1. 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

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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

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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

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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

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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

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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

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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

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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

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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

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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.

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Literature Cited
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Beerda, B., J. Wyszynska-Koko, M. F. W. te Pas, A. A. C. de Wit, and R. F. Veerkamp. 2008.
Expression profiles of genes regulating dairy cow fertility: recent findings, ongoing
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Chagas, L. M., J. J. Bass, D. Blache, C. R. Burke, J. K. Kay, D. R. Lindsay, M. C. Lucy, G. B.
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Dawson, K. A. 2006. Nutrigenomics: Feeding the genes for improved fertility. Animal
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Fenech, M., A. El-Sohemy, L. Cahill, L. R. Ferguson, T. C. French, E. S. Tai, J. Milner, W. Koh,
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Ghormade, V., A. Khare, and R. P. S. Baghel. 2011. Nutrigenomics and its applications in
animal science. Veterinary Research Forum 2:147-155.

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Kore, K. B., A. K. Pathak, and Y. P. Gadekar. 2008. Nutrigenomics: emerging face of
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