Obesity Studies on Pregnant Sheep

This experiment was conducted at the University of Adelaide in South Australia, and supported by the Brailsford Robertson Trust and the National Health and Medical Research Council.

Objective

Women entering pregnancy with a high body weight and fat mass (BMI) have babies who are at increased risk of becoming overweight or obese in later life. Obesity is expensive to society and can lead to a multitude of secondary illnesses in the individual. In human studies, it is difficult to isolate the impact of a high maternal body weight during the periconceptional period (before and shortly after conception) from the impact of a high maternal body weight during later gestation on the development of body fat in the offspring.

Researchers have therefore attempted to isolate this variable by recreating the condition in sheep – presumably for the benefit of humans. The aim of this experiment was to determine whether maternal over-eating during the periconceptional period 'turned on' fat-development genes in the offspring and led to increased body fat at birth; and whether dietary restriction could reverse these changes.

What Happened to The Animals

Eighty-nine adult South Australian Merino ewes were used in this study. They were randomly allocated to one of two groups: 23 to the 'Donor' group, and 63 to the 'Surrogate' group. This accounts for 86 sheep. The fate of the other 3 ewes is not known. This number does not include the 63 lambs born and killed as a result of this study. All procedures were approved by the University of Adelaide Animal Ethics Committee.

At the beginning of the study, 23 'Donor' ewes were isolated in an enclosed shed and confined to pens. They were fed pellets that provided 100% of their energy requirements. After 20 days of acclimatizing to the diet, they were randomly assigned to one of the following groups:

CC (control-control) – 6 ewes were fed 100% of their energy requirements for 5 months. This group represented mothers entering pregnancy at a normal weight.
CR (control-restricted) – 6 ewes were fed 100% of their energy requirements for 4 months, then had food restricted to 70% for 1 month. This group represented mothers who were effectively entering pregnancy underweight.
HH (high-high) – 6 ewes were allowed to eat freely, without restriction (consuming around 170–190% of their energy requirements) for 5 months. This group represented mothers who were obese at the time of pregnancy.
HR (high-restricted) – 5 ewes were allowed to eat freely, without restriction for 4 months, then had food restricted to 70% of their energy requirement for 1 month. This group represented mothers who were obese but dieting just before pregnancy.

The reproductive cycles of all the 'donor' ewes were synchronized by dosing them with intravaginal pessaries, and a number of hormone injections.

Semen was collected from a ram, and researchers performed laparoscopic surgery on all the ewes to artificially inseminate them . They were lightly sedated during the procedure. 6-7 days later the ewes were anaesthetized and researchers performed laparoscopic surgery again, this time to remove the embryos.

A group of 63 'surrogate' ewes of normal weight were introduced to the study. Researchers also performed laparoscopic surgery on these ewes to implant a single embryo (taken from the above 'donor' group) into the uterus of each surrogate. These ewes were then fed 100% of their energy needs for the entire pregnancy and allowed to give birth naturally.

To measure blood glucose and fatty acid concentrations in the blood, up to 4 blood samples were taken from each ewe at different times throughout the study. Blood samples were also taken from the lambs on the day of birth, and again at four months of age when they were weighed and killed by lethal injection.

After death, fat which had accumulated around the lambs' organs and skin was dissected and weighed to determine total body fat mass, fat mass surrounding the organs, and the fat mass deposited under the skin. Genetic material was extracted from the fat in order to study the fat-development genes of each lamb.

Results

It took more than $320,000 [1] in funding, more than 9 months time, and the death of at least 63 lambs to obtain the following results:

When ewes over-ate before and shortly after pregnancy, their weight and body fat ratio increased; as did that of their female offspring.

Overweight ewes bore offspring with a better ability to synthesize and store fat, particularly the female babies. This increased capacity did not seem to be caused by fat-genes being turned on.

Restricting the diet of overweight mothers reduced their weight and body fat ratio, and that of the offspring. It also reduced the lambs' adaptation ability to synthesize and store fat more efficiently.

Genes did not appear to be directly responsible for these mechanisms.

Why the Experiment Was Unjustified

Subjecting sheep to these experimental techniques and killing their lambs, purely for our own curiosity and perceived benefit, is ethically corrupt. This cruelty can never justified.

The scientific relevance of inducing obesity in sheep is also obscure and unjustifiable. Any similarities that humans and sheep may share are eclipsed by biological species differences and lifestyle factors, making it impossible to extrapolate the results of this research from sheep to people.

One must also question why this research was approved, funded and conducted despite the fact that human studies already existed. A large epidemiological enquiry had been conducted on humans 6 years earlier, finding that maternal obesity in early pregnancy more than doubles the risk of obesity in the offspring at 2 to 4 years of age (Whitaker, 2004). How could sheep studies be more relevant than human studies?

In addition, the US Nutrition Society states that human obesity is a multifactorial condition where "the major factors involved...seem to be dietary and physical activity habits". They believe the role of genes is secondary to these factors:

" These factors (diet and exercise) are affected by susceptible genes that in turn may influence energy expenditure, fuel metabolism, muscle fibre function and appetite or food preferences. However, the increasing rates of obesity cannot be explained exclusively by changes in the gene pool" (Alfredo, 2000).

So, if the purpose of this experiment was ultimately to benefit humans, the question must be asked...how could knowing the role of genes in sheep obesity further our knowledge of the human condition? It can't.

What Can You Do?

Please write to the National Health and Medical Research Council (NHMRC), asking them to stop funding animal experiments with your taxpayer dollars, and to instead fund epidemiological studies:

Prof. Warwick Anderson,

Chief Executive Officer,
NHMRC (MDP 100)
GPO Box 9848
Canberra, ACT 2601
Email:

And please write to the following to express your disappointment at such useless research:

Prof James McWha

Vice-Chancellor & President
The University of Adelaide, SA 5005
Email:

References

Alfredo Martinez J., 2000, Body-weight regulation: causes of obesity, Proceedings of the Nutrition Society, Vol. 59, pp337–345.
Rattanatray L., MacLaughlin SM., Kleemann DO., Walker SK., Muhlhausler BS., & McMillen IC., 2010, Impact of Maternal Periconceptional Overnutrition on Fat Mass and Expression of Adipogenic and Lipogenic Genes in Visceral and Subcutaneous Fat Depots in the Postnatal Lamb, Endocrinology, Vol. 151, pp. 5195-5205.
Whitaker RC., 2004, Predicting preschooler obesity at birth: the role of maternal obesity in early pregnancy, Pediatrics, Vol. 114, pp. e29–e36.

1 NHMRC research funding datasets 1990/2010 http://www.nhmrc.gov.au/grants/dataset/rmis/index.htm