Onset Of Lactation Research Articles

Liver transcriptome analysis reveals important factors involved in the metabolic adaptation of the transition cow

During early lactation, dairy cows experience a severe metabolic load often resulting in the development of various diseases. The inevitable deficiency in nutrients and energy at the onset of lactation requires an optimal adaptation of the hepatic metabolism to overcome metabolic stress. We conducted a whole-liver transcriptome analysis for the transition cow to identify novel factors crucial for metabolic adaptation. Liver samples were obtained from 6 Red Holstein dairy cows (parity 2 to 7, mean ± standard deviation: 3.7 ± 2.3) at 3 time points: T1 = 22 ± 4 d antepartum, T2 = 10 ± 2 d postpartum, and T3 = 17 ± 2 d postpartum. Using RNA sequencing (RNA-seq), we studied the transcriptomic profile of the transition cow before and after parturition. We performed a differential gene expression analysis (DGEA) and gene-set enrichment analysis (GSEA) for biological processes (gene ontology, GO) and pathways (Kyoto Encyclopedia of Genes and Genomes, KEGG). Among the 10,186 expressed genes, we discovered 1,063 differentially expressed genes (false discovery rate = 5%). The GSEA revealed 16 biological processes and 7 pathways significantly (false discovery rate = 5%) associated with the hepatic changes of the transition cow. Our results confirm that major hepatic changes are related to energy mobilization after parturition; in particular, they are related to fatty acid oxidation/metabolism, cholesterol metabolism, and gluconeogenesis. Using the STRING database (https://string-db.org/), we investigated interactions between significant genes and identified 9 key genes (CYP7A1, APOA1, CREM, LOC522146, CYP2C87, HMGCR, FDFT1, SGLE, and CYP26A1) through which the different processes involved in the metabolic adaptation interact. Comparing our main results with the literature, we could identify further genes that have not yet been associated with the transition period (e.g., CPT1B, ADIPOR2, LEPR, CREB3L3, and CCND1) and that are mainly involved in processes controlled by AMP-activated protein kinase, an important regulator of energy homeostasis.

Ethyl-cellulose rumen-protected methionine enhances performance during the periparturient period and early lactation in Holstein dairy cows

The onset of lactation in dairy cows is characterized by severe negative energy and protein balance. Increasing Met availability during this time may improve milk production, hepatic lipid metabolism, and immune function. The aim of this study was to evaluate the effect of feeding ethyl-cellulose rumen-protected methionine (RPM; Mepron, Evonik Nutrition and Care GmbH, Hanau-Wolfgang, Germany) on the performance of dairy cows during prepartum and early-lactation periods. Sixty multiparous Holstein cows were used in a block design and assigned to either a control or an ethyl-cellulose RPM diet. Ethyl-cellulose RPM was supplied from -28 to 60 d relative to parturition at a rate of 0.09% and 0.10% of dry matter during the prepartum and postpartum periods, respectively. That rate ensured that the ratio of Lys to Met in metabolizable protein was close to 2.8:1. Cows fed ethyl-cellulose RPM had dry matter intakes (DMI) that were 1.2 kg/d greater during the prepartum period and consequently had overall greater cumulative DMI than cows in the control group. Compared with controls, during the fresh period (1-30 d in milk; DIM) feeding ethyl-cellulose RPM increased DMI by 1.7 kg/d, milk yield by 4.1 kg/d, fat yield by 0.17 kg/d, milk protein yield by 0.20 kg/d, 3.5% fat-corrected milk by 4.3 kg/d, and energy-corrected milk by 4.4 kg/d. Although ethyl-cellulose RPM supplementation increased milk protein content by 0.16 percentage units compared with the control during the fresh period, no differences were observed for milk fat, lactose, and milk urea nitrogen concentration. During the high-producing period (31-60 DIM), cows fed ethyl-cellulose RPM increased DMI and milk yield by 1.45 and 4.4 kg/d, respectively. Ethyl-cellulose RPM also increased fat yield by 0.19 kg/d, milk protein yield by 0.17 kg/d, 3.5% fat-corrected milk by 4.7 kg/d, and energy-corrected milk by 4.8 kg/d compared with controls. Ethyl-cellulose RPM supplementation reduced plasma fatty acids in the fresh period and decreased γ-glutamyl transferase, indicating better liver function. In conclusion, when lysine was adequate, feeding ethyl-cellulose RPM to achieve a ratio close to 2.8:1 in metabolizable protein improved dairy cow performance from parturition through 60 DIM. The greater milk production was, at least in part, driven by the greater voluntary DMI and better liver function.

Current situation and influencing factors of maternal breastfeeding after the childbirth

Objective To investigate the current situation of maternal breastfeeding after the childbirth in Shanghai and analyze its influencing factors, so as to improve breastfeeding. Methods In this study, longitudinal follow-up and questionnaire designed based on the hospital were carried out on pregnant women at the outpatient department in eight baby-friendly hospitals of Shanghai from October 2015 to January 2016. The questionnaires included demographic characteristics and their prospective feeding method after the childbirth. Pregnant women were followed up until the delivery was finished. At the time of hospitalization discharge, they were given the 2nd questionnaire containing the basic situation after the delivery and the actual breastfeeding behavior situation. Results The rates of pregnant women with the intention of breastfeeding and exclusive breastfeeding during the third trimester were 82.5% and 82.3% respectively. After the delivery, 56.4% (399/707) of mothers were breastfeeding. Binary logistic regression analysis showed that, for primipara group, breastfeeding behavior after the delivery was related to five factors: the breastfeeding intention in third trimester, age, household register, the time of onset of lactation and whether the baby was in the care unit; for multiparas group, breastfeeding behavior was related to two factors: the time of onset of lactation and whether the baby was in the care unit. Conclusions Health care workers should attach importance to the promotion of breastfeeding during pregnancy for primipara group and pay attention to the health education of the mothers with registered permanent residence of Shanghai. During the hospitalization, health care workers should strictly implement the sucking, early contact as the baby-friendly hospital required, strengthen the breastfeeding knowledge and skill training for mothers whose babies are in the maternal care unit, ensure the normal lactation of mothers without their babies so as to improve the early breast-feeding rate after the delivery. Key words: Breastfeeding; Exclusive breastfeeding; Behavior intention; Late pregnancy

Abstract 4993: The role of super-enhancers and genetic boundaries in gene regulation

Abstract The purpose of this study was to investigate the role of the Zn finger protein CTCF in the establishment of genetic borders and in controlling spatially-restricted activity of a mammary-specific super-enhancer (SE) known to selectively activate gene expression during pregnancy. CRISPR/Cas9 gene editing was used to generate mice with deletions in CTCF binding sites (CBSs) separating the Wap SE from the Ramp3 gene. ChIP-seq and qRT-PCR were used to investigate protein-DNA interactions and changes in gene expression, respectively. RNA-seq data demonstrated that expression of the mammary-specific Wap and widely-expressed Ramp3 gene was activated in mammary tissue at the onset of lactation. To investigate the possibility that the Wap SE can regulate both genes, mice carrying deletions in the SE were established. In these mice, both Wap and downstream Ramp3 were downregulated to the same extent, supporting the notion that the SE regulates both genes. Given these results, we investigated the contributions of several intervening CBSs in dampening SE activity on Ramp3. Mice harboring individual and combinatorial deletions of three CBSs (A, B and C) between the Wap SE and Ramp3 were generated. While loss of CTCF at site B (ΔB) had no apparent effect, loss of site A (ΔA) led to an expansion of H3K27ac from the adjacent SE in mammary tissue. The site C mutation (ΔC) resulted in a two-fold induction of Ramp3 in mammary tissue. Mice lacking all three binding sites demonstrated a marked increase in Ramp3 expression, which indicates that the CBSs block expression in an additive manner. To test the possible insulator function of these in a tissue with opposing gene expression, cerebellum was chosen as Ramp3 is actively transcribed while Wap is silent. The ΔA and ΔB mice showed no phenotype, but surprisingly ΔC mice demonstrated an 80% reduction in Ramp3 expression. Analysis of ChIP-seq and DNAse-seq demonstrated that site C coincides with a cerebellum-specific enhancer, which appears to regulate Ramp3 expression. These data demonstrate that a SE can activate two genes, albeit to different degrees. Furthermore, we demonstrate that CBSs do not serve as tight genetic boundaries encapsulating transcriptional enhancers and their associated genes, but are porous borders that allow for fine tuning of transcriptional activity. Individual CBSs have a modest ability to insulate genes, but a cluster of CTCF proteins is required to adjust the enhancer activity on genes and prevent deregulation. In addition, we show that CBSs are not restricted to a unique function and can act in a tissue-specific manner to contribute to gene regulation. These data help us to develop a more nuanced understanding of SE function as well as the roles of CTCF in regulating gene expression. Previous studies have shown that SEs and CBSs are mutational hotspots in cancer, implicating them in tumorigenesis. A more complete understanding of their biology will allow a better understanding of their role in cancer. Citation Format: Michaela Willi, Tyler M. Kuhns, Kyung Hyun Yoo, Fabian Reinisch, Christian Reinbold, Teresa Mohr, Chaochen Wang, Lothar Hennighausen. The role of super-enhancers and genetic boundaries in gene regulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4993. doi:10.1158/1538-7445.AM2017-4993

Effects of dietary CLA supplementation, parity and different concentrate levels before calving on immunoglobulin G1, G2 and M concentrations in dairy cows

Peripartal dairy cows exhibit a higher susceptibility for infectious diseases, which might be linked to the negative energy balance occurring at the onset of lactation. A dietary supplementation of conjugated linoleic acids (CLA) may reduce milk fat yield and subsequently lower the energy deficit. The utilization of immunoglobulins (Ig) for colostrogenesis might impair humoral immunity in peripartal dairy cows; therefore this study investigated the effects of a CLA supplement, parity and different dietary energy levels on plasma and colostrum IgG1, IgG2 and IgM levels in dairy cows and their calves. Blood samples were collected from 64 cows from 21days before until 56days after parturition and colostrum samples for the first 3days of lactation. Plasma immunoglobulin concentrations of 19 calves were determined before colostrum uptake. Neither plasma IgG1, nor IgG2 levels were affected by CLA or dietary energy level. However, immunoglobulin levels were affected by parity. Heifers possessed the lowest IgG1 concentrations. IgG2 concentrations were highest in cows with 2 lactations prior to parturition and in heifers after parturition. Plasma IgM levels were characterized by a sharp decrease 3days prior to parturition and were scarcely affected by the feeding regimen or parity. Generally, immunoglobulin levels appear to be mostly independent from the peripartal energy balance of the cows and are not influenced by dietary CLA. However, pronounced differences among parities for IgG1 and IgG2 were revealed which should be further evaluated.

Identification of Interleukin 40, a novel B cell-associated cytokine.

Abstract We have identified a novel mouse and human cytokine. IL-40 is normally produced in the bone marrow and fetal liver, and by activated B cells. Its sequence predicts a small (~27kDa) secreted protein unrelated to other cytokine gene families, that we have called Interleukin 40 (IL-40). IL40 is only present in mammalian genomes, suggesting a role in mammalian immune responses. Accordingly, IL-40 expression is induced in the mammary gland upon the onset of lactation, and an IL-40−/− mouse exhibits reduced levels of IgA in the serum, gut, feces, and milk. Furthermore, the IL-40−/− mouse has smaller and fewer Peyer’s patches and IgA secreting cells. The gut microbiome of IL-40−/− mice also exhibits altered composition, reflecting the reduced levels of IgA in the gut. We have also determined that B cell precursor populations are altered in the IL-40−/− mouse. Taken together, these observations indicate that IL-40 represents a novel B cell associated cytokine, that plays an important role in the development of humoral immune responses. IL-40 is also expressed by human activated B cells and by several human B cell lymphomas. The latter observation suggests that it may play a role in the pathogenesis of these diseases.

Lactation Advice Through Texting Can Help (LATCH): An Analysis of Intensity of Engagement via Two‐Way Text Messaging

Rates of breastfeeding initiation and duration among women who attend the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) are dramatically lower than non‐participants. Innovative solutions are needed to improve breastfeeding rates in this population. The LATCH study was one such approach, designed to augment and reinforce the WIC breastfeeding peer counseling process. The purpose of this study was to examine intensity of engagement via two‐way text messaging in a sample of women attending the WIC breastfeeding peer counseling program and enrolled in LATCH. The objectives were to: (1) Describe intensity of text message engagement in the context of LATCH; and (2) Assess the association between intensity of engagement and exclusive breastfeeding status. Text messaging data were first coded qualitatively by two independent researchers and intensity of engagement variables created. An analysis of intensity of engagement was conducted using descriptive statistics for normally distributed data and binary logistic regression.Participants (N = 70) were on average 26.8 years old (SD = 5.0; range: 18 – 41) with an average pre‐pregnancy weight of 158.1 pounds (SD = 46.8) and average body mass index of 28.0 (SD = 6.7), which falls in the overweight range. The average gestational age at recruitment was 23.4 weeks (SD = 3.2; range: 14 – 28). Nearly three‐quarters of the sample self‐identified as Hispanic, more than two‐thirds were single‐never married, more than three‐quarters were living with their partner, 65.7% had other children at home, 61.2% spoke English primarily, and 40.0% had more than a high school education. More than half of participants (55.2%) had previous breastfeeding experience and of those who had other children at home (n=46), just 8 had no previous breastfeeding experience.A larger volume of one‐ and two‐way SMS exchanges and MMS clicks occurred during the prenatal period. However, only post partum intensity of engagement was significantly associated with breastfeeding status at two weeks such that those who were exclusively breastfeeding averaged 1.26 more two‐way exchanges compared to the partial/no breastfeeding women (p = 0.037). The average number of breastfeeding issues addressed by BFPC's in the post partum period was significantly associated with breastfeeding status. Those who were exclusively breastfeeding had an average of 1.31 more breastfeeding issues addressed than partial/no breastfeeding women (p =0.008). In the multivariable model, controlling for baby's age at the time of the two week interview, onset of lactation, mother's age, parity, pre‐pregnancy BMI, and infant feeding intentions, the number of breastfeeding issues addressed during the first two weeks post partum was the single strongest predictor of exclusive breastfeeding status [OR = 1.69; 95% CI (1.12, 2.57)]. Pre pregnancy BMI also significantly predicted exclusive breastfeeding status [OR: 0.88; 95% CI (0.79, 0.98)]. LATCH is an innovative intervention designed to enhance the capacity of breastfeeding peer counselors and holds much potential for improving exclusive breastfeeding rates in this population.Support or Funding InformationThis project has been funded with Federal funds from the U.S. Department of Agriculture, Food and Nutrition Service through grant WIC NEI‐12‐TX to Baylor College of Medicine to Dr. Rafael Pérez‐Escamilla at Yale University. The contents of this publication do not necessarily reflect the view or policies of the U.S. Department of Agriculture, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

The Effect of Prepartum Adiposity and Lipolysis on Gestational and Postnatal Oxylipids Biosynthesis

Gestational diabetes is associated with increased lipolysis and adipose tissue (AT) inflammation, which impair insulin signaling during the second half of pregnancy and in early lactation. Prevalence of gestational diabetes is high in overweight and obese women; similarly, dairy cows with high adiposity exhibit a surge in AT lipolysis and inflammatory responses during the last trimester of gestation that lead to AT insulin resistance. Oxidized FA (oxylipids) can modulate inflammatory responses during lipolysis. Linoleic acid (LNA) and arachidonic acid (AA) derived oxylipids, including hydroxy‐octadecadienoic acids (HODE), oxo‐octadecadienoic acids (oxoODE), and hydroxy‐eicosatetraenoic acids (HETE), were recently identified as potential biomarkers for early detection of insulin resistance. However, the effects of adiposity and lipolysis rate during late gestation and early lactation on oxylipid biosynthesis including FA substrate availability is currently unknown. We hypothesized that periparturient profiles of serum and AT concentrations of PUFA and oxylipids are dependent on body adiposity and lipolytic rate. Blood and subcutaneous AT samples were collected from multiparous Holstein cows with high (HA; n=5) or low (LA; n=4) adiposity scores at −27±7 (FO) and −10±5 (CU) d prepartum and at 8±3 d postpartum (PP). Targeted lipidomic analysis was performed on plasma and AT using HPLC‐MS/MS. We report that circulating free FA (FFA) concentrations increased as parturition approached, and peaked at PP. Across time, HA increased the concentration of circulating FFA compared to LA, reflecting a significant effect of adiposity on lipolytic rate during the periparturient period. Serum concentrations of AA and eicosapentanoic acid (EPA) were decreased at CU, compared to the other timepoints for all cows. Across time, serum AA and docosahexanoic acid (DHA) concentrations were decreased in HA compared to LA. AT content of AA and DHA, as well as LNA content in AT and serum, were unchanged throughout the study and were not influenced by adiposity. There were effects of both adiposity and timepoint on oxylipid concentrations. In AT, 13‐HODE, 5‐HETE, and 11‐HETE were increased at PP compared to FO and CU. Compared to LA, HA had decreased AT concentrations of 9‐HODE,13‐HODE, 5‐HETE, and 15‐HETE. Serum concentration of 9‐oxoODE was increased at PP and was positively correlated with serum FFA concentration (r=0.52. P=0.01), but was unaffected by adiposity. These data demonstrate that prepartum adiposity may limit the availability of serum PUFA, such as DHA, which serve as substrates for anti‐inflammatory oxylipids. Furthermore, lipolysis during late gestation and the onset of lactation may enhance AT biosynthesis and systemic release of HODE and HETE into circulation.Support or Funding InformationUSDA‐NIFA grants 2014‐68004‐21972 and 2015‐67015‐23207Michigan Alliance for Animal Agriculture Effect of adiposity and sampling time point across late gestation and early lactation on fatty add composition and oxylipid profile of subcutaneous adipose tissue and serum (mean + SEM) of dairy cows. Adiposity Sampling Metabolite Low (LA) High (HA) SEM P Far off (FO) Close‐up (CU) Postpartum (PP) SEM P Serum free fatty acids (FFA) mEq/L FFA 0.43 0.63 0.05 <0.01 0.27a 0.34b 0.98c 0.06 <0.01 Serum fatty acids μmol/L Linoleic 341.5 222.6 78.8 NS 205.2 187 454 81.8 NS Arachidonic 42.2 20 10.5 0.02 22.2a 17.4a 53.8b 16.1 0.01 EPA 2.5 0.9 0.8 NS 0.7a 0.5a 2.7b 0.4 0.01 DHA 0.8 0.4 0.1 0.03 0.7 0.4 0.7 0.2 NS Adipose tissue fatty acids μmol/mg Linoleic acid 1340 1110 360 NS 1570 420 1720 500 NS Arachidonic acid 43.5 46.2 17 NS 43.9 9.3 52.4 16 NS EPA 0.83 0.43 0.3 NS 0.9 0.14 1.12 0.4 NS DHA 0.17 0.24 0.1 NS 0.23 0.31 0.07 0.2 NS Adipose tissue oxylipids nM/mg 9‐HODE 1.52 0.63 0.63 0.01 0.59 0.67 1.9 0.5 NS 9‐oxoODE 0.97 0.62 0.35 NS 0.49 1.01 0.87 0.26 NS 13‐HODE 2.42 0.71 0.84 0.05 0.77a 0.95a 2.97b 0.7 0.05 13‐oxoODE 0.62 0.62 0.47 NS 0.32 0.5 1.09 0.38 NS 5‐HETE 0.6 0.33 0.12 0.05 0.24a 0.56b 0.6b 0.12 0.05 11‐HETE 0.16 0.09 0.04 0.03 0.1a 0.08a 0.2b 0.04 0.04 15‐HETE 0.29 0.04 0.08 0.01 0.06a 0.12b 0.42c 0.08 0.01 20‐HETE 0.007 0.007 0.01 NS 0.007 0.007 0.006 0.004 NS Serum oxylipids nM/mL 9‐HODE 140.47 141.5 68.44 NS 210.98 111.45 101.65 60.4 NS 9‐oxoODE 82.3 67.6 36.76 NS 79.64a 87.41a 131b 41.3 0.02 13‐HODE 302 309.67 119.44 NS 364.14 301.73 252.77 98.5 NS 13‐oxoODE 31.97 19.18 2.09 NS 36.47 10.58 23.45 15.66 NS 5‐HETE 13.38 20.59 11.04 NS 12.62 29.75 5.55 10.58 NS 11‐HETE 8.65 7.98 4.69 NS 7.48 9.02 8.43 4.09 NS 15‐HETE 10.31 8.64 5.36 NS 10.72 11.8 5.82 4.87 NS 20‐HETE 26.45 28.45 1.7 NS 5.16 32.55 6.65 16.44 NS EPA=eicosapentaenoic acid; DHA=docosahexaenoic acid; HODE=hydroxyoctadecadienoic acid; oxoODE=oxooctadecadienoic acid; HETE= hydroxyeicosatetraenoic acid. Means in same row with different letter differ between sampling timepoint, P < 0.05. NS= non‐significant effect, P > 0.05.

Effect of increasing body condition on oxidative stress and mitochondrial biogenesis in subcutaneous adipose tissue depot of nonlactating dairy cows

With the onset of lactation, dairy cows with a body condition score >3.5 are sensitive to oxidative stress and metabolic disorders. Adipose tissue (AT) can adapt to varying metabolic demands and energy requirements by the plasticity of its size during lactation. In AT, angiogenesis is necessary to guarantee sufficient oxygen and nutrient supply for adipocytes. Cellular energy metabolism is reflected mainly by mitochondria, which can be quantified by the mitochondrial DNA copy number per cell. In the present study, we aimed to investigate the effect of overconditioning on angiogenesis and mitochondrial biogenesis in AT of nonlactating cows, irrespective of the physiological influences of lactation and pregnancy. Eight nonpregnant, nonlactating cows received a ration of increasing energy density for 15 wk, during which body weight and body condition increased substantially. Subcutaneous AT was biopsied every 8 wk, and blood was sampled monthly. The blood concentrations of indicators of oxidative stress increased continuously throughout the experimental period, possibly damaging mitochondrial DNA. Concomitantly, HIF-1α, a major marker for hypoxia, increased until wk 8, indicating insufficient angiogenesis in the rapidly expanding AT. Based on the observation that the number of apoptotic cells decreased with increasing hypoxia, the increasing mitochondrial DNA copy numbers might compensate for the hypoxia, reinforcing the production of oxidative stressors. Key transcription factors of mitochondrial biogenesis were largely unaffected. Thus, increased oxidative stress does not impair mitochondrial DNA.

Effects of a sustained release formulation of 1,25-dihydroxyvitamin D3-glycosides for milk fever prevention on serum 1,25-dihydroxyvitamin D3, calcium and phosphorus in dairy cows

Milk fever (MF) is a metabolic disease in dairy cows around parturition. The clinical lead sign is muscular paresis leading in severe cases to paralysis of the affected animal. Multiparturient animals of high performing dairy breeds are most likely to be affected and have a high probability of recurrence. An acute drop in blood calcium levels causes the disease when the demand for calcium at the onset of lactation exceeds the ability to replete blood calcium levels through mobilization from bone and intestinal uptake. With the understanding of the underlying mechanism, calcium supply management and vitamin D supplementation became prime candidates for MF prevention and therapy. Several strategies have been developed for MF prevention. Application of the active form of Vitamin D, 1,25(OH)2D3, was found to prevent MF effectively. In order to prevent a delayed hypocalcemia, which was occasionally seen after stopping the treatment with 1,25(OH)2D3, a new approach was chosen by applying Solanum glaucophyllum extract (SGE), which contains 1,25(OH)2D3-glycosides, as instant-release (irSGE) in combination with slow-release (srSGE) tablets.In a first study, non-lactating cows were treated with a single bolus of either synthetic 1,25(OH)2D3, irSGE, or srSGE and the results were compared to a control group without treatment. Blood serum levels of 1,25(OH)2D3 (1,25D), calcium (Ca), phosphate (P) and magnesium (Mg) were followed for 11days and the area under the curve (AUC) was calculated. Calcium and phosphate excretion in urine were determined during 15days. While serum concentration of 1,25(OH)2D3 was back to pre-treatment level in the irSGE, srSGE and 1,25(OH)2D3 treated group within 3days, calcium and phosphate levels remained elevated for up to 9days. AUC of serum 1,25(OH)2D3 was 2.89 (1,25D), 3.13 (irSGE) and 4.21 (srSGE) times higher than control. Serum calcium levels were 1.07* (for 1.25D); 1.08* (for irSGE) and 1.12* (for srSGE) times higher than control. Serum phosphate levels were 1.20* (for 1,25D); 1.30* (for irSGE) and 1.41* (for srSGE) times higher than control, with * p<0.05. In a second field study calving cows treated with one bolus containing ir- and sr- tablets of SGE were compared to an untreated control group and to a group treated with 4 boli of commercial calcium salts. As a result, calcium serum levels increased (+19% compared to baseline) around calving after treatment with the single bolus of SGE. The single bolus of SGE lead also to an increase of serum phosphate (+31% compared to baseline). These calcium and phosphate increases were statistically significant (p<0.001) 0–24h after calving compared to the control group and to the group treated with calcium salts. The sample size of the study was too small to draw a conclusion on the effect on MF prevention.In conclusion, application of a single bolus of a SGE extract lead to an increase of serum calcium and phosphate for up to 9days and may thus have the potential to prevent a hypocalcemia and −phosphatemia, an important cause for clinical milk fever.

The effect of nefopam on lactation after caesarean section: a single-blind randomised trial

BackgroundNefopam is a centrally acting analgesic which has a theoretical risk of stopping lactation due to its anticholinergic and dopaminergic effects. The aim of this study was to evaluate the effect of nefopam on lactation and to investigate potential adverse effects on newborns. MethodsSeventy-two women, scheduled to undergo a caesarean delivery under spinal anaesthesia and wanting to breastfeed, were randomised to one of two groups: nefopam (20mg, six hourly) or paracetamol (1g, six hourly). In both groups, postoperative analgesia was supplemented with ketoprofen (50mg, six hourly) in conjunction with intrathecal morphine 0.1mg. The primary outcome was onset of lactation, estimated by weighing the newborns before and after feeding; by maternal perception of breast fullness and based on serum prolactin concentration 48hours postpartum. Secondary outcomes were neonatal adverse effects evaluated by neurobehavioural score at 12, 24, 48, and 72hours after birth. Statistical analyses were performed using Chi-squared, Fisher exact and Student t tests as appropriate. P<0.05 was considered statistically significant. ResultsThe difference in the weight of the newborn before and after each feed, maternal perception of breast fullness and serum prolactin did not significantly differ between groups. The volume of artificial milk given to newborns of mothers in the nefopam group on days two and three was significantly greater than for the paracetamol group. Neurobehavioural scores were comparable at each time point. ConclusionNefopam does not appear to delay the onset of lactation or present any clear risk to the newborn.

Crucial genes at the onset of lactation revealed by transcriptome screening of Domestic Yak mammary gland

At the onset of lactation, there are three distinct stages of mammary tissue development and function including mammogenesis, colostrogenesis, and lactogenesis. The mechanism of the transition from colostrogenesis to lactogenesis of Maiwa Yak is still unknown. In this study, mammary tissues from three Maiwa Yaks were collected at 1 and 30 d after parturition for transcriptome exploration using Affymetrix Bovine Genome Arrays. Comparing 1 and 30 d results, a total of 517 annotated differentially expressed genes (DEGs) were identified at the criteria of a P ≤ 0.05. The ratio of up-regulated genes to the down-regulated ones was around 1:2 (more specifically, 164:353). To depict the profile of DEGs, a dynamic impact approach (DIA) was used to analyse the microarray data based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. GO terms “fatty acid transport” and “monocarboxylic acid transport” were significantly induced during the colostrum period. The strongly impacted KEGG pa...

Effects of precalving body condition and prepartum feeding level on gene expression in circulating neutrophils

Extensive metabolic, physiological, and immunological changes are associated with calving and the onset of lactation. As a result, cows transitioning between pregnancy and lactation are at a greater risk of metabolic and infectious diseases. The ability of neutrophils to mount an effective immune response to an infection is critical for its resolution, and increasing evidence indicates that precalving nutrition affects postpartum neutrophil function. The objectives of the current study were to investigate the effect of 2 precalving body condition scores (BCS; 4 vs. 5 on a 10-point scale) and 2 levels of feeding (75 vs. 125% of estimated maintenance requirements) on gene expression in circulating neutrophils. We isolated RNA from the neutrophils of cows (n = 45) at 5 time points over the transition period: precalving (-1 wk), day of calving (d 0), and postcalving at wk 1, 2, and 4. Quantitative reverse transcriptase PCR with custom-designed primer pairs and Roche Universal Probe Library (Roche, Basel, Switzerland) chemistry, combined with microfluidics integrated fluidic circuit chips (96.96 dynamic array), were used to quantify the expression of 78 genes involved in neutrophil function and 18 endogenous control genes. Statistical significance between time points was determined using repeated measures ANOVA with Tukey-Kramer multiple-testing correction to determine treatment effects among weeks. Precalving BCS altered the inflammatory state of neutrophils, with significant increases in overall gene expression of antimicrobial peptides (BNBD4 and DEFB10) and the anti-inflammatory cytokine IL10, and significantly decreased expression of proinflammatory cytokine IL23A in thinner cows (BCS 4) compared with cows calving at BCS 5. Feeding level had a time-dependent effect on gene expression; for example, increased expression of genes involved in leukotriene synthesis (PLA2G4A and ALOX5AP) occurred only at 1 wk postcalving in cows overfed (125% of requirements) precalving compared with those offered 75% of maintenance requirements. Results indicate that precalving body condition and changes in prepartum energy lead to altered gene expression of circulating neutrophils, highlighting the importance of transition cow nutrition for peripartum health.

Association Between Gestational Weight Gain and Delayed Onset of Lactation: The Moderating Effects of Race/Ethnicity.

In the United States, a high percentage of pregnant women gain weight outside of the current Institute of Medicine's (IOM) gestational weight gain (GWG) recommendations. There is limited research examining the relationship between GWG and onset of lactation. Delayed onset of lactation (DOL) can negatively affect breastfeeding outcomes. Secondary data analysis was conducted using data from 2,053 women who participated in the population-based Infant Feeding Practices Study II between 2005 and 2007. The main outcome of interest was maternal perception of DOL, defined as milk coming in >3 days postpartum. Three categories of GWG were created based on the IOM's revised cutoff: inadequate, adequate, and excessive. Descriptive statistics and multivariable logistic regression modeling were performed. Interactions between GWG and race/ethnicity on DOL were examined to test whether the relationship between GWG and DOL differs by race/ethnicity. Overall, 23.7% of the study sample reported DOL. Of these, 49.5% and 19.5% of women had excessive GWG and inadequate GWG, respectively. After adjusting for potential confounders, there was a significant interaction between GWG and race/ethnicity on DOL. Among non-Hispanic white women, the odds of DOL were higher in women with excessive GWG compared to those who had the recommended GWG (OR 1.47, 95% CI 1.14-1.90, p = 0.003). For other race/ethnicity groups, no significant relationships between GWG and DOL were detected. With the increasing rates of excessive GWG, it is critical to identify populations at increased risk of DOL and provide targeted breastfeeding support, especially in the early postpartum period.

Hemato-Biochemical Profiling in Relation to Metabolic Disorders in Transition Dairy Cows

This study was aimed to provide a complete picture of dynamics of selected hematological and serum biochemical parameters in dairy cows from late pregnancy to early postpartum period, giving new and useful information about the guidelines for the management strategies during different physiological phases. This study was carried out on thirty clinically healthy Holstein Friesian dairy cows; in good nutritional condition. Blood samples were collected two weeks before the expected parturition , during the 1st post-partum week and during the 3rd week after parturition. Cows under investigation were clinically examined including body temperature, pulse, respiration, mucous membranes and ruminal movement. Two blood samples were collected: whole blood samples for hematological picture, while serum samples for biochemical analysis which included total proteins, albumin , globulin , AST, ALT, glucose, Creatinine, Blood urea nitrogen (BUN), Total cholesterol, Beta hydroxy butyrate (βHBA), triglycerides, Nitric Oxide (No), Malondialdehyde (MDA), total antioxidant capacity (TAC), serum calcium, magnesium, sodium, potassium, chloride and phosphorus. Significant changes between pre and post-partum period were observed in values of hemogram and biochemical parameters including RBCs, PCV%, hemoglobin, MCV, MCHC, MCH, WBCS count and differential leucocytic count, total proteins, albumin, globulin, glucose, BUN, Total cholesterol, triglycerides, calcium, phosphorus, magnesium, sodium, chloride, No, MDA and TAC, while non-significant changes were observed in AST, ALT, Potassium ,Creatinine and βHBA levels. It can be concluded that late pregnancy and the onset of lactation were accompanied by marked changes in hemato-biochemical and oxidative stress markers which have great impact on dairy cow`s health, immunity and disease susceptibility.

Metabolic and mineral conditions of retained placenta in highly productive dairy cows: pathogenesis, diagnostics and prevention – a review

The time around calving in highly productive dairy cows is a critical period in terms of their metabolism, which is connected with high demands of the foetus as well as with the onset of lactation. Retained placenta in cows may have multifactorial aetiology, but in herds which are free from infectious diseases, the most important reasons are; periparturient metabolic changes and disturbances to the internal balance and stress. During the periparturient period, the most important factor causing immune suppression and hypotony of uterus in cows is metabolic stress due to hormonal and nutritional factors, including metabolic fluctuations, negative energy balance, as well as shortage of proteins, minerals, vitamins and antioxidants. This metabolic stress as a result of an imbalance in the internal metabolic homeostasis activates the hypothalamic-pituitary-adrenocortical axis (HPA) and increases serum corticosterid (cortisol) concentration, especially on the day of calving. Cortisol is a powerful immune suppressive factor that causes depression of leukocyte proliferation and their functions. The periparturient metabolic stress may also stimulate the production of catecholamines, especially adrenalin. Elevated levels of adrenalin activate adrenoreceptors of the myometrium, which in turn cause hypotony or atony of the uterus at calving in cows. Elevated levels of cortisol and adrenalin may significantly inhibit the rejection and expulsion of foetal membranes in cows, resulting in an increased incidence of their retention. These important mechanisms for placental retention in highly productive dairy cows often have primary nutritional metabolic aetiology, but they also occur during secondary metabolic disturbances and metabolic stress during calving. This metabolic and immunological aetiology and pathogenesis of retained placenta usually occur in highly productive periparturient cows on dairy farms in the absence of bovine infectious diseases, which can couse placentitis, stillbirth and the infectious origin of foetal membrane retention. The paper presents the most important metabolic, mineral and immunological disturbances as conditions for retained placenta in dairy cows. It also shows different methods of herd monitoring, important examples of clinical and laboratory diagnostics, and methods of nutritional and veterinary prevention of this health problem in dairy cows.

ONSET PENGELUARAN KOLOSTRUM PADA IBU POST PARTUM DENGAN PERSALINAN NORMALVLEBIH CEPAT DARIPADAVPERSALINAN SECTIO CAESARIA

Background : Lactation onset is a term of multiplying breast milk until the release of breast milk for the first time or mothers’ perception on when her breast milk will be released which is marked by a bit hard breast, inflammed, and full of breast milk or the release of colostrum. Colostrum is the first liquid secreted by breast milk gland since the first day until the fourth day. One of factors which influences lactation onset is labor method and early breastfeeding initiation (IMD). Mothers who undergo sectio caesaria surgery will feel painful and the effect of prolonged usage of anesthesia so that early breastfeeding initiation cannot be implemented compared to mothers with normal labors and the usage of anesthesia which slows down lactation onset.&#x0D; Objective : To find out the difference between colostrum releasing onset in post partum mothers with normal labors and sectio caesaria in Panembahan Senopati General Hospital, Bantul. Method : The design of this study was cross sectional. The number of samples were 80 respondents selected with purposive sampling technique. Study instrument was observational sheets. Data analysis applied Mann-Whitney test.&#x0D; Result : The majority of respondents who had normal labors and sectio caesaria experienced different colostrum onset. In normal labors, the time of colostrum release was 1 day. In sectio caesaria labors, the time of colostrum release was 2 days. The average duration of post partum mothers with normal labors was 13,6 hours and post partum mothers with sectio caesaria was 22,6 hours. The result of Mann-Whitney test was that there was a difference between colostrum release onset of post partum mothers with normal labors and sectio caesaria with p value 0,001 (p&lt;0,05) which implied that Ho was rejected.&#x0D; Conclusion : Normal labors and sectio caesaria labors had different colostrum onset.&#x0D; &#x0D; Keyword : Colostrum, Normal labors, Sectio Caesaria labors.

Increased serum serotonin improves parturient calcium homeostasis in dairy cows

Hypocalcemia in dairy cows is caused by the sudden increase in calcium demand by the mammary gland for milk production at the onset of lactation. Serotonin (5-HT) is a key factor for calcium homeostasis, modulating calcium concentration in blood. Therefore, it is hypothesized that administration of 5-hydroxy-l-tryptophan (5-HTP), a 5-HT precursor, can increase 5-HT concentrations in blood and, in turn, induce an increase in blood calcium concentration. In this study, 20 Holstein dairy cows were randomly assigned to 2 experimental groups. Both groups received a daily i.v. infusion of 1 L of either 0.9% NaCl (C group; n = 10) or 0.9% NaCl containing 1 mg of 5-HTP/kg of BW (5-HTP group, n = 10). Infusions started d 10 before the estimated parturition and ceased the day of parturition, resulting in at least 4 d of infusion (8.37 ± 0.74 d of infusion). Until parturition, blood samples were collected every morning before the infusions, after parturition samples were taken daily until d 7, and a final sample was collected on d 30. Milk yield was recorded during this period. No differences between groups were observed for blood glucose, magnesium, and β-hydroxybutyrate. Cows receiving the 5-HTP infusion showed an increase in fatty acid concentrations from d -3 to -1 before parturition. Serum 5-HT concentrations were increased at d -4 related to parturition until d 5 postpartum in the 5-HTP group compared with the C group. In addition, cows from the 5-HTP group had increased 5-HT concentrations in colostrum, but not in mature milk, on d 7 postpartum. Serum calcium concentrations decreased in both groups around parturition; however, calcium remained higher in the 5-HTP group than in controls, with a significant difference between groups on d 1 (1.62 ± 0.08 vs. 1.93 ± 0.09 mmol/L in control and 5-HTP groups, respectively) and d 2 (1.83 ± 0.06 vs. 2.07 ± 0.07 mmol/L in control and 5-HTP groups, respectively). Additionally, colostrum yield (first milking) was lower in the 5-HTP group compared with the C group, but without consequences on colostrum IgG concentrations. Milk yield did not differ between groups during the rest of the experiment. The study data were consistent with the concept that infusion of 5-HTP to dairy cows increases blood 5-HT concentrations, which in turn is a significant regulatory component in the chain of effectors that affect calcium status around parturition, hence the occurrence of clinical or subclinical hypocalcemia.

Prevalence of and risk factors for delayed onset of lactation in Chinese lactating women in 2013

Objective: To study the prevalence of delayed onset of lactation (later than 3 days) in lactating women in China and to analyze its influencing factors. Methods: Data were extracted from Chinese National Nutrition and Health Surveillance-Mothers, from mothers with children under 2 years of age (in 2013). A total of 11 178 women who were lactating or had lactated were selected from 55 counties of 30 provinces (excluding the Tibet Autonomous Region) in China, using the multi-stage stratified cluster randomization sampling method. Basic information, including onset of lactation, initiation of breastfeeding, breastfeeding difficulties and breastfeeding knowledge were collected using a questionnaire investigation. The prevalence of delayed onset of lactation were analyzed by the weighted processing of complex sampling from the 6th national population census data. A multiple logistic regression was used to analyze the factors associated with delaged onset of lactation. Results: Among 11 178 lactating women, 3 388 had an onset of lactation later than 3 d. The prevalence of delayed onset of lactation was 30.3%. After complex weighting, the prevalence of delayed onset of lactation was 31.2% (95% CI: 25.7%-36.8%) for lactating women in China. Delivery by Caesarean section (OR=1.28, 95%CI: 1.06-1.53) and initiating breastfeeding ≥4 h (OR= 2.34, 95%CI: 1.76-3.11) were the negative factors for delayed onset of lactation. Compared with those living in large cities, lactating women living in medium or small cities (OR=1.39, 95%CI: 1.05-1.84) had a higher risk of delayed onset of lactation. Compared with the lactating women doing housework, the risk of delayed onset of lactation was lower (P<0.05) among those whose occupations were as leaders of Enterprises/Institutions (OR=0.68, 95%CI: 0.47-0.99), in catering and service trades (OR=0.61, 95%CI: 0.43-0.86), in agriculture/forestry/fishery/herdsmen fields (OR=0.65, 95%CI: 0.44-0.96) and who were unemployed (OR= 0.64, 95%CI: 0.46-0.90). Breastfeeding education during pregnancy might lower the risk of delayed onset of lactation (OR=0.78, 95% CI: 0.62-0.98). Conclusion: The prevalence of delayed onset of lactation was relatively high for Chinese lactating mothers. Caesarean section and late initiation of breastfeeding were the primary risk factors. Lactating mothers living in medium or small cities and those doing housework appear to be high-priority groups for intervention. Based on our findings, breastfeeding education during pregnancy is recommended to lower the risk of delayed onset of lactation.

Parity differences in the behavior of transition dairy cows

During the transition period, around the time of calving, cows experience a suite of stressful events, including regrouping, diet changes, parturition, and the onset of lactation. These changes may be more difficult for primiparous cows that have not had these experiences previously. The objective of this study was to compare feeding, social, exploratory, and lying behaviors of primiparous and multiparous cows during the transition period. Thirty-eight healthy primiparous and 62 healthy multiparous dairy cows were housed in mixed-parity groups of 20 with access to 12 electronic feed bins from 3wk before to 3wk after calving. Primiparous cows had lower dry matter intake, spent more time feeding, ate more slowly, visited the feeder more frequently, and explored their feeding environment more compared with multiparous cows. Primiparous cows also lay down more frequently, but for shorter periods, such that total lying time did not differ between these parity classes. Primiparous cows were also replaced at the feeder more often than multiparous cows. These results show how the behavior of primiparous and multiparous cows differs during the transition period, and support the idea that primiparous cows may benefit from different management during this period.