Late gestation hyperthermia: epigenetic programming of daughter's mammary development and function

Abstract Improvements in modern sow prolificacy have markedly increased the number of pigs weaned, thus the ability of sows to provide nutrients to support fetal growth and milk production has been enhanced. The goals of the gestation nutrition program consist of meeting the nutrient requirements for maintenance and growth and for adequate conceptus development, while managing body condition. Early gestation represents the best opportunity for replenishing body reserves, whereas in late gestation, both estimated protein deposition and energy requirement are exponentially increased and directed towards fetal growth and mammary development. Increased feed intake after breeding has been presumed to be detrimental to embryo survival; however, data with modern line sows demonstrates to feed thin sows to recover body condition as quickly as possible while avoiding feed deprivation immediately after breeding. Importance of body condition scoring remains unchanged: feed thin sows to bring back to adequate body condition and prevent over-conditioned sows at farrowing. A recent meta-analysis showed increasing late gestation feed intake seems to modestly improve piglet birth weight by 28 g per piglet in gilts and sows. Also, recent findings in gestating sows suggest modern genotypes have improved feed efficiency and propensity for growth. Therefore, increasing energy intake during late gestation has a modest effect on piglet birth weight and a negative effect on stillborn rate. Historically, lactation catabolism impacted subsequent reproductive performance of sows, particularly in first-parity. However, contemporary sows appear to be increasingly resistant to the negative effects of lactational catabolism. Even so, continued emphasis on maximizing lactation feed intake is critical to support milk production and prevent excessive lean tissue mobilization. Research data suggests that ad libitum feeding and offering lactation diets during the wean-to-estrus interval is not needed. Modern genetic sow lines appear to be more robust from a nutritional perspective than in the past.

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Fibroblasts and mesenchymal cells

Oxford Textbook of Rheumatology ◽

10.1093/med/9780199642489.003.0051 ◽

2013 ◽

pp. 379-385

Author(s):

Andrew Filer ◽

Maria Juarez ◽

Christopher Buckley

Keyword(s):

Rheumatoid Arthritis ◽

Wound Healing ◽

Joint Destruction ◽

Joint Inflammation ◽

Synovial Fibroblasts ◽

Mesenchymal Cells ◽

Structure And Function ◽

Epigenetic Programming ◽

Disease Initiation ◽

And Function

In order to understand and explore the function and roles of fibroblasts, it is necessary to understand their lineage relationships to other mesenchymal cells. Fibroblasts are ubiquitous non-epithelial, non-endothelial, and non-haematopoietic adherent cells that have the capacity to produce and remodel extracellular matrix. In addition to their well-known ’landscaping’ function which determines the unique structure and function of different organs, they play an important role in wound healing, immune tolerance, and disease. In cancer, epithelial-stromal interactions have been implicated in disease initiation and progression. In rheumatoid arthritis, synovial fibroblasts at diseased sites become persistently activated and behave abnormally, orchestrating joint inflammation and contributing to joint destruction. Recent evidence suggests that the activated phenotype of fibroblasts in pathology may result from epigenetic programming, which is becoming a major focus for development of new therapeutics.

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Chronic maternal inflammation during late gestation impairs subsequent β-cell function but not islet growth in fetal sheep

Translational Animal Science ◽

10.1093/tas/txy080 ◽

2018 ◽

Vol 2 (suppl_1) ◽

pp. S99-S99

Author(s):

M D Abebe ◽

C N Cadaret ◽

T B Barnes ◽

K A Beede ◽

D T Yates

Keyword(s):

Blood Glucose ◽

Plasma Insulin ◽

Physical Development ◽

Late Gestation ◽

Strong Positive Correlation ◽

Β Cell ◽

Fetal Pancreas ◽

Arterial Blood ◽

And Function ◽

And Control

Abstract Intrauterine growth restriction (IUGR) greatly increases perinatal mortality and morbidity rates, and leads to much greater risk for metabolic complications later in life. One such complication is the development of glucose intolerance or diabetes, which typically develops concurrently with abhorrent patterns of insulin secretions due to diminished β-cell mass and impaired function as well as an overall reduction in pancreatic endocrine tissue. The mechanisms by which IUGR causes problems with health and function of the pancreatic islets are not well understood. Therefore, our goal for this study was to determine how materno-fetal inflammation (MI) affects β-cell growth and function. To do this, we compared the average islet areas, plasma insulin concentrations, and blood glucose concentrations between MI-IUGR fetal lambs (n = 7) and control fetal lambs (n = 7). Pregnant ewes were injected with saline (controls) or 0.1-µg/kg bacterial lipopolysaccharide (LPS) every 3 d from days 100 to 115 of gestation (term = 150 d). Throughout late gestation, arterial blood of the fetus was periodically drawn and analyzed for plasma insulin (ELISA) and blood glucose (ABL90 FLEX) levels. On day 125 of gestation, ewes were euthanized and fetal pancreas was extracted. Sections of the fetal pancreas were then fixed in 4% paraformaldehyde, sectioned (cryostat) at a thickness of 8 µm, stained for insulin-positive area, and imaged on 20x magnification for analysis of average islet area. Between MI-IUGR and control fetuses, there were no differences in average islet areas (1675 ± 286 and 1678 ± 287 µm2, respectively), which indicates that MI did not impair growth and physical development of fetal islets. In addition, blood glucose was similar in all fetuses. However, results showed less (P ≤ 0.05) plasma insulin concentration in MI-IUGR fetuses (0.39 ± 0.07 ng/mL) than in controls (0.70 ± 0.09 ng/mL). This indicates impaired β-cell functional capacity in MI-IUGR fetuses despite normal growth, which is quantified by a tendency (P = 0.08) for strong positive correlation (r = 0.91) between plasma insulin and islet area in control fetuses but an absence of correlation in MI-IUGR fetuses. From this study, we can conclude that MI-IUGR has no effect on the growth and physical development of β cells; however, it does greatly affect their function.

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Review: Mammary development in swine: effects of hormonal status, nutrition and management

Canadian Journal of Animal Science ◽

10.4141/cjas2012-066 ◽

2013 ◽

Vol 93 (1) ◽

pp. 1-7 ◽

Cited By ~ 13

Author(s):

C. Farmer

Keyword(s):

Detrimental Effect ◽

Current Knowledge ◽

Management Strategies ◽

Mammary Development ◽

Late Gestation ◽

Mammary Tissue ◽

Hormonal Status ◽

Best Management ◽

Lactating Sows ◽

Endocrine Status

Farmer, C. 2013. Review: Mammary development in swine: effects of hormonal status, nutrition and management. Can. J. Anim. Sci. 93: 1–7. There are three phases of rapid mammary accretion in swine, namely, from 90 d of age until puberty, during the last third of gestation and throughout lactation. Nutrition, endocrine status and management of gilts or sows during those periods can affect mammary development. More specifically, in growing gilts, feed restriction as of 90 d of age hinders mammary development and either supplying the phytoestrogen genistein or increasing circulating concentrations of prolactin stimulates mammogenesis. In late gestation, inhibition of relaxin or prolactin drastically diminishes mammary development and overly increasing dietary energy has a detrimental effect on mammogenesis. It also appears that feeding of the gestating sow can affect the mammary development of her offspring once it reaches puberty. Various management factors such as litter size, nursing intensity and use or non-use of a teat in the previous lactation will affect the amount of mammary tissue present at the end of lactation. Mammary development is followed by the essential process of involution whereby a rapid and drastic regression in parenchymal tissue takes place. It can occur either after weaning or in early lactation when teats are not being regularly suckled. Despite our current knowledge, much remains to be learned in order to develop the best management strategies for replacement gilts, and gestating and lactating sows that will maximize their milk production.

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Effects of sustained hyperprolactinemia in late gestation on mammary development of gilts

Domestic Animal Endocrinology ◽

10.1016/j.domaniend.2019.106408 ◽

2020 ◽

Vol 72 ◽

pp. 106408 ◽

Cited By ~ 1

Author(s):

A. Caron ◽

M.F. Palin ◽

R.C. Hovey ◽

J. Cohen ◽

J.P. Laforest ◽

...

Keyword(s):

Mammary Development ◽

Late Gestation

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Functional consequence of exposure to dieldrin on mammary development and function

Food Additives & Contaminants ◽

10.1080/0265203031000138231 ◽

2003 ◽

Vol 20 (9) ◽

pp. 819-828 ◽

Cited By ~ 9

Author(s):

C. Tarraf ◽

M. El-Sabban ◽

R. Bassam ◽

M. Beyrouthy ◽

J. Chamoun ◽

...

Keyword(s):

Mammary Development ◽

Functional Consequence ◽

And Function

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Bioinformatics and Gene Network Analyses of the Swine Mammary Gland Transcriptome during Late Gestation

Bioinformatics and Biology Insights ◽

10.4137/bbi.s12205 ◽

2013 ◽

Vol 7 ◽

pp. BBI.S12205 ◽

Cited By ~ 9

Author(s):

Wangsheng Zhao ◽

Khuram Shahzad ◽

Mingfeng Jiang ◽

Daniel E. Graugnard ◽

Sandra L. Rodriguez-Zas ◽

...

Keyword(s):

Network Analysis ◽

Receptor Binding ◽

Gene Network ◽

Fatty Acid Biosynthesis ◽

Mammary Development ◽

Late Gestation ◽

Interleukin 4 ◽

Receptor Interaction ◽

Bioinformatics Analyses ◽

Network Analyses

We used the newly-developed Dynamic Impact Approach (DIA) and gene network analysis to study the sow mammary transcriptome at 80, 100, and 110 days of pregnancy. A swine oligoarray with 13,290 inserts was used for transcriptome profiling. An ANOVA with false discovery rate (FDR < 0.15) correction resulted in 1,409 genes with a significant time effect across time comparisons. The DIA uncovered that Fatty acid biosynthesis, Interleukin-4 receptor binding, Galactose metabolism, and mTOR signaling were among the most-impacted pathways. IL-4 receptor binding, ABC transporters, cytokine-cytokine receptor interaction, and Jak-STAT signaling were markedly activated at 110 days compared with 80 and 100 days. Epigenetic and transcription factor regulatory mechanisms appear important in coordinating the final stages of mammary development during pregnancy. Network analysis revealed a crucial role for TP53, ARNT2, E2F4, and PPARG. The bioinformatics analyses revealed a number of pathways and functions that perform an irreplaceable role during late gestation to farrowing.

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Food intake dependent and independent effects of heat stress on lactation and mammary gland development

10.1101/2020.04.03.024679 ◽

2020 ◽

Author(s):

Yao Xiao ◽

Jason M. Kronenfeld ◽

Benjamin J. Renquist

Keyword(s):

Heat Stress ◽

Mammary Gland ◽

Food Intake ◽

Milk Production ◽

Mammary Gland Development ◽

Heat Exposure ◽

Mammary Development ◽

Late Gestation ◽

Independent Effects ◽

Gland Development

ABSTRACTWith a growing population, a reliable food supply is increasingly important. Heat stress reduces livestock meat and milk production. Genetic selection of high producing animals increases endogenous heat production, while climate change increases exogenous heat exposure. Both sources of heat exacerbate the risk of heat-induced depression of production. Rodents are valuable models to understand mechanisms conserved across species. Heat exposure suppresses feed intake across homeothermic species including rodents and production animal species. We assessed the response to early-mid lactation or late gestation heat exposure on milk production and mammary gland development/function, respectively. Using pair-fed controls we experimentally isolated the food intake dependent and independent effects of heat stress on mammary function and mass. Heat exposure (35°C, relative humidity 50%) decreased daily food intake. When heat exposure occurred during lactation, hypophagia accounted for approximately 50% of the heat stress induced hypogalactia. Heat exposure during middle to late gestation suppressed food intake, which was fully responsible for the lowered mammary gland weight of dams at parturition. However, the impaired mammary gland function in heat exposed dams measured by metabolic rate and lactogenesis could not be explained by depressed food consumption. In conclusion, mice recapitulate the depressed milk production and mammary gland development observed in dairy species while providing insight regarding the role of food intake. This opens the potential to apply genetic, experimental and pharmacological models unique to mice to identify the mechanism by which heat is limiting animal production.Summary StatementsThis study demonstrates that heat stress decreases lactation and mammary development through food intake dependent and independent mechanisms.

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