Gene expression patterns in anterior pituitary associated with quantitative measure of oestrous behaviour in dairy cows

Intensive selection for high milk yield in dairy cows has raised production levels substantially but at the cost of reduced fertility, which manifests in different ways including reduced expression of oestrous behaviour. The genomic regulation of oestrous behaviour in bovines remains largely unknown. Here, we aimed to identify and study those genes that were associated with oestrous behaviour among genes expressed in the bovine anterior pituitary either at the start of oestrous cycle or at the mid-cycle (around day 12 of cycle), or regardless of the phase of cycle. Oestrous behaviour was recorded in each of 28 primiparous cows from 30 days in milk onwards till the day of their sacrifice (between 77 and 139 days in milk) and quantified as heat scores. An average heat score value was calculated for each cow from heat scores observed during consecutive oestrous cycles excluding the cycle on the day of sacrifice. A microarray experiment was designed to measure gene expression in the anterior pituitary of these cows, 14 of which were sacrificed at the start of oestrous cycle (day 0) and 14 around day 12 of cycle (day 12). Gene expression was modelled as a function of the orthogonally transformed average heat score values using a Bayesian hierarchical mixed model on data from day 0 cows alone (analysis 1), day 12 cows alone (analysis 2) and the combined data from day 0 and day 12 cows (analysis 3). Genes whose expression patterns showed significant linear or non-linear relationships with average heat scores were identified in all three analyses (177, 142 and 118 genes, respectively). Gene ontology terms enriched among genes identified in analysis 1 revealed processes associated with expression of oestrous behaviour whereas the terms enriched among genes identified in analysis 2 and 3 were general processes which may facilitate proper expression of oestrous behaviour at the subsequent oestrus. Studying these genes will help to improve our understanding of the genomic regulation of oestrous behaviour, ultimately leading to better management strategies and tools to improve or monitor reproductive performance in bovines

Gene expression patterns in four brain areas associate with quantitative measure of estrous behavior in dairy cows

<p>Abstract</p> <p>Background</p> <p>The decline noticed in several fertility traits of dairy cattle over the past few decades is of major concern. Understanding of the genomic factors underlying fertility, which could have potential applications to improve fertility, is very limited. Here, we aimed to identify and study those genes that associated with a key fertility trait namely estrous behavior, among genes expressed in four bovine brain areas (hippocampus, amygdala, dorsal hypothalamus and ventral hypothalamus), either at the start of estrous cycle, or at mid cycle, or regardless of the phase of cycle.</p> <p>Results</p> <p>An average heat score was calculated for each of 28 primiparous cows in which estrous behavior was recorded for at least two consecutive estrous cycles starting from 30 days post-partum. Gene expression was then measured in brain tissue samples collected from these cows, 14 of which were sacrificed at the start of estrus and 14 around mid cycle. For each brain area, gene expression was modeled as a function of the orthogonally transformed average heat score values using a Bayesian hierarchical mixed model. Genes whose expression patterns showed significant linear or quadratic relationships with heat scores were identified. These included genes expected to be related to estrous behavior as they influence states like socio-sexual behavior, anxiety, stress and feeding motivation (<it>OXT, AVP, POMC, MCHR1</it>), but also genes whose association with estrous behavior is novel and warrants further investigation.</p> <p>Conclusions</p> <p>Several genes were identified whose expression levels in the bovine brain associated with the level of expression of estrous behavior. The genes <it>OXT </it>and <it>AVP </it>play major roles in regulating estrous behavior in dairy cows. Genes related to neurotransmission and neuronal plasticity are also involved in estrous regulation, with several genes and processes expressed in mid-cycle probably contributing to proper expression of estrous behavior in the next estrus. Studying these genes and the processes they control improves our understanding of the genomic regulation of estrous behavior expression.</p

Genomic regulation of oestrous behaviour in dairy cows

Concurrent to the impressive improvement achieved over the last few decades for the trait of milk production in dairy cows was a steady decline in several fertility traits including oestrous behaviour (OB). An understanding of the genomic regulation of OB, which is currently lacking in dairy cows, will present new opportunities for managing this trait to help improve fertility. The research described in this thesis therefore aimed to achieve this understanding by studying gene expression in the bovine anterior pituitary (AP) and four brain areas (amygdala, hippocampus, dorsal hypothalamus and ventral hypothalamus) that are involved in regulating OB. A series of different analyses were performed that included model based association of gene expression with OB scores, gene co-expression and differential expression. In the association analyses, the identified genes included those previously not known to be related to OB associated processes as well as several genes expressed in mid-cycle that may have a function in the proper expression of OB at the next oestrus.Expected genesknown to be involved in OB associated processes like socio-sexual behaviour (e.g. OXT, AVP, GABRA6, HTR2A, DRD2), anxiety, stress and feeding motivation (e.g. POMC, MCHR1, TTR) were found along with genes associated with nervous system related processes (e.g.CHRM1, CHRM3, CHRNA5, CTLA4, IL1RL1, MARCO), suggesting a link between neuronal plasticity and OB. In the co-expression analyses, biological terms found common to several OB correlated consensus modules included general cellular processes like oxidative phosphorylation, ribosome and biosynthetic processes, indicating increased transcription and protein synthesis. These processes are primary events in the activation of neuronal cells and pathways involved in female reproductive behaviour and they precede the oestrogen driven expansion of dendrites and synapses. Hub genes within the OB correlated modules (e.g. NEFL, NDRG2, GAP43, THY1, TCF7L2 etc.) are strong candidates among genes regulating OB expression. Further, we showed the phenomenon of chromosomal regional regulation of transcription to exist in the bovine genome. To conclude, this study has revealed important new aspects of the genomic regulation of OB in dairy cows with the key findings presented within the framework of the GAPPS modules. The new knowledge could be used to optimize fertility of dairy cows by aiding to improve existing or to devise novel reproductive management tools like diagnostic tools to determine the reproductive health, energy and fertility status of the cow, oestrus detection tools and so on.</p