Kim Vonnahme, PhD, conducts research on developmental programming at North Dakota State University.
Kim Vonnahme, PhD, conducts research on developmental programming at North Dakota State University.

We know the importance of colostrum at birth, good calf nutrition and sound weaning protocols in assuring calf health. We’re now learning more, however, about how the cow’s nutritional status during gestation can affect the expression of genes in the developing calf, influencing immunity, growth and reproduction over the calf’s entire lifetime. This phenomenon, known as “fetal programming” or “developmental programming,” has been documented in humans and other animals but is not well understood, and scientists currently are exploring implications for cow nutrition and cattle production.

During a recent veterinary nutrition conference hosted by Purina Animal Nutrition at the company’s research farm outside St. Louis, Ron Scott, PhD, director of beef research, outlined the current understanding of fetal programming and the importance of year-around cow nutrition for production of healthy, productive calves.

The concept of fetal programming involves the process of “epigenetics,” in which environmental factors cause genes to express themselves differently even though the genes themselves do not change. Scott described several studies in human medicine that helped define fetal programming and demonstrate its effects. In England, for example, poverty and malnutrition in certain regions of the country during the early 20th century led to high incidence of light birthweights for babies. Later, in the 1960s and 1970s, scientists found a high rate of coronary heart disease in the adults born in those areas during that period.

During World War II, in the winter of 1944, the besieged people of the Netherlands experienced the “hunger winter,” suffering severe famine for three months. Scientists later studied the health of adult children of Dutch women who had been pregnant during that period. They found those who had been in their first trimester of gestation during the famine were more likely than average to be obese as adults, suffer cardiovascular disease and have high LDL cholesterol. Those who were in their second trimester were more likely to be glucose intolerant and suffer kidney disease, while those who were in their third trimester were more likely to have asthma.

As for cattle, Scott points out that their diets, particularly in beef herds, can vary considerably in nutritional quality over the course of a year, and forage energy typically is lowest during the third trimester when cow requirements are greatest. He also noted that cows are eating for two, or three, every day of the year, since they are lactating, gestating or both. Doctors, he notes, do not advise women to lose weight during pregnancy. And yet, in our production systems we typically expect the gestating cow to lose weight and gain weight over the course of the year.

Placental development

Conventional wisdom suggests the third trimester is the most critical for development of the calf, since 75 percent of fetal growth takes place during that period. However, placental and vascular development regulating blood flow to the fetus occurs during the first and second trimester, as do organ differentiation and determination of the number of muscle fibers.

North Dakota State University animal scientist Kim Vonnahme, PhD, has conducted a variety of studies into developmental programming in cattle and sheep, looking at the effects of dietary restrictions at different stages of gestation. Research has shown, she says, that the large increase in transplacental exchange, which supports the exponential increase in fetal growth during the last half of gestation, depends primarily on the dramatic growth of the uteroplacental vascular beds during the first half of pregnancy. Functional fetal and uteroplacental circulation is one of the earliest events during embryonic and placental development, and fetal growth restriction is highly correlated with reduced uteroplacental growth and development.

Vonnahme says any detrimental effects of maternal nutrition during this critical establishment of the maternal-fetal vascular systems would impact the ability of the fetus to acquire the proper amount of nutrients and oxygen. All of the respiratory gases, nutrients and wastes that are exchanged between the maternal and fetal systems are transported via the uteroplacenta, so it not surprising that fetal growth restriction appears highly correlated with reduced uteroplacental growth and development.

Vonnahme and other researchers are exploring the potential for modifying uterine blood flow and nutrient transfer capacity in the placenta, possibly using novel therapeutic agents to improve placental function and thus decrease the incidence of morbidity and mortality as well as suboptimal offspring growth performance.

The NDSU team has investigated the role that realimentation, protein supplementation and melatonin supplementation has on uteroplacental blood flow and vascular reactivity of the placental arteries. In their studies, they have used Doppler ultrasonography as a means to monitor uteroplacental  blood flow at different time points during pregnancy.

In cattle, Vonnahme and her team have found that nutrient restriction from early to mid-pregnancy, such as from day 30 to 140, does not alter uterine blood flow. However, upon realimentation, the uterine artery blood flow increases in those cows that were previously restricted, but only to the horn in which the calf is housed. Interestingly, she says, it appears that realimentation alters the growth trajectory of the bovine placenta. The team is continuing studies to determine which portions of the placenta (i.e., maternal or fetal) may contribute to compensatory prenatal growth of the fetus.

Mid to late gestation

While early placental development is important in the overall development of the fetus, Vonnahme says her research has shown the cow can compensate better than earlier believed during early gestation, maintaining blood and nutrient flow to the placenta even when her diet is restricted.

Research indicates that during mid to late gestation, when the fetus experiences rapid growth, restrictions in the cow’s nutrient status or other stressors could have more profound effects on long-term calf performance. Vonnahme also notes that while placental growth slows during the last half of gestation, placental function increases dramatically, with uterine blood flow increasing approximately three- to four-fold to support the exponential rate of fetal growth.

Vonnahme notes that several recent University of Nebraska studies examined late-gestation protein supplementation in cows gestated on range where crude protein of forage was below 6 percent. Calves from the cows that were protein supplemented during late gestation had similar birthweight but increased weaning weight compared to those from cows that were not supplemented, indicating the protein supplementation enhanced growth after birth. Furthermore, the pregnancy rates in heifer calves born from protein-supplemented cows were enhanced, with a 93 percent pregnancy rate compared to 80 percent for control cows.

Ongoing studies at NDSU are investigating how protein supplementation during late gestation can impact uterine blood flow. For the past two years, Vonnahme and her team have investigated how protein supplementation, in the form of dried distillers’ grains with soluble (DDGS), can impact uterine blood flow. In one study, using DDGS with a low-quality forage source appeared to reduce uterine blood flow compared to control cows. In a more recent study, Vonnahme’s team demonstrated that when DDGS is given with a corn-stalk forage base, uterine blood flow increased. “We are investigating how specific nutrients differed between these two studies in order to tease apart the mechanism that may be impacting how protein influences uterine blood flow in the beef cow,” she says.

Vonnahme also notes that early research results suggest supplementation and cow body-condition scores during late gestation influence Immunoglobulin G (IgG) concentrations in the dam’s colostrum and possibly her milk production through gestation.

Scott says that in a Florida trial looking at heat stress in dairy cows, researchers provided fans and sprinklers for one group of cows through gestation and no cooling for another group. They found that heat stress during gestation decreased serum IgG in calves, impaired lymphocyte proliferation in calves and decreased milk production in offspring.

Developmental programming also could affect the calf’s susceptibility or resistance to bovine respiratory disease. Vonnahme notes the precise relationship between alveolar and vascular development during fetal and early postnatal life and the mechanisms that coordinate lung vascular growth and alveolarization are uncertain. However, research shows that vascular endothelial growth factor, produced from airway epithelial cells, plays a major role in vascular growth development during fetal life. These findings suggest a link between lung vascular development and alveolar growth, further suggesting that disruption of normal vascularization may contribute to altered alveolarization and, thus, lung function. It is possible that gestational nutrient restriction could increase susceptibility of cattle to respiratory disease during later life such as in the feedlot.

Researchers continue to study fetal programming in cattle, hoping to better identify key nutrient requirements at various stages of gestation and develop targeted nutritional recommendations based on those requirements. Vonnahme says current research results have generated some general recommendations for providing cows with adequate energy and protein, particularly in mid to late gestation. Those more-detailed recommendations for levels of key nutrients at specific stages of gestation will require further study.