Energy dynamics during the perinatal period. Jeremy Miles U.S. Meat Animal Research Center NSIF Annual Meeting December 4, 2014

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1 Energy dynamics during the perinatal period Jeremy Miles U.S. Meat Animal Research Center NSIF Annual Meeting December 4, 204

2 Objective for today s talk Sow lifetime productivity & associated factors Preweaning mortality at U.S. MARC Energy metabolism during the perinatal period Utility of the Chinese Meishan pig as a model for improved preweaning survival

3 Sow lifetime productivity (SLP) Number of pigs weaned in a sow s lifetime Possible goal of 65 pigs weaned per lifetime (Gill 2007) Current U.S. sow productivity ~40 (Stalder et. al 2009) Must maintain extra sows to reach optimal production rates Conservative increase of 5 weaned piglets to match the top 25% U.S. benchmark of 45 weaned pigs would equate to increased revenue of ~$ billion

4 Factors associated SLP Gilt development Age of puberty Age at first service Pigs weaned per litter (~0.5) Litter size (NBA~.8) Stillbirth rate (~6.9%) Preweaning mortality rate (~4.0%) Litters in a sow s lifetime (~4.5) Gestation length (~5.3 d) Lactation period (~8.2 d) Return to estrus after weaning interval (~7.9 d) Culling rate (~53%) Numbers from PIGCHAMP 200

5 Early life is very difficult for piglets Please imagine, gentle reader, that you suddenly find yourself beside a recumbent elephant in small, locked room. The elephant seems agitated; she periodically jumps to her feet and then crashes to the floor, and may even whirl about and attack you without warning. Unfortunately, you entered the room by being squeezed through a narrow tube and perhaps partly suffocated, so that you are none too steady on your feet. You ought to keep far from the elephant as the limited space permits, but you cannot afford this luxury because you are cold, wet, unclothed, and desperately short of food; and the only source of food is the elephant s milk. Competing for this resource, however, are 0 or more individuals like yourself, some of them twice your body weight, and murderously aggressive and armed with sharp teeth. Introduction statement in Behavioural perspectives on piglet survival by D. Fraser 990.

6 Predisposing factors associated with preweaning piglet mortality Low birth weight & within-litter birth weight variability (Damgaard et al. 2003) ~70-80% of preweaning mortality occurs within the first 3 days after farrowing (Tuchscherer et al. 2000) ~70-80% of preweaning mortality result from crushing by the sow (Marchant et al. 2000) Most of the mortality from crushing is actually secondary to malnutrition and underdevelopment (Fraser 987)

7 Preweaning mortality at U.S. MARC

8 Litter statistics U.S. MARC (20-204) Composite Landrace-Duroc-Yorkshire (200; BX) bred with either Landrace or Yorkshire commercial semen Data set from 3,086 mixed parity litters (average 2.83) Litter averages: TNB =.7; TBA = 0.7; pigs weaned = 8.9 Variable Number Percentage Total number born (TNB) 36,9 - Mummies a % Stillborn a 2,9 5.8% Total born alive (TBA) 33,07 - Total preweaning mortality b 5, % First three day mortality c 4, % a Percentage of total number born b Percentage of total born alive c Percentage of total preweaning mortality

9 Breakdown of preweaning mortality (PWM) causes at the U.S. MARC First 72 h PWM (% within group) Total PWM (% within group) Total observations Trauma (overlay, crush, stepped on) 2976 (73.8) 3794 (65.7) Nutritional (runt, starvation, weak) 64 (5.2) 969 (6.8) Euthanized (deformity, crippled) 29 (5.4) 298 (5.2) Kill by other (primarily sow) 5 (3.7) 52 (2.6) Immunological (sick, infection, scours) 43 (.) 44 (7.2) Unknown cause 34 (0.8) 85 (.5) Castration issue N.A. 60 (.0)

10 Percentage Birth weight distribution for the entire population and trauma mortality early (PWM 72h) and throughout lactation (PWM All) Population; average =.58 PWM 72 h; average =.32 PWM All; average =.36 Mixed model analysis illustrates a significant (P < 0.00) effect of BW for those surviving compared to those lost by trauma (.62 ± 0.0 to.33 ± 0.0) Birth weight (kg)

11 Size matters! Smaller offspring = greater probability of mortality Developmental issue with problems occurring during prenatal development Uterine crowding influenced by litter size (van der Lende et al. 200) and maternal malnutrition (Foxcroft et al. 2006) Abnormal development of cardiovascular and hematological systems (Orgeig et al. 200) Deficiencies in perinatal energy stores and blood components relating to energy (Stone et al. 985; Randall 992; Herpin et al. 993; Miles et al. 202)

12 Adaptations to extrauterine life Breathing and circulation Clearance of fetal lung fluid, increased surfactant secretion, and initiation breathing (Hillman et al. 202) Fetal to neonatal circulation, decreased pulmonary vascular resistance, increased pulmonary blood flow & cardiac output (Sharma et al. 200) Fetal to adult hemoglobin to account for differences in oxygen tension (Rudolph 983) Thermogenesis Humans (Asakura 2004) and ruminants (Smith et al. 2004) primarily utilize nonshivering thermogenesis via metabolism of brown adipose tissue (BAT) Pigs are poorly insulated, completely lack brown adipose tissue and therefore rely almost exclusively shivering mechanisms to regulate temperature (Berthon et al. 994) Energy metabolism Maintenance of glucose homeostasis prior to establishment of enteral feeding (Mota-Rojas et al. 20) Primary driven by mobilization of energy stores via gluconeogenesis, lipolysis, and glycogenolysis (Sharma et al. 200)

13 Energy metabolism during the perinatal period

14 Glucose homeostasis of the neonate ) Neonatal energy reserves 2) Colostrum/Milk energy from the sow From Gustafsson 2009

15 Neonatal energy reserves Primary reserves Utilization of reserves Body lipids Tissue glycogen From Mellor and Cockburn 986

16 Prenatal and neonatal glycogen levels in the pig Prenatal Neonatal From Elliot & Lodge 977 From Randall & L Ecuyer 976

17 Glycogen metabolism (GSY&2) (UGP2) (AGL) (PYGM&L) (AGL) Glycogen synthesis enzymes: UGP2 UDP-glucose pyrophosporylase 2 GSY&2 Glycogen synthase &2 Glycogen degradation enyzmes: PYGM&L Glycogen phosphorylase AGL - Amylo-alpha-,6-glucosidase

18 Regulation of glycogen metabolism Glycogenesis Glycogenolysis

19 Perinatal glycogen metabolism Fetal glycogenesis Neonatal glycogenolysis - Glucose - Lactate - Fructose? - Glucose transport via GLUTs - Produce lactate & fructose - Regulatory - Responses to glucose - Controls GSY activation - Regulatory - Mediates insulin activity - Glycogen accretion - Liver & muscle - GLUT2 - Glycogenic enzymes From Fowden & Forhead 2009 From Mayor & Cueza 985

20 Milk energy from the sow Primary milk energy constituents Fat (60%) Protein (22%) Lactose (8%) From Bergsma et al Total energy (MJ/kg) Dry matter (%) Fat (%) Protein (%) Lactose (%) Milk yield (kg) Colostrum (2 h PP) Milk (d8 PP) Composition data from Le Dividich et al Milk yield from Devillers et al & van den Brand et al. 2000

21 Utility of the Chinese Meishan pig as a model for improved preweaning survival

22 Chinese Meishan pigs Farrow 3 to 5 more piglets & have improved preweaning survival compared with contemporary Western breeds (Legault 985; Lee & Haley 995) Hypotheses for improved reproductive prolificacy: Greater uniformity of conceptus development (Bazer et al. 988; Finch et al. 2002) Increased uterine capacity (Christenson et al. 993; Ford et al. 2002) Greater fetal and neonatal maturity (Le Dividich et al. 99; Herpin et al. 993) Better mothering ability (van der Steen & De Groot 992) Superior milk composition (Le Dividich et al. 99; Alston-Mills et al. 2000)

23 Contributions of maternal uterine environment and piglet genotype and their interactions on weaning survivability potential: I. Development of neonatal piglets after reciprocal embryo transfer between Meishan and White crossbreed gilts Miles JR, Vallet JL, Ford JJ, Freking BA, Cushman RA, Oliver WT and Rempel LA J Anim Sci 90:

24 Feed intake at day Maternal Environment x Piglet Genotype MS x MS MS x WC WC x MS WC x WC Pr > F a Body weight (kg) M* & P** Eviscerated BW (g) M** & P** Total wt visceral (g) P** Empty wt visceral (g) N.S. GI tract content wt (g) P** Empty GI tract wt (g) P*** a M = maternal effect, P = piglet effect, I = M*P interaction. *P < 0.0, **P < 0.05, ***P < 0.0, N.S. = non-significant.

25 Blood components at day Maternal Environment x Piglet Genotype MS x MS MS x WC WC x MS WC x WC Pr > F a Hematocrit (%) I* Hemoglobin (g/dl) I* PUN I*** Albumin (mg/ml) P** a M = maternal effect, P = piglet effect, I = M*P interaction. *P < 0.0, **P < 0.05, ***P < 0.0, N.S. = non-significant.

26 Energy stores at day Maternal Environment x Piglet Genotype MS x MS MS x WC WC x MS WC x WC Pr > F a Liver glycogen (mg/g) b N.S. Liver glycogen (mg/g) P* BF glycogen (mg/g) b N.S. BF glycogen (mg/g) P* LD glycogen (mg/g) b N.S. LD glycogen (mg/g) P* Fat (%) P* Protein (%) P* Gross energy (kcal/g) P** b Reference glycogen taken at birth from naturally breed MS and WC gilts BF Bicep femoris LD Longissimus dorsi a M = maternal effect, P = piglet effect, I = M*P interaction. *P < 0.0, **P < 0.05, ***P < 0.0, N.S. = non-significant.

27 Summary: Neonatal development Birth weight (M & P effect; WC > MS) Hematocrit, hemoglobin, & serum PUN (M*P effect; WC x MS = MS x MS > MS x WC > WC x WC) Serum albumin (P effect; MS > WC) GI tract & GI content weight (P effect; MS > WC) Liver, B. femoris, & L. dorsi glycogen (P effect; WC > MS) Fat, crude protein, & gross energy (P effect; MS > WC) Meishan piglets can serve as a useful model for preweaning survivability in regards to increased energy reserves, utilization of glycogen, activity and milk intake in the early neonate.

28 Assessment of genotypic differences in glycogen metabolism during prenatal development

29 grams Fetal body weight for Meishan (MS) & White Crossbred (WC) pigs 600 B*D; P < 0.0 MS WC Day of gestation Mixed model: Fixed effects of breed (B), day (D), interaction of fixed effects (B*D), covariate of littersize, and the random effect of gilt within B*D interaction. 6 litters and 22 fetuses.

30 mg/g Glycogen levels in MS & WC fetal livers 80 B*D; P = 0.05 MS WC Day of gestation Mixed model: Fixed effects of breed (B), day (D), interaction of fixed effects (B*D), covariate of littersize, and the random effect of gilt within B*D interaction. 36 litters and 72 fetuses.

31 RQ RQ RQ RQ Expression of glycogenic enzymes Glycogenesis enzymes Glycogenolysis enzymes 80 D; P < 0.0 UGP2 mrna MS WC 00 D; P < 0.0 PYGL mrna MS WC Day of gestation Day of gestation 80 D; P < 0.0 GYS2 mrna MS WC N.S. AGL mrna MS WC Day of gestation Day of gestation Mixed model: Fixed effects of breed (B), day (D), interaction of fixed effects (B*D), covariate of littersize, and the random effect of gilt within B*D interaction. 6 litters and 22 fetuses. N.S. = non-significant.

32 mm mm mg/ml mm mm Serum nutrients Maternal nutrients 6 N.S. Glucose MS WC 8 B*D; P = 0.05 Lactate MS WC Day of gestation Day of gestation GLM Model: Fixed effects of breed (B), day (D), interaction of fixed effects (B*D), and covariate of littersize. 6 gilts. N.S. = non-significant. Fetal nutrients 2 2 B*D; P = 0.0 Glucose MS WC 5 2 D; P < 0.00 Lactate MS WC 2 2 B; P < 0.00 D; P < 0.0 Fructose MS WC Day of gestation Day of gestation Day of gestation 2 Mixed model: Fixed effects of breed (B), day (D), interaction of fixed effects (B*D), covariate of littersize, and the random effect of gilt within B*D interaction. 6 litters and 22 fetuses.

33 µu/ml pg/ml ng/ml µu/ml pg/ml ng/ml Serum regulatory components Maternal regulatory components 24 8 B; P = 0.05 Insulin MS WC N.S. Glucagon MS WC N.S. Cortisol MS WC Day of gestation Day of gestation Day of gestation GLM Model: Fixed effects of breed (B), day (D), interaction of fixed effects (B*D), and covariate of littersize. 6 gilts. N.S. = non-significant. Fetal regulatory components 6 B*D; P < 0.05 Insulin MS WC B*D; P < 0.0 Glucagon MS WC 60 D; P < 0.00 Cortisol MS WC Day of Gestation Day of gestation Day of gestation Mixed model: Fixed effects of breed (B), day (D), interaction of fixed effects (B*D), covariate of littersize, and the random effect of gilt within B*D interaction. 6 litters and 22 fetuses.

34 Summary prenatal development Fetal body weight (WC > MS at d90 and d0) Fetal liver glycogen (MS > WC at d0) No genotypic effects on expression of glycogenic enzymes Fetal glucose (MS > WC at d0) Fetal fructose (MS > WC, irrespective of day) Fetal insulin & glucagon (MS > WC, at d0) Maternal insulin (MS > WC, irrespective of day) Meishan piglets have increased production of liver glycogen at late gestation that is driven by increased availability of glucose and insulin within the fetus.

35 General conclusions Piglet mortality significantly influences pig production Piglet mortality is primary a developmental issue with problems arising during prenatal development Energy reserves, particularly glycogen, initially play an important role in survivability of piglets Colostrum/milk from the sow quickly takes over as the primary nutrient source and plays a further role on survivability and growth of piglets Meishan piglets are a good model for developmental potential in regards to energy reserves during late prenatal and early neonatal periods

36 Future directions using Meishan pigs I. Assess genotypic differences in glycogen metabolism, gut and muscle development during the neonatal period II. Assess genotypic differences in piglet activity & sow nursing ability during lactation III. Assess genotypic differences in sow energetics, lactation performance, and piglet growth

37 Acknowledgements Jeff Vallet Joe Ford Brad Freking Ron Christenson William Oliver Bob Cushman Harvey Freetly Tommy Wheeler Steven Shackelford Lea Rempel Suzy Hassler Jere Noel Shanda Watts Al Kruger Dave Sypherd Mike Judy Chris Haussler Jeff Waechter Swine Crew Abattoir Crew Funding provides by CRIS Project # D

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