casein beta and positive for keratin8 and keratin18. Few cells were keratin14+ basal MECs and a small immune cell population was present (<10%). Analysis of differential gene expression among clusters identified six potentially distinct luMEC subpopulation signatures, suggesting the potential for subtle functional differences among luMECs, and included one cluster that was positive for both progenitor markers and mature milk transcripts. No expression of pluripotency markers POU class 5 homeobox 1 (POU5F1,encoding OCT4) SRY-box transcription factor 2 (SOX2) or nanog homeobox (NANOG), was observed. These observations were supported by flow cytometric analysis of MECs from mature milk samples from three women with diet-controlled GDM (2-8 mo postpartum), indicating a negligible basal/stem cell population (epithelial cell adhesion molecule(EPCAM)-/integrin subunit alpha 6 (CD49f)+, 0.07%) and a small progenitor population (EPCAM+/CD49f+, 1.1%). We provide a computational framework for others and future studies, as well as report the first milk-derived cells to be analyzed by scRNA-seq. We discuss the clinical potential and current limitations of using milk-derived cells as material for characterizing human mammary physiology.

Maternal pineal melatonin in gestation and lactation physiology, and in fetal development and programming

Pregnancy and lactation are reproductive processes that rely on physiological adaptations that should be timely and adequately triggered to guarantee both maternal and fetal health. Pineal melatonin is a hormone that presents daily and seasonal variations that synchronizes the organism’s physiology to the different demands across time through its specific mechanisms and ways of action. The reproductive system is a notable target for melatonin as it actively participates on reproductive physiology and regulates the hypothalamus-pituitary-gonads axis, influencing gonadotropins and sexual hormones synthesis and release. For its antioxidant properties, melatonin is also vital for the oocytes and spermatozoa quality and viability, and for blastocyst development. Maternal pineal melatonin blood levels increase during pregnancy and triggers the maternal physiological alterations in energy metabolism both during pregnancy and lactation to cope with the energy demands of both periods and to promote adequate mammary gland development. Moreover, maternal melatonin freely crosses the placenta and is the only source of this hormone to the fetus. It importantly times the conceptus physiology and influences its development and programing of several functions that depend on neural and brain development, ultimately priming adult behavior and energy and glucose metabolism. The present review aims to explain the above listed melatonin functions, including the potential alterations observed in the progeny gestated under maternal chronodisruption and/or hypomelatoninemia.

Життєвий і творчий шлях В. А. Чаркіна — науковця, батька, дідуся

Charkin Volodymyr was PhD in Biology, Senior researcher, Head of the Laboratory of Cattle Nutrition that focuses on researching the physiology of animal lactation, studying the influence of Iodium, Chromium, Selenium, Cobalt on metabolic processes, productivity and composition of milk; development of elements of national protein feeding system of high productive cows that correspond to modern protein standardizing criteria. Lactation is a complex process of creation, storing and producing milk in animal’s mammal gland. Nervous system and hormones of endocrine glands with the help of brain cortex and hypothalamus, where lactation center is located, regulate the process of mild production. Hypothalamus produces releasing factors – somatoliberin and prolactoliberin that stimulate the production of hormones somatotropin and prolactin in hypothesis. These hormones directly take part in the production of milk. The role of other endocrine glands is that they contribute to promotion of the synthesis of milk precursors and increase of their amount in blood.

Лагодюк Петро Захарович — доктор біологічних наук, професор, академік НААН, Заслужений діяч науки і техніки України (1924–1994)

Petro Lahodyuk is the Doctor of Biological Sciences, professor, Academician of NAAS, Honourable Man of Science and Technology of Ukraine. Academician Lahodyuk was a leading researcher of animal lactation physiology. He contributed greatly into research on fraction composition and antigene properties of soluble proteins in mammary gland of open heifers, heifers and lactating cows, open and pregnant cows, compared their immune and chemical properties with milk and blood serum proteins, researched amino acidic and peptoid content of albumins in mammary gland tissues and blood serum of open heifers, heifers and cows, established the role of alveolar epithelium, excretory ducts and milk ducts in creating milk serum proteins, studied the role of a number of hormones in milk formation processes regulation, in particular regulation of milk and blood serum protein biosynthesis.

Mucosal Immunity and Liver Metabolism in the Complex Condition of Lactation Insufficiency.

Lactation insufficiency is variously defined and includes the inability to produce milk, not producing enough milk to exclusively meet infant growth requirements, and pathological interruption of lactation (e.g., mastitis). Of women with intent-to-breastfeed, lactation insufficiency has been estimated to affect 38%-44% of newly postpartum women, likely contributing to the nearly 60% of infants that are not breastfed according to the World Health Organization's guidelines. To date, research and clinical practice aimed at improving feeding outcomes have focused on hospital lactation support and education, with laudable results. However, researchers' reports of recent rodent studies concerning fundamental lactation biology have suggested that the underlying pathologies of lactation insufficiency may be more nuanced than is currently appreciated. In this article, we identify mucosal biology of the breast and lactation-specific liver biology as two under-researched aspects of lactation physiology. Specifically, we argue that further scientific inquiry into reproductive state-dependent regulation of immunity in the human breast will reveal insights into novel immune based requirements for healthy lactation. Additionally, our synthesis of the literature supports the hypothesis that the liver is an essential player in lactation-highlighting the potential that pathologies of the liver may also be associated with lactation insufficiency. More research into these biologic underpinnings of lactation is anticipated to provide new avenues to understand and treat lactation insufficiency.

Lactation after loss: supporting women's decision-making following perinatal death

Offering sensitive and compassionate clinical and bereavement care following perinatal death is the innate focus of the caring healthcare professional and facilitating informed choice around the subject of lactation following loss is an integral part of this. However, evidence suggests that there may be a deficiency in the provision of lactation advice and support following loss. Contributory factors may include a lack of awareness of lactation options following bereavement amongst midwives, as well as an absence of clarity around where the responsibility for offering lactation support and advice lies. This paper presents the literature surrounding the support of women's decision-making for lactation following perinatal death, explicating the physiology of lactation in the antenatal and postnatal periods, and exploring the challenges and opportunities for the midwife when supporting grieving mothers to decide the best option for them and their family.

Effects of fatty acids on inducing endoplasmic reticulum stress in bovine mammary epithelial cells

Fatty acids play important roles in the regulation of endoplasmic reticulum (ER) stress-induced apoptosis in different cells. Currently, the effects of fatty acids on bovine mammary epithelial cells (MEC) remain unknown. Our study examined bovine MEC viability and measured unfolded protein response (UPR)-related gene and protein expressions following fatty acid treatments. To evaluate the role of fatty acids, we treated MAC-T cells (a line of MEC) with 100 to 400 μM of saturated (palmitic and stearic acid) and unsaturated (palmitoleic, oleic, linoleic, and linolenic acid) fatty acids and 1 to 5 mM of short- and medium-chain fatty acids (acetic, propionic, butyric, and octanoic acid). Thereafter, we determined UPR-related gene expression using quantitative real-time PCR. Palmitic acid stimulated expression of XBP1s, ATF4, ATF6A, and C/EBP homologous protein (CHOP). Stearic acid increased expression of XBP1s and CHOP and decreased expression of ATF4 and ATF6A. Results of Western blot analysis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed that palmitic and stearic acid reduced MAC-T cell viability and induced extreme ER stress by increasing the protein expression of ER stress markers, such as phospho-PKR-like endoplasmic reticulum kinase, phospho-eIF2α, cleaved CASP-3, and CHOP. Among unsaturated long-chain fatty acids, palmitoleic acid increased expression of ATF4 and ATF6A. Oleic acid increased expression of XBP1s, ATF4, and ATF6A. Linoleic and linolenic acids increased expression of XBP1s, ATF4, and ATF6A but decreased expression of XBP1s and ATF6A at the highest dose. Although palmitoleic, oleic, and linoleic acid decreased CHOP expression, only palmitoleic acid increased MAC-T cell viability. Therefore, unsaturated long-chain fatty acids did not induce severe ER stress. Acetic, propionic, and butyric acids decreased expression of ATF4, ATF6A, and CHOP and increased XBP1s expression. Although only octanoic acid increased ATF4 and ATF6A expressions, it lowered expression of XBP1s and CHOP. Although fatty acid treatment did not increase the levels of ER stress proteins, butyric and octanoic acids reduced cell viability, possibly because of early differentiation. These results suggest that saturated fatty acids play important roles in MEC viability by inducing severe ER stress compared with unsaturated fatty acids. In addition, acetic and propionic acids (short- and medium-chain fatty acids) reduced ER stress. Therefore, the present study reflects the new insight that serum fatty acid concentration plays an important role in maintaining the lactation physiology of dairy cows.

Creation and validation of a visual educational technology content for lactation physiology learning.

to create and validate a visual educational technology content for lactation physiology learning. a methodological study that contemplated the stages of content creation and validation guided by the conceptual model of Knowledge Translation into action. The creation took place in partnership with the educational technology center of the project's home institution. The validation was attended by 27 judges with experience in the obstetric, neonatal, pediatric or maternal and child areas and in the theme of breastfeeding. an educational technology covered animation and video techniques to locate, respectively, elements of lactation physiology and the population involved. An Overall Content Validity Index of 0.84 was obtained. the visual educational technology for lactation physiology learning has been validated in content as a tool to introduce the theme and mediate health education actions that can have a positive impact on breastfeeding.

Musical educational technology for lactation physiology learning: knowledge translation.

create and validate a musical educational technology for lactation physiology learning for professional training in health. methodological study with application of a conceptual framework of Knowledge Translation. In the creation cycle, the knowledge of the physiology of lactation was synthetized in key points to create the lyrics and the melody. In the action cycle, the content of the musical educational technology was validated by judges experts in breast feeding, in the period from September to December 2017. 18 judges from all Brazilian regions participated in the validation. The content of the technology obtained a global Content Validity Index of 0.94 with one round of validation. the musical educational technology is validated to introduce the content of the physiology of lactation in the learning process of students, mediated by the teacher.

Variation and Interdependencies of Human Milk Macronutrients, Fatty Acids, Adiponectin, Insulin, and IGF-II in the European PreventCD Cohort.

Human milk composition is variable. The identification of influencing factors and interdependencies of components may help to understand the physiology of lactation. In this study, we analyzed linear trends in human milk composition over time, the variation across different European countries and the influence of maternal celiac disease. Within a multicenter European study exploring potential prevention of celiac disease in a high-risk population (PreventCD), 569 human milk samples were donated by women from five European countries between 16 and 163 days postpartum. Some 202 mothers provided two samples at different time points. Protein, carbohydrates, fat and fatty acids, insulin, adiponectin, and insulin-like growth factor II (IGF-II) were analyzed. Milk protein and n-6 long chain polyunsaturated fatty acids decreased during the first three months of lactation. Fatty acid composition was significantly influenced by the country of residence. IGF-II and adiponectin concentrations correlated with protein content (r = 0.24 and r = 0.35), and IGF-II also correlated with fat content (r = 0.36), suggesting a possible regulatory role of IGF in milk macronutrient synthesis. Regarding the impact of celiac disease, only the level in palmitic acid was influenced by this disease, suggesting that breastfeeding by celiac disease mothers should not be discouraged.

Optical properties of human milk.

With human milk being the most important source of infant nutrition, the protection and support of breastfeeding are essential from a global health perspective. Nevertheless, relatively few objective methods are available to investigate human milk composition and lactation physiology when a mother experiences breastfeeding problems. We argue that optics and photonics offer promising opportunities for this purpose. Any research activity within this new application field starts with a thorough understanding on how light interacts with human milk. Therefore, the aim of this study was to investigate the full set of optical properties for human milk and the biological variability therein. Using a novel approach that combines spatially resolved diffuse reflectance spectroscopy (SR-DRS) and spectroscopic optical coherence tomography (sOCT) between 450 and 650 nm, we quantified the absorption coefficient µa , scattering coefficient µs , reduced scattering coefficient µs', anisotropy g and backscattering coefficient µb,NA of mature human milk from 14 participants released at different stages during a breastfeed (foremilk, bulk milk and hindmilk). Significant correlations were found between µa , µs , µs' and µb,NA and the biochemically determined fat concentration per sample (Rs = 0.38, Rs = 0.77, Rs = 0.80, Rs = 0.44 respectively). We explained the observed variations in the optical properties of human milk using Mie theory and the biological variability in both the concentration and size distribution of milk fat globules. In conclusion, we have provided a full set of optical properties for human milk, which can hopefully serve as a starting point for future biophotonic studies on human milk and the milk containing lactating breast.

Diffuse optical spectroscopic imaging for the investigation of human lactation physiology: a case study on mammary involution.

.Relatively few imaging and sensing technologies are employed to study human lactation physiology. In particular, human mammary development during pregnancy as well as mammary involution after lactation have been poorly described, despite their importance for breast cancer diagnosis and treatment during these phases. Our case study shows the potential of diffuse optical spectroscopic imaging (DOSI) to uniquely study the spatiotemporal changes in mammary tissue composition during the involution of the lactating breast toward its pre-pregnant state. At nine time intervals over a period of eight months after the cessation of breastfeeding, we reconstructed 2-D maps of mammary water content, lipid content, total hemoglobin (THb) concentration, oxygen saturation (), and tissue optical scattering. Mammary lipid content in the nonareolar region showed a significant relative increase of 59%, whereas water content and THb concentration showed a significant relative decrease of 50% and 48%, respectively. Significant changes were also found in and tissue optical scattering. Our findings are consistent with the gradual replacement of fibroglandular tissue by adipose tissue and vascular regression during mammary involution. Moreover, our data provide unique insight into the dynamics of breast tissue composition and demonstrate the effectiveness of DOSI as a technique to study human lactation physiology.

Cutaneous perfusion of the human lactating breast: a pilot study with laser Doppler perfusion monitoring

Objective: Knowledge on the hemodynamics of the human lactating breast contributes to our understanding of lactation physiology, as well as the development and management of breastfeeding problems. The objective of this pilot study was to investigate whether laser Doppler perfusion monitoring (LDPM) can be employed to measure physiological changes in mammary cutaneous perfusion during milk extraction. Approach: We evaluated mammary cutaneous perfusion with LDPM in nine lactating women during milk extraction in both the ipsilateral (‘milk extracting’) and contralateral (‘passive’) breast. Fourier domain filtering of the LDPM signal was applied to correct for the influence of the periodic tissue movement caused by the breast pump. Main results: Cutaneous perfusion increased temporary during 23.7 ± 18.9 s by 18%–74% for all women who sensed their milk ejection reflex (n = 6) in both the ipsilateral and contralateral breast. For those women who did not sense a milk ejection reflex (n = 3), the changes in cutaneous perfusion were less outspoken (maximally 26%). Significance: This pilot study provides new insights into mammary hemodynamics and demonstrates that LDPM is a promising method for the further investigation of physiological changes in mammary cutaneous perfusion during milk ejection. Objective feedback on the occurrence and progression of milk ejection can support lactation research in general, maternal breastfeeding confidence, and may be an early indicator for the development of breastfeeding problems.

Transcriptome Analysis of Dairy Goat Mammary Gland Tissues from Different Lactation Stages.

The mammary gland is a unique organ involved in lactation in dairy livestock, and its development and lactation ability are affected by both genetic and environmental factors. To explore the molecular regulatory mechanisms of these factors, this study used high-throughput sequencing technology and bioinformatics methods to systematically analyze the transcriptome of Laoshan dairy goat mammary gland tissues from different lactation stages. From three libraries, 36,336,892, 36,469,596, and 35,759,380, pure sequences were obtained, with 25,292, 23,665 and 27,220 expressed genes, respectively, resulting in a total of 14,892 nonredundant differentially expressed genes. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that these genes were annotated to biological regulation, cellular processes, metabolic processes, cells, organelles, binding, catalytic activity and transcriptional activity, and so on. The genes were mainly involved in cellular processes, environmental information processes, genetic information processes, human diseases, metabolism, and organ systems. Finally, 20 genes related to mammary gland development and lactation were screened to construct a gene regulatory network. These findings support the involvement of the constructed network in the regulation of mammary gland development and lactation, and they not only lay the foundation to further investigate and screen the main genes or molecular genetic markers controlling the development of the mammary gland and lactation ability of dairy goats but also increase the in-depth understanding of the lactation physiology of dairy goats.

Eficácia de intervenções educativas com gestantes sobre o grau de conhecimento em aleitamento materno

Objective: To evaluate the level of knowledge about breastfeeding in women in the first half of pregnancy receiving prenatal care through the Unified Health System (Sistema Unico de Saude – SUS) and carry out health education activities on this subject with the aim of improving pregnant women’s level of knowledge. Methods: This longitudinal intervention study was conducted at the Primary Health Care (PHC) centers of Limoeiro do Norte, Ceara, Brazil with 57 women in the first half of pregnancy. Socioeconomic information on education, ethnicity, professional activity, household income, and marital status was collected and knowledge of four breastfeeding-related thematic blocks was evaluated: prenatal breast care, advantages of breastfeeding for the mother-child binomial. child, lactation physiology and appropriate breastfeeding techniques. Subsequently, four educational interventions were carried out on a weekly basis either in the PHC centers or at home focusing on the four approaches described in the form. The knowledge evaluation instrument was then reapplied. Results: Pregnant women’s level of knowledge improved in all the domains of breastfeeding analyzed: from 62.8% to 83.0% of correct answers in thematic block one (range: 20.2%); from 71.6% to 87.5% in block two (15.9%); from 66.9% to 79.7% in block three (12.7%); from 63.6% to 92.6% in block four (29.0%). There was a greater impact on “adequate breastfeeding techniques”. Conclusion: Pregnant women had adequate knowledge about most questions about breastfeeding. Health education was effective in improving such knowledge, which in the future may reflect on the prolongation of exclusive breastfeeding duration. Registration Number (ReBEC): RBR-3rs7sx

ФИЗИОЛОГИЯ И ПАТОЛОГИЯ ЛАКТАЦИИ

ФИЗИОЛОГИЯ И ПАТОЛОГИЯ ЛАКТАЦИИ