Introduction to Fetal Programming

Dr. Jeff LehmkuhlerExtension Beef SpecialistAnimal & Food SciencesANR Update Fall 2013

Our Destination

Bovine Fetus Size

• 35 days

• 90 days

• 120 days

• 180 days

• 240 days

Barker Hypothesis

• Fetal Origins Hypothesis = Fetal Programming

• Traced back 1944 Nazi occupied Holland

• Calorie ration down to ~ 500 / d

• Offspring higher disease rates

Fetal Programming

• Maternal stimuli during pregnancy that can affect fetal development, as well as postnatal growth & health

• Maternal plane of nutrition influences / alters genetic expression of offspring

• In some species, lasts for several generations

• Provide opportunity of phenotypic variation in “Fixed” genotypes = Epigenetics

Epigenetics• Heritable changes in gene expression resulting

in alterations to chromatin structure– DNA methylation, Histone modification

(acetylation), noncoding microRNAs

http://micro.magnet.fsu.edu/cells/nucleus/chromatin.html

DNA Methylation Example

• Most DNA is methylated (CH3)– Regions not methylated are close to regulatory region

• Variation in methylation in different tissues

• S-adenosylmethionine = methyl donor influenced by diet

• Gestating Ewes restricted folate, vitamin B12, betaine, choline, methionine = obesity and impaired immune systems of progeny as adults

0

2

4

6

8

10

12

14

16

18

Oct Nov Dec Jan Feb Mar Apr May June July Aug Sept

2-year old

3-year old

5-year old

Estimated Net Energy Requirementsfor 2-, 3-, and 5-year old Cows

Calving

Months Since Calving1996 Beef NRC

Breeding Season

Wean

Mca

l/d

75% Fetal

Growth

First Trimester

Past Thoughts

• Dry, mid-gestational cow lowest nutritional needs

• Best time to “cheat” nutritionally

• Little fetal development = low nutrient need

• High supplementation during late gestation = heavier Birth Weights

Were We Wrong?

Placental Development

• Placentome = Cotyledons (Fetus) + Caruncles (Maternal)

• Growth occurs throughout gestation– First 2/3 of gestation primary growth

• Growth slows last trimester

• Blood flow 4.5-fold increase last ½ gestation

Nutrition & Placenta

• Nutrient restriction during early/mid-gestation– Lowered placentome weight

– Altered Vascularity of placenta

– Protein Supplementation on Day 190 = 2X blood flow

– Restriction reduces number of cotyledons, not caruncles

Fetal Organ Development

• Restricted Cows from day 30-125 of gestation– Fetuses had enlarged hearts & brains

– Feeding cows back to same condition score by day 220 of gestation = No differences by d 245

– Vascular of intestines, size of liver, lungs, pancreas, kidney, perirenal fat have also been shown to be impacted by nutrition of the dam

Maternal Nutritional Restriction on Fetal Muscle Development

Du et al., 2010 JAS

Muscle Fiber Numbers SETNo Increase after Birth

Muscle Development

• Animals born with set number of muscle fibers• Hypertrophy occurs after birth = Muscle fiber

size increases

• Low priority tissue = Susceptible to deficiency

Nutrient Restriction Skeletal Muscle

• Nutrition during pregnancy explained 20% of variation in birth weight (Robinson et al., 2013)

• Current research shows mixed results on muscle fiber number / diameter / carcass traits

What’s Been Reported – Few Examples

Restriction

• Early preg negative impact on sow placenta, myogenesis = growth, carcass (Foxcroft 2006)

• Protein Deficiency last 100d in cows = delayed puberty (Corah 1975)

• Calf BW reduced protein deficiency 2nd trimester (Micke 2010)

Overfeeding

• Ewes overfed had progeny that were leptin resistant = obesity (Long 2010)

• Heifers had lower milk production when suppl 1st Trimester (Sullivan 2009)

Supplementation

• Protein suppl lower morbidity (Mulliniks 2013)

• Suppl lower post-weaning morbidity (Larson 2009)

Timing of Cow Nutritional Plant & Impacts on Cattle

Light = Time of nutrition

Dark = When Impacts Progeny

So What = Theories

• We know – Birth weight, Colostrum, and placental development impacted

• We don’t know – Consistently what impact this will have on growth, fertility, health, etc…

• Add’l research in area will be forthcoming and help unravel

Recommendations?

• Manage diet to meet / slightly exceed nutritional requirements at various stages of production

• Critical points are late gestation / early lactation / early gestation– Often overlooked, hay quality ??, grass availability??,

fescue toxicity??

• Maintain BCS in 5-6 at critical points, Keeping Cows at Par / + Energy balance = Fertility

Mineral Update

• Matthews/Burris et al. Selenium Research– Support mix of organic / inorganic Se in mineral

• Grass tetany– Can occur in fall / winter– Lush pasture (N & K fertilizer) & cereal grain silage

• Spreadsheet comparison of IRM Rec to 4 oz

Forage Quality

• Going to be mixed = Recommend testing

• Late cuttings may be low quality

• Late Late cuttings may have vegetative regrowth to offset quality

• Second cuttings should be decent

• Silage quality likely quite good (high grain content)

Thoughts / Questions

Underfed Cow?