nutrigenomics and dairy cattle repro final paper

A review of past and current developments in nutritional research on improving dairy cattle

fertility and reproduction

Dylan Djani

November 20th, 2012

AVS H370 Principles of Animal Nutrition

Dr. Nathan Long

Nutrition and Reproduction 2

Abstract

Dairy cattle have undergone genetic selection geared at increasing milk production and

quality with little regard to other important traits, including those related to fertility. With a

marked decrease in dairy cattle fertility, researchers are using nutrigenomics technologies to

further the understanding of how nutrition affects gene expression in order to maximize dairy

cow fertility and balance out the negative effects of genetic selection. Before scientists

understood that nutrients have effects on reproduction by acting on interactions between the

somatotropic and gonadotropic axes, the fields of genetics, nutrition, and reproduction remained

relatively separated. As scientists’ understanding of physiological and molecular processes

developed together with molecular technologies, various scientific fields came together to create

the field of nutrigenomics, which offers many current research opportunities in the field of

animal science. By analyzing how exactly nutrients affect gene expression profiles and

interactions between the somatotropic and gonadotropic axes using nutrigenomics technology,

researchers will be equipped to design diets that cater towards dairy cow fertility as necessary.

Key Words

Dairy, cattle, reproduction, nutrition, technology, nutrigenomics

Introduction

Genetic selection is a prime example of the application of scientific knowledge to achieve

a goal, such as increasing milk production in dairy cattle. Consequently, along with the trend of

increased milk production due to genetic selection, health concerns including decreased fertility

in dairy cattle have also risen (Oltenacu and Broom, 2010). Research into correcting the issue of

decreased fertility in dairy cattle is ongoing and has become more intricate in conjunction with a

deeper understanding of physiology and genetics. Aside from simply trying to balance genetic


selection for milk production and reproductive traits, modern scientists are integrating scientific

disciplines into a systems biology approach that encompasses and extends beyond genetic

selection to include interactions between genetics, reproduction, and nutrition (McNamara,

2011). A fundamental concept to the systems biology approach is that nutrition and nutritional

metabolism intermediates are important players in interactions between endocrine system control

mechanisms, particularly the somatotropic and gonadotropic axes (Chagas et al., 2007).

Molecular biology and related emerging fields, such as metabolomics, are major contributors in

the application of the systems biology approach. These emerging fields bring associated

technologies that allow scientists to gain a better understanding of the exact mechanisms behind

nutrient metabolism and the effects of specific metabolites on growth and reproduction

(Drackley et al., 2006). Systems biology has ultimately led to the concept of nutrigenomics and

determining the best possible diets to match the genetics of dairy cows in order to maintain a

high level of production without the associated decrease in fertility; however, systems biology

and nutrigenomics have extensive applications that are not limited to improving fertility in dairy

cattle (Ghormade et al., 2011). Currently nutrigenomics is at the forefront of a wide range of

scientific research with many positive prospects for the future.

Literature Review

Negative impacts of genetic selection on milk production traits in dairy cattle include a

decrease in fertility, an increase in leg structural problems, and an increase in metabolic and

production-associated diseases (Oltenacu and Broom, 2010). Advances in molecular technology

have enabled scientists to develop a deeper understanding of nutrition, genetics, metabolism, and

reproduction in a framework where all of these fields overlap (Drackley et al., 2006). For

example, acute changes in the diet of cattle has been shown to have an effect follicular growth


through increasing blood levels of hormones such as insulin, insulin-like growth factor I (IGF-I),

leptin, and growth hormone (Armstrong et al., 2002). The mechanisms by which nutrition

affects growth, including growth related to production and reproduction, are a result of nutrients

and nutrient metabolites affecting how the gonadotropic and somatotropic axes in the body

interact (Chagas et al., 2007).

The gonadotropic and somatotropic axes are hormone pathways that are responsible for

metabolism, growth, and physiological function. The gonadotropic axis is involved specifically

with reproduction, such as ovarian follicular growth (Okamura and Ohkura, 2011). The

somatotropic axis involves the growth hormone, insulin-like growth factors I and II, and other

compounds related to the function and regulation of the growth hormone and insulin-like growth

factors (Renaville et al., 2002). Both the somatotropic and gonadotropic axes involve

interactions between the hypothalamus and pituitary glands, mediated by the growth hormone-

releasing hormone and somatostatin or the gonadotropin-releasing hormone respectively. These

compounds affect the amount of growth hormone or gonadotropins, including follicle-

stimulating hormone (FSH) and luteinizing hormone (LH), released by the pituitary gland into

systemic circulation. Within the somaotropic axis the growth hormone binds to target tissues

causing direct effects, such as increasing liver gluconeogenesis and protein synthesis, and

indirect effects via the release of insulin-like growth factors from target tissues that affect other

tissue metabolism, such as muscle metabolism of glucose, fatty acids, and amino acids.

Similarly, the gonadotropin-releasing hormone from the hypothalamus causes the release of

gonadotropin hormones, FSH and LH, which bind to target tissues and exert their effector

function, including follicular growth and ovulation in the female. The hypothalamus secretes the

gonadotropin-releasing hormone in pulsatile rhythms and large surges in accordance with the


female’s estrous cycle. For example, the hypothalamus releases a massive surge of

gonadotropin-releasing hormone directly prior to ovulation in order to trigger a massive release

of luteinizing hormone from the pituitary gland, which causes ovulation. The hypothalamic

secretions of the gonadotropin-releasing hormone are based on the effects of various signaling

molecules that carry information about the animal’s internal and external environments. An

example in terms of nutrition is how the hormone cholecystokinin positively stimulates

gonadotropin-releasing hormone pulses from the hypothalamus. Dietary changes in cattle have

an effect on the reproductive tract without exerting their effects directly through the

gonadotropic axis, but rather through the somatotropic axis by altering how cells and tissues

respond to hormones from the gonadotropic axis (Armstrong et al., 2002). Changes in the diet of

cattle that increase blood concentrations of growth hormone, IGF-1, and the hormone leptin have

effects on ovarian activity. IGF-1 interacts with insulin to stimulate the production of estradiol

in follicular cells of the ovary. Furthermore, changes in energy intake from the diet influences

the availability of IGF within ovarian follicles, which can affect the degree to which follicles

respond to the gonadotropin FSH.

Scientists attempting to improve dairy cattle production without negatively affecting

reproduction require a deeper understanding of how nutrition affects genetics and reproduction

(McNamara, 2010). In order to fully appreciate how nutrition, genetics, and reproduction

interact, other scientific fields including physiology and biochemistry must be incorporated to

create an integrated systems biology approach. Other technologies and fields such as genomics,

proteomics, and metabolomics must also be integrated into such a systems biology approach

because these fields tie together nutrition and reproduction on a molecular level and allow


scientists to determine which metabolites are required for optimal reproduction (Chagas et al.,

2007).

The emerging scientific field of nutrigenomics refers to the study of how the genetic

variation affects nutrient metabolism, including on the molecular level where nutrients directly

affect gene expression (Fenech et al., 2011). Nutrigenomics inherently incorporates nutrition,

biochemistry, genetics, genomics, transcriptomics, proteomics, and metabolomics to develop a

deeper understanding of interactions between nutrients and genes in order to create diets that

promote optimal health and minimize instances of disease. One study illustrated how a selenium

deficiency affected protein transcription, resulting in increased stress and suppressed

detoxification mechanisms due to altered gene expression; furthermore, interactions between

multiple nutrients and genes have been shown to contribute to causing complex diseases (Kore et

al., 2008). Research in nutrigenomics has many applications in animal science, with goals

including improved nutrition, production, reproduction and fertility, increased immunity and

resistance to diseases, and a better glimpse at the aging process of animals (Ghormade et al.,

2011).

Nutrigenomic technologies can be used to determine the effectiveness of specific

nutrients on specific metabolic processes related to reproduction and fertility, which offers a

chance at improving fertility issues in dairy cows. Nutrigenomic technologies include

microarray techniques that reveal the amount of specific mRNA in tissues and subsequently the

factors that control their transcription, which yields tremendous information for scientists when

analyzed in conjunction with gene expression profiles of dairy cows and will yield new concepts

to manage dairy cow nutrition and fertility (Beerda et al., 2008). Microarray technologies and

gene expression profiles eliminate the need for inducing nutrient deficiencies and using extreme


diets for research purposes (Dawson, 2006). Nutrigenomics is a versatile field that will be very

important in solving a multitude of problems in the future, including improving the decrease in

dairy cow fertility due to past genetic selection.

Discussion

Genetic selection has been employed within the dairy cow industry to select for traits that

have improved milk production and quality at the expense of other traits, a problem that has

partially manifested in the form of decreased fertility in dairy cows (Oltenacu and Broom, 2010).

Even with artificial insemination being the method of choice for reproduction in the dairy

industry, the available dairy cattle genetics nowadays is not widespread enough to tackle the

problem of decreased fertility by incorporating new genetics into farmers’ dairy herds. As other

scientific fields developed into their respective bodies of knowledge, new ways to approach and

challenge the decreased fertility in dairy cows came about. Early on examples of such scientific

fields included physiology and biochemistry, but more modern fields include various “omics”

fields, particularly culminating in the broad field of nutrigenomics. As the scientific body of

knowledge concerning physiology and biochemistry increased, the understanding of the

complexity of nutritional and dietary effects correspondingly grew, and insights into modulating

various aspects of physiology and metabolism through nutrition became apparent.

The endocrinology and physiology of growth mediated through the somatotropic and

gonadotropic axes became thoroughly understood by scientists, who then conducted research on

how nutrients affect the various interactions of these hormonal axes, such as dietary changes

altering ovarian follicular growth through changes in the somaotropic axes that influence how

follicular cells respond to hormones of the gonadotropic axes (Armstrong et al., 2002). Such

research evolved into the determination of specific metabolites that maximize reproductive


efficiency in cattle. In order to identify specific metabolites and understand their importance,

scientists needed to understand what metabolites are involved in the particular process being

analyzed, where the metabolites originated, and where the metabolites ended up.

Researchers primarily dealing with the issue of decreased fertility in dairy cows were

localized in the fields of genetics and reproduction until the concept of nutrition affecting

reproduction on the molecular level became common knowledge. The fields of nutrition,

genetics, and reproduction were merged into a systems biology approach that analyzed the

problem of decreased fertility in dairy cattle with a scope greater than using principles of

reproduction and genetic selection (McNamara, 2012). However, the trend towards merging of

scientific fields continued with the development of “omics” technologies, as such technologies

filled the needs of researchers to understand how nutrients become metabolites and the effects of

various metabolites in the body, specifically on fertility.

Various modern scientific fields, including genomics and metabolomics, are responsible

for mapping out genomes, metabolites, proteins, and other important molecular factors and

offered knowledge that nutritional researchers needed to continue progressing forward. Thus the

merging of the systems biology approach with other modern scientific fields occurred to create

the highly multifaceted field of nutrigenomics, which has the potential to analyze the problem of

decreased fertility in dairy cattle on a level much more in depth than ever before by looking at

how nutrients affect the somatotropic and gonadotropic axes and gene expression. The goal of

nutrigenomics is to improve the health of animals by analyzing their individual genetic code,

potentially allowing for variation between formulated diets to maximize fertility in dairy cows of

different ages or other subgroups. Differences between dairy cattle and beef cattle in terms of

nutrigenomics research will be vast, since dairy and beef cattle have been subjected to different


selective pressures and nutrigenomics research focuses on the very molecular level of

physiology.

Nutrigenomics is at the forefront of nutritional research of various companies, including

Alltech, with the intention of providing diets that take full advantage of an individual’s genetic

code to allow for maximized health. With the formation of nutrigenomics came a major step

towards the future of understanding the exact mechanisms of how the animal’s body functions in

response to nutrition, which has numerous applications in animal science. Currently, research

and review papers discuss how nutrigenomic technologies can be adapted to carry out accurate

and reliable studies on gene interactions, and future studies that incorporate nutrigenomics

technology will yield bits and pieces of information that will need to be compiled in a way

similar to how the human genome was mapped and collected as per the Human Genome Project

(Ghormade, 2011). Nutrigenomics is the clearly a move in the proper direction of figuring out

how to minimize fertility issues in dairy cows using a deeper understanding of nutrition and

genetics, instead of simple genetic selection for desired traits.

Conclusion

The emerging field of nutrigenomics developed along side scientists’ understanding of

the mechanisms of control in the animal’s body and also holds high prospects for solving a

variety of problems in the future. Nutrigenomics arose out of a systems biology approach put

forth by scientists who understood the need to integrate knowledge across different scientific

disciplines to solve modern problems. Molecular technology played a major role in the

development of nutrigenomics from the systems biology approach. Nutrigenomics, being

comprised of many molecular sciences, analyzes the genetic codes of individuals, allowing for a

high degree of variation in research between various dairy cows. Thus differences between


nutrigenomic studies for dairy and beef cattle are bound to be numerous due to the differences in

selective pressure for each group. One particular focus of nutrigenomics research opportunities

includes improving the decreased fertility observed in dairy cows as a result of targeted genetic

selection for milk production and quality traits; however, future studies will have to be

conducted and evaluated to determine how exactly to maximize the health and fertility of dairy

cows via nutrition, given the individual genetics of each cow.


Literature Cited

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Expression profiles of genes regulating dairy cow fertility: recent findings, ongoing

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nutrigenomics and dairy cattle repro final paper

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