Caleb Lemley, Mississippi State University Aug. 20, 2019

2019 ARSBC, Knoxville, Tenn. 1

Managingthepregnantfemale– fetalprogrammingCaleb O. Lemley, PhDDepartment of Animal and Dairy Sciences, Mississippi State University

DevelopmentalProgramming• The process through which a stimulus or

insult establishes a permanent response

• Developmental programming hypothesis• Exposure during a critical period in

development may influence later metabolic or physiological functions in adult life

PhenotypeClassic Animal Breeding Example

Phenotype = Genotype + EnvironmentEg. Milk production = Holstein genetics + Mastitis

PhenotypeFuture Animal Breeding Example

Phenotype = Genotype + EnvironmentEg. Yield grade = Angus genetics + Uterine environment

“Farmers, ranchers and animal scientists know more about how nutrition affects fertility in cows, pigs and other commercially important animals than fertility experts know about how it affects reproduction in humans. There are small hints scattered across medical journals, but few systematic studies of this crucial connection in people”

1999 2002 2010

Caleb Lemley, Mississippi State University Aug. 20, 2019

2019 ARSBC, Knoxville, Tenn. 2

Livestock• Developmental programming known for decades prior to

epidemiological studies in humans. • How does developmental programming negatively

impact animal agriculture?• If we fully understand the process, could we develop

positive interventions to impact agriculture?

• Rationale: Majority of mammalian livestock used for meat production spend 30% of their life within the uterus being nourished solely by the placenta.

0102030405060708090

100

Percent Time in Each Phase of Beef Production from Conception to Harvest

In Utero (33%)

Nursing (28%)

Stocker (18%)

Finishing (21%)

Developm

ental Plasticity

Womb

Tomb

Percentage of total lifetime in each phase of beef productionfrom conception to harvest (womb to tomb). Nearly a third oflife is spent developing in utero when the fetus is mostvulnerable to the environment because of increaseddevelopmental plasticity.

10principalsofDevelopmentalProgramming1) During development in the womb, there are critical periods of vulnerability to suboptimal conditions.

Vulnerable periods occur at different times for different tissues.

Bovine Fetal Growth

Time Line

InfluenceofPrepartumNutritionontheReproductivePerformanceofBeefFemalesandthePerformanceofTheirProgeny(Corahetal.,1975)2 Dietary Treatments Applied 100 days Prepartum 1.) Nutrient Restricted 2.) Adequately Fed

Major Results:1.) Birth weight: by 7% in progeny born to RES 2.) Mortality rate: (10% in RES; 3% in ADQ)3.) Weaning weight: by 8% in progeny born to RES4.) Puberty of heifer progeny born to RES by 19 days

Milk production was not different between two groups; progeny programmed in utero…

Sawalha et al. (2007) Animal. 1:151-157.

Surviving Low Birth Weight Offspring• Increased morbidity• Slow Postnatal Growth• Organ dysfunction (adult onset)

10principalsofDevelopmentalProgramming5) The placenta plays a key role in programming

Caleb Lemley, Mississippi State University Aug. 20, 2019

2019 ARSBC, Knoxville, Tenn. 3

PlacentalEfficiency=(Birthwt /Placentawt)

Birth

Wei

ght,

lb

Placenta Weight, lb

20

4

0

6

0

8

0

100

4 8 12 16 20

High PELow PE

Difficult to Select for PE?

What controls PE?

Blooddistributionduringpregnancy• Uteroplacental blood

flow increases dramatically to support the nutritional demands of the rapidly growing fetus

Rosenfeld, 1984

Model Fetal Wt

Placental Wt

Placental Vascularity

Gravid UtBlood Flow

Umbilical Blood Flow

Overfed Adolescent - 20-40% - 20-45% - 31% - 36% - 37%

Multiple Pregnancy - 30% - 37% - 30% - 23% ---

Heat-Stressed Adult - 42% - 51% --- - 26% - 60%

Underfed Adult - 12% --- - 14% - 25% NSE

Underfed Adolescent - 17% NSE - 20% --- ---

Adolescent vs. Adult - 16% - 26% - 24% --- ---

Maternal Genotype (Adult only)

- 44% -28% - 33% --- ---

ModelsofGrowthRestriction= NDSU models

Reynolds et al, J Physiology 572.1:51-58, 2006

TimingisEverything(Early)

Cain et al. 2017. Theriogenology. 87:9.

• Early nutrient restriction model for Southeast• Beef producers opting for low-input, forage-based

replacement heifer management programs • 2 Groups of Replacement Heifers (replicated Spring

& Fall)• Low-Input (LOW): ~ 50% of expected mature BW at

breeding• Conventional (CON): ~ 65% of expected mature BW at

breeding

• At 45 days post-breeding heifers were comingled with adequate nutrition

HeiferDevelopmentResults• No change in late term uterine blood flow, fetal growth, and

birth weight. • Ideally, LOW heifers had compensatory changes to uterine

blood flow…

Cain et al. 2017. Theriogenology. 87:9.

• Calf weaning weight decreased by 38 lb in LOW vs CON.

• Spring heifers had increased uterine blood flow, birth weights, and weaning weights compared to fall calving heifers.

TimingisEverything(Mid)

Lemley et al. 2018. J Anim Sci. 96:4823.

• Do we need to supplement feed ($) during an early to mid pregnancy nutrient restriction? • Will breed influence this “programming” response?

• Angus and Brahman heifers were randomly assigned to 100% (CON) or 60% (RES) nutrient requirements from days 50 to 180 of gestation.• Re-alimented to adequate fed from day 180 to term.

Caleb Lemley, Mississippi State University Aug. 20, 2019

2019 ARSBC, Knoxville, Tenn. 4

BloodFlowandFetalSizeLemley et al. 2018. J Anim Sci. 96:4823.

Re-alimentationofFeedBirth Weights Not Different

Weaning Weights Not Different

Hearth Girth in Restricted

From Birth à Weaning

AlternativeTherapeutics• Can we use dietary supplements (antioxidants) to

improve postnatal growth? • Melatonin is a strong antioxidant and hormone of

nighttime • Cost effective for producers• $0.02/head/day (purchased as powder)• $1.80/head to cover last third of pregnancy (90

days)

ExperimentalDesign• Holstein heifers were bred in January 2013 using

sexed semen. • Trained to Calan feeding system at 170 days of

gestation (June of 2013; heat index on the rise!).• Dietary treatments applied from d 190 of gestation

until d 262 of gestation (20 mg of melatonin or no melatonin) • Average gestation length was 275 ± 2 d.

DairyHeiferResults

Brockus et al. (2016)

DietaryMelatoninvsImplants• 32 heifers and 25 cows confirmed pregnant to TAI,

predominantly Angus breeding crossbreds.• Cattle were treated with 2 subdermal ear implants

containing 24 mg of melatonin each. • Implants were administered every 30 days, occurring

on day 180, 210, and 240 of gestation. The last implant was expected to provide melatonin until day 270 of gestation.

Caleb Lemley, Mississippi State University Aug. 20, 2019

2019 ARSBC, Knoxville, Tenn. 5

BeefCowResultsMcCarty et al. (2018)

CCR in MEL

BMI in MEL

Longer and Leaner Calves

P - valueItem CON MEL SE TrtBody weight, lb 431 488 16 0.006Scrotal circumference, cm 18.7 19.6 0.4 0.032

BullCalfMeasurementsat195days(weaning)

McCarty et al. (2018)

Range P - valueItem CON MEL SE MIN MAX TrtSpermatozoa x 106/mL 386.9 357.2 19.3 281.9 458.6 0.148Motility

Motility, % 57.0 71.4 7.2 43.6 76.1 0.066Progressive, % 42.7 53.6 6.1 28.9 70.8 0.096

MorphologyProximal droplet, % 8.7 5.8 2.9 1.2 20.5 0.356Distal droplet, % 9.0 6.3 1.1 3.2 14.1 0.033Bent tail, % 3.9 2.7 0.9 1.9 5.3 0.178Coiled tail,% 1.7 1.3 2.3 0.3 3.7 0.876

Semenanalysisofbullsat~13monthsofage FutureResearch

• Fall vs Spring calving heifers experiencing nutrient restriction and melatonin supplementation during late pregnancy. • Timing of melatonin supplementation during bull

development (in utero, pre-weaning, post-weaning). • Southeast model (T. Smith): Fall calving Angus with

early (May or before) hair shedding weaning heavier calves.

Conclusions• Insufficiencies during pregnancy, resulting in

reduced fetal development, are detrimental to beef cattle production • The timing of nutrient supplementation should be

considered relative to stage of pregnancy• First 3 months, Middle 3 months, and Last 3

months• Increased uterine blood flow during last 3 months

increased weaning weight and may improve bull development

Acknowledgments&Funding• MSU-Faculty

• Derris Burnett• Brian Rude• Heath King• Richard Hopper

Biophotonics Initiative #58-6402-3-018

• MSU-Graduate Students• Katelyn Brockus (M.S.)• Caitlin Hart (M.S.)• Megan Owen (Ph.D.)• Keelee McCarty (M.S.)