Fisiopatologa del periodo de transicin:

Fisiopatologa del periodo de transicin:

Dficits energticos durante el periodo vital e inmunosupresin

Dr. Vctor Absaln MedinaUniversidad de Pennsylvania

Periodo de transicinPrincipales caractersticasTres semanas prepartoReduccin en consumo voluntario de materia seca CVMSElevada concentracin de hormonas esteroideas Actividad ovrica bajaTres semanas postpartoCVMS reducidoDesconexin en el eje IGF-GHEnerga destinada para la produccin de lecheInmunosupresin

The importance of energy metabolism in the lactating dairy cowEnergy MetabolismMilk ProductionHealth-Liver (Trigs, genes)-Uterus (infection)Ovarian Function - early Ovulation

Reproduction/fertility during LactationButler, 2015Periodo Vital Das Pre-Parto Das Post-Parto-60-30030Transicin Periparturient transition periodCascade of metabolic and physiological changes important for milk production, health and future reproductive performanceCalving

-3 weeks 0 + 3 weeks Nutrient accrual body reserves and fetusRapid mobilization of lipid & protein stores for energy metabolism-lactation

Butler, 2015Resumption of ovulation postpartum requires recovery from pregnancy and parturition

GonadotropinsLH & FSHPulsesGluconeogenesisFatty Acid Oxid.IGF- IRemoval of suppression by hormones of pregnancyButler, 2015Postpartum patterns of follicular development and estradiol production

Butler, 2015Utilizacin de Nutrientes

Cambios crnicosHomeorhesis del Periodo VitalParto y PuerperioLactognesisGalactopoiesisLiplisisGluconeognesisAA + GlucogenlisisFeto-Placenta y teroDietaReservas hepticas y muscularesReservas de tejido adiposoRequerimientos Feto-placentarios y UterinosMetabolismo FetalMetabolismo tero-placentaGlucosa 50-60%va lactato intermediarioAcetato10-15%cidos grasos y cuerpos cetnicosTransporte limitadoAmino cidos30-40%MP 3x NPEjemplo 74 g/d para deposicin de protena requiere 220 g/d5% requerimientos de energa destinados para deposicin de grasaPlacentomas, endometrio y miometrio20% del peso total del tero grvido35-50% consumo de O265% de la glucosa absorbidaGlucosa30-40% conversin a lactatoCirculacin materna (carncula y tero) y fetal (reciclado).

Distribucin de Nutrientes: recursos maternos VacaFetoGlucosa46%Amino cidos72%Acetato12%Estado nutricional: efectos de la energa y protena Requerimientos energa y nitrgenoPlacentaDifusin facilitadaGradiente responsable en cambios maternos de glicemiaRumiantes son susceptibles a hipoglicemia en el ultimo trimestre de gestacinMala nutricin tiene efectos sobre la distribucin de amino cidos dirigidos a la miognesisAdaptacin MaternaIncremento de la produccin de glucosaSustratos glucognicos endgenosAmino cidos, glicerol, lactato Estos cambios son exacerbados en un escenario de mala nutricinAdaptacin Materna: Preparto

Catabolismo MuscularLactato MuscularCiclo de CoriCompensar (insuficiente) lactato placentario Disminucin de Acetato disponibleDebido a CVMS disminuidoUtilizacin del tejido adiposoNEFAs Cuerpos cetnicosAumento an cuando se alimentan de la mejor maneraBHBAAumenta cuando hay una oxidacin heptica incompleta de NEFAs Hiperplasia e hipertrofia heptica para aumentar la sntesis de protenaReduccin de catabolismo heptico proteicoBUN bajoAdaptacin Materna: Peri-parto

Comparacin de valores estimados requeridos (uterinos vs. mamarios) a los 250 das de gestacin. Bell, 1995Tejido adiposo: cidos grasosEstimulacin adrenrgicaG-proteinAdenylciclasacAMPPKAHSLPerilipinsLiplisisLipognesis reducida Resistencia a insulinaTejido muscular tambinMovilizacin de NEFA y AAGlucosa moderada

Cambios en Epitelio del RumenDietas altas en energaNFC 43%22% AlmidnProceso fisiopatolgicoCuando no hay aclimatacin suficienteDesconexin GH-IGF-IApoptosis de las clulas epiteliales ruminalesMenos produccin y absorcin de cidos grasos Riesgos de acidosis ruminalDisminucin apetitoYa sabemos lo dems!

Steele et al. 2015Eventos durante el peri-parto

Aumento de estrgenos Perdida de apetitoRespuesta adrenrgicaLiplisisNEFA y GlicerolGlucosa, AA y Acetato dirigidos hacia feto y glndula mamariaFormacin de cuerpos cetnicosCuerpos Cetnicos

Acetyl-CoA AcumuladaAlmacenada en forma de Acetoacety-CoAMatirx mitocondrial2 Acetyl-CoACuerpos cetnicos llegan a tejidos extra hepticosCuerpos Cetnicos

Niveles altos en aceto-acetato y BHBABajan el pH causando acidosisConcentraciones altas de CCResultan en cetosis

As early as 3 weeks prepartum, differences in DMI, insulin, IGF-I and EBAL (OV vs. NOV)

Follicle grows to similar large size Estradiol production from large follicle ( CR% = 23 vs. 51; Galvao and Santos, Reprod.Dom.An. 45:439,2010.CR%BCS lossPregnancy %Odds RatioPregnancy loss, %> 1 unit28Referent20.5< 1 unit371.414.5No Change421.710.7BCS change from calving to AI (70 DIM; 6400 cows)Santos et al., An.Reprod.Sci. 110:207, 2009CR % among quartiles milk yield to 90 DIM NSActividad OvricaConsumo voluntario de materia seca es claveEventos por tejidosOvarioIndependiente del estado energticoCrecimiento folicular en la primera semana postpartoOvulacin, atresia o quisteHgado Resistencia a insulinaIGF-IE2 (Folicular)

Beam y Butler, 1999Actividad InmunolgicaEstallido RespiratorioDisminucin PMN prepartoRetencin de placentaMetritisCalidad de PMN reducidaReservas de glucgeno en PMN reducidasEstallido respiratorio insuficienteEndometritis subclnica (30-40 post-parto)

Hoeben et al. 2000Trabajo en el Trpico Mexicano

Trabajo en el Trpico Mexicano

Trabajo en el Trpico Mexicano

Trabajo en el Trpico Mexicano

Tercer trimestre de gestacinPeriodo crticoDeficiencias energticasProtena?Conclusiones preliminaresSuplementacin energtica necesaria en este periodo principalmenteBuena alimentacin desde primer partomejor rendimiento productivoAbsaln-Medina et al. 2011 Bajo rendimiento productivo: ResumenReproduccinRetencin placentaria y endometritisInmunosupresinDesconexin del eje ST-IGF EsteroidognesisCapacidad folicularCapacidad del vuloCalidad del endometrioProduccin de lecheDesconexin del eje ST-IGF Mantenimiento de las clulas mioepiteliales

ReferenciasPathways to Pregnancy and Parturition. Second Revised Edition. P.L. Sengler. 2003.

Anatomy and Physiology of Farm Animals. R. D. Franson., W. L. Wilke., A.A. Fails. 2009. Seventh Edition.

Lehninger Principles of Biochemestry. D. L. Nelson., M. M. Cox. 2008. Fifth edition.

Diapositivas en Ingls: Contribucin por el Dr. W.R. Butler de la Universidad de Cornell en los EE.UU.RNAregressiondaycowdietovplasmaIGF (ng/ml)GHR RNAIGF RNAIGF (micrograms/ml)-216108Ay3.6807594.801006-216238An130.5495.8834812.14355213.0549-216377Ay89.7738.4366492.5727958.9773-216437Ay72.2734.3570054.0840587.2273-216072Ay98.8373.8548372.5491279.8837-216258Ay133.7853.6342810.51823213.3785-216244Bn88.1770.8745852.3294738.8177-216407Bn88.2612.2449192.1336648.8261-216022Bn55.2012.0023160.3257125.5201-216071Bn150.5643.8906112.87454415.0564-216350By101.0094.2085896.30575910.1009-216446Bn111.3322.2974021.68958611.1332-215306Bn67.8475.1574933.3480866.7847-215798By177.2065.9381087.74538317.7206-216457Cy140.6473.4342543.19688514.0647-216003Cn135.13511.183798.20594813.5135-216348Cy85.9951.2804670.808518.5995-216326Cn115.6782.8878524.76783211.5678-215814Cn70.5753.1311011.4339597.0575-216181Cn106.8886.6422110.0561110.68881610822.0632.0994381.3043552.2063GHRpIGFIGFRNA1623843.5290.3321720.1403084.3529-214.3634954510.63.594511051637733.3440.1020020.740553.334410.57444553.40.82810891643726.2271.8747131.6586432.6227211.35747353.61.25051191607229.130.2354250.3745782.9131625840.5040.7071080.4988474.05041624432.4770.9033371.986193.24771640748.6420.1244232.5966774.86421602221.3260.8341260.3639142.13261607134.2430.1524770.157493.42431635021.7390.6506721.1809952.17391644631.4390.2049480.2952483.14391530645.9250.0374210.1017674.59251579838.0620.757860.5433693.80621645738.4540.2442890.1786243.84541600346.9810.2851920.6628114.69811634831.0450.5000010.9704123.10451632625.9810.5770081.040062.59811581446.6750.3806850.4263184.66751618134.9360.8605491.3410223.493621610835.4590.2186460.261223.545921623842.210.6155740.1425964.22121637734.1960.7955380.4638313.419621643729.7271.6509961.44062.972721607215.9380.0989840.0900381.593821625858.6030.2751590.1524785.860321624432.0861.9543241.3134283.208621640746.3030.5188290.7773664.630321602218.0082.4594521.0000021.800821607132.280.5528640.5285093.22821635038.346.2912067.1602173.83421644627.8240.614150.7303532.782421530672.4330.5182320.4659797.243321579847.6361.576441.1434054.763621645738.3811.5583260.5837143.838121600332.1661.1381341.1755513.216621634844.6283.5064311.3043554.462821632620.9850.7371330.5285092.098521581436.7611.0942961.8574673.676121618132.4810.6343413.890623.2481

RNAregression4.3634954510.63.594511050.57444553.40.82810891.35747353.61.2505119

GHRpIGFIGFRNA

IGFbyovstatus000000000000000000000000000000000000000000000000000000000000

IGF (micrograms/ml)Fold Difference in IGF RNAPlasma IGF (micrograms/ml)

IGFbydiet000000000000000000000000000000000000000000000000000000000000

IGF RNAFold Difference in GHR RNAFold Difference in IGf RNA

Insulinbyovstatus107.0763109.391497.7514116.436594.09746118.190894.93237111.789390.48375103.178984.1540897.9673381.8526793.7101177.07294.4353370.8669273.4651165.3355975.8144553.8051765.7766637.3508331.1742251.2117536.2771155.2394244.0436753.1299250.2583449.8337541.2701141.942538.0445640.6853333.3907837.7033333.46133.8805833.6447832.9866735.0703336.2037538.10089

NonovulatoryOvulatoryDays Relative to CalvingPlasma IGF-I (ng/ml)

Insulinbydiet96.0444110.25119.36375109.4678333333107.34562598.3585111.3328333333107.29287590.8516107.9598333333105.88537588.745694.419142857197.62012595.4291.946285714391.347586.191833333391.395714285784.2402585.321833333394.095571428674.76937586.326333333373.47871.78362570.495666666773.985428571465.17412571.177666666766.863285714359.83748.485532.97934.23162537.345333333338.900571428646.512549.438549.206142857149.15262553.600333333346.697857142950.22987560.193333333339.484857142949.22449.87542.200857142941.16037536.83735.398571428640.76587535.80432.153428571440.14837534.554666666732.66535.57362532.687666666731.909142857134.511535.336166666736.720142857139.3637534.2336666667

Diet ADiet BDiet CDays Relative to CalvingPlasma IGF-I (ng/ml)

E2 by ov status0.70044444440.86057142860.66510.845750.59581818180.6460.62081818180.7601250.6290.65622222220.70091666670.66844444440.66811666670.69911111110.601750.7480.47741666670.64155555560.53433333330.48977777780.49433333330.44311111110.28158333330.30744444440.3270.23588888890.19183333330.20488888890.23383333330.20066666670.23183333330.22811111110.24416666670.28355555560.27508333330.33966666670.23250.33144444440.260.25755555560.3820.3080.339250.3435555556

NonovulatoryOvulatoryDays Relative to CalvingPlasma Insulin (ng/ml)

Sheet40.87440.67371428570.811.01366666670.61150.610750.77333333330.5218750.58140.7310.654750.65720.6840.6226250.61416666670.70928571430.6273750.74050.8060.57030.68416666670.69014285710.6610.6390.66671428570.47950.50.66328571430.467750.40583333330.55428571430.408750.46166666670.39257142860.209750.28666666670.35285714290.2111250.31466666670.23285714290.1483750.22150.23457142860.2146250.20883333330.25314285710.18850.25916666670.33857142860.1868750.26950.40757142860.217250.29450.32828571430.217750.28883333330.28328571430.2138750.29066666670.46528571430.24050.36250.39542857140.29150.3438333333

Diet ADiet BDiet CDays Relative to CalvingPlasma Insulin (ng/ml)

GHR mRNA by diet3.12054545452.50533333330.35818181820.2020.08118181820.22388888890.10981818180.34611111110.32709090910.89244444440.31681818181.49311111110.74163636361.80766666671.04954545452.38855555560.58009090911.72388888891.3381.1684444444

NonovulatoryOvulatoryDays Relative to CalvingPlasma Estradiol (pg/ml)

GHR mRNA by ov status

IGF RNA by diet5.3493690.82932030.66588533.3267530.4581581.8106874.7599460.47462071.444777

Day -21Day 1Day 21Fold Difference in GHR-1A mRNA

575BP4.1996154.5637940.42657620.75517470.98521171.81246

NonovulatoryOvulatoryDays Relative to CalvingFold Difference in GHR-1A mRNA

GHR all cows2.7781280.78621350.42512723.3440260.90320621.6399074.7448740.76987451.556703

Day -21Day 1Day 21Fold Difference in IGF-I mRNA

IGF RNA all cows13.6166711.611.633311.2333329.7666724.93332.8166676.73.7833331.93.2666672.35

abbabaaaaaaaDay -21Day 1Day 21Arbitrary Units

IGF all cows bydate4.3634950.57444551.357473

abbFold Difference in GHR-1A mRNA

BPtable3.5945110.82810891.250512

abbFold Difference in IGF-I mRNA

GHRIGFtable108.089234.7037137.01681

abbPlasma IGF-I (ng/ml)

GHRIGF and plasmaIGFallcowsIGFBP-3S.E.IGFBP-2S.E.IGFBP-1S.E.IGFBP-4S.E.Day -2113.621.8411.233.532.820.7051.90.414Day 111.61.8429.773.536.70.7053.270.414Day 2111.631.8424.933.533.780.7052.350.414

ins and igfGHR-1AIGF-IGHR-1AS.E.IGF-IS.E.OVS.E.NOVS.E.OVS.E.NOVS.E.Day -214.250.3773.590.413Day -214.310.64.20.543.620.553.570.5Day 10.590.3770.830.413Day 10.80.60.430.540.830.550.830.5Day 211.340.3771.250.413Day 211.770.60.990.541.40.551.130.5Day -214.314.2Day 10.80.43Day 211.770.99

ins and igf (2)4.3634953.5945110.40.40.40.40.57444550.82810891.3574731.250512

GHR-1AIGF-I mRNAFold Difference in mRNA

worksheets107.0763109.39140.70044444440.860571428697.7514116.43650.66510.8457594.09746118.19080.59581818180.64694.93237111.78930.62081818180.76012590.48375103.17890.6290.656222222284.1540897.967330.70091666670.668444444481.8526793.710110.66811666670.699111111177.07294.435330.601750.74870.8669273.465110.47741666670.641555555665.3355975.814450.53433333330.489777777853.8051765.776660.49433333330.443111111137.3508331.174220.28158333330.307444444451.2117536.277110.3270.235888888955.2394244.043670.19183333330.204888888953.1299250.258340.23383333330.200666666749.8337541.270110.23183333330.228111111141.942538.044560.24416666670.283555555640.6853333.390780.27508333330.339666666737.7033333.4610.23250.331444444433.8805833.644780.260.257555555632.9866735.070330.3820.30836.2037538.100890.339250.3435555556

&APage &PNOV IGF-IOV IGF-INOV InsulinOV InsulinDays Relative to ParturitionIGF-I (ng/ml)Insulin (ng/ml)

Sheet2107.0763109.39140.70044444440.860571428697.7514116.43650.66510.8457594.09746118.19080.59581818180.64694.93237111.78930.62081818180.76012590.48375103.17890.6290.656222222284.1540897.967330.70091666670.668444444481.8526793.710110.66811666670.699111111177.07294.435330.601750.74870.8669273.465110.47741666670.641555555665.3355975.814450.53433333330.489777777853.8051765.776660.49433333330.443111111137.3508331.174220.28158333330.307444444451.2117536.277110.3270.235888888955.2394244.043670.19183333330.204888888953.1299250.258340.23383333330.200666666749.8337541.270110.23183333330.228111111141.942538.044560.24416666670.283555555640.6853333.390780.27508333330.339666666737.7033333.4610.23250.331444444433.8805833.644780.260.257555555632.9866735.070330.3820.30836.2037538.100890.339250.3435555556

&APage &PNOV IGF-IOV IGF-INOV InsulinOV InsulinDays Relative to ParturitionIGF-I (ng/ml)Insulin (ng/ml)

Sheet3IGF bv ovulation statusIGF by dietIGF all cows by dateInsulin by ovulationstatusInsulin by dietNOV IGF-IOV IGF-IDiet ADiet BDiet CNOV InsulinOV InsulinDiet ADiet BDiet C-21107.0763109.391496.0444110.25119.36375Day -21108.08920.70044444440.86057142860.87440.67371428570.81-1997.7514116.4365109.4678333333107.34562598.3585Day 134.703710.66510.845751.01366666670.61150.61075-1794.09746118.1908111.3328333333107.29287590.8516Day 2137.016810.59581818180.6460.77333333330.5218750.5814-1594.93237111.7893107.9598333333105.88537588.74560.62081818180.7601250.7310.654750.6572-1390.48375103.178994.419142857197.62012595.420.6290.65622222220.6840.6226250.6141666667-1184.1540897.9673391.946285714391.347586.19183333330.70091666670.66844444440.70928571430.6273750.7405-981.8526793.7101191.395714285784.2402585.32183333330.66811666670.69911111110.8060.57030.6841666667-777.07294.4353394.095571428674.76937586.32633333330.601750.7480.69014285710.6610.639-570.8669273.4651173.47871.78362570.49566666670.47741666670.64155555560.66671428570.47950.5-365.3355975.8144573.985428571465.17412571.17766666670.53433333330.48977777780.66328571430.467750.4058333333-153.8051765.7766666.863285714359.83748.48550.49433333330.44311111110.55428571430.408750.4616666667137.3508331.1742232.97934.23162537.34533333330.28158333330.30744444440.39257142860.209750.2866666667351.2117536.2771138.900571428646.512549.43850.3270.23588888890.35285714290.2111250.3146666667555.2394244.0436749.206142857149.15262553.60033333330.19183333330.20488888890.23285714290.1483750.2215753.1299250.2583446.697857142950.22987560.19333333330.23383333330.20066666670.23457142860.2146250.2088333333949.8337541.2701139.484857142949.22449.8750.23183333330.22811111110.25314285710.18850.25916666671141.942538.0445642.200857142941.16037536.8370.24416666670.28355555560.33857142860.1868750.26951340.6853333.3907835.398571428640.76587535.8040.27508333330.33966666670.40757142860.217250.29451537.7033333.46132.153428571440.14837534.55466666670.23250.33144444440.32828571430.217750.28883333331733.8805833.6447832.66535.57362532.68766666670.260.25755555560.28328571430.2138750.29066666671932.9866735.0703331.909142857134.511535.33616666670.3820.3080.46528571430.24050.36252136.2037538.1008936.720142857139.3637534.23366666670.339250.34355555560.39542857140.29150.3438333333E2 by ovulatory statusNonovulatoryOvulatory33.12054545452.505333333350.35818181820.20270.08118181820.223888888990.10981818180.3461111111110.32709090910.8924444444130.31681818181.4931111111150.74163636361.8076666667171.04954545452.3885555556190.58009090911.7238888889211.3381.1684444444GHR by dietGHR by ovulatory statusGHR all cowsIGF all cows by dateDiet ADiet BDiet CNonovulatoryOvulatoryDay -214.363495-215.3493693.3267534.759946-214.1996154.563794Day 10.5744455Day -21108.089210.82932030.4581580.474620710.42657620.7551747Day 211.357473Day 134.70371210.66588531.8106871.444777210.98521171.81246Day 2137.01681IGF RNA by ov statusIGF RNA all cowsGHR-1AIGF-I mRNAplasma IGF-IIGF RNA by dietNonovulatoryOvulatoryDay -213.594511Day -214.3634953.594511108.0892Diet ADiet BDiet CDay -213.5734973.620195Day 10.8281089Day 10.57444550.828108934.703712.7781283.3440264.744874Day 10.82834590.8278192Day 211.250512Day 211.3574731.25051237.016810.78621350.90320620.7698745Day 211.1282161.3999840.42512721.6399071.556703BP by timeBP-3BP-2BP-1BP-4Day -2113.6166711.233332.8166671.9Day 111.629.766676.73.266667Day 2111.633324.93333.7833332.35