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The expression of estrous (sexually receptive) behavior (EB), a key fertility trait in dairy cows, has been declining over the past few decades both in intensity and duration. Improved knowledge of the genomic factors underlying EB, which is currently lacking, may lead to novel applications to enhance fertility. Our objective was to identify genes and biological processes shared among the bovine anterior pituitary (AP) and four brain areas that act together to regulate EB by investigating networks of coexpressed genes between these tissues. We used a systems biology approach called weighted gene coexpression network analysis for defining gene coexpression networks using gene expression data from the following tissues collected from 14 cows at estrus: AP, dorsal hypothalamus (DH), ventral hypothalamus (VH), amygdala (AM), and hippocampus (HC). Consensus modules of coexpressed genes were identified between the networks for the AM-DH, HC-DH, VH-DH, AP-DH, and AM-HC tissue pairs. The correlation between the module's eigengene (weighted average gene expression profile) and levels of EB exhibited by the experimental cows were tested. Estrous behavior-correlated modules were found enriched for gene ontology terms like glial cell development and regulation of neural projection development as well as for Kyoto Encyclopedia of Genes and Genomes pathway terms related to brain degenerative diseases. General cellular processes like oxidative phosphorylation and ribosome and biosynthetic processes were found enriched in several correlated modules, indicating increased transcription and protein synthesis. Stimulation of ribosomal RNA synthesis is known from rodent studies to be a primary event in the activation of neuronal cells and pathways involved in female reproductive behavior and this precedes the estrogen-driven expansion of dendrites and synapses. Similar processes also operate in cows to affect EB. Hub genes within EB-correlated modules (e.g. NEFL, NDRG2, GAP43, THY1, and TCF7L2, among others) are strong candidates among genes regulating EB expression. The study improved our understanding of the genomic regulation of EB in dairy cows by providing new insights into genes and biological processes shared among the bovine AP and brain areas acting together to regulate EB. The new knowledge could lead to the development of novel management strategies to monitor and improve reproductive performance in dairy cows (for example, biomarkers for estrus detection)., (Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The objective of this study was to describe fluctuations in leptin concentrations during late pregnancy and lactation and to investigate how those fluctuations are related to energy balance, milk yield, milk components, dry matter intake, live weight, first postpartum luteal activity, and first observed estrus during lactation. Live weight, dry matter intake, energy balance, and milk yield were measured weekly on 304 primiparous Holstein cows for the first 80 d of lactation. The first postpartum luteal activity was determined by measuring milk progesterone, and independently, first observed estrus. For measuring leptin concentrations from 30 d before until 80 d after calving, blood samples were taken at 2-wk intervals at a fixed time of the day after milking but before feeding. Leptin concentrations were high during pregnancy and declined to a nadir at parturition. It seems that leptin concentrations reflect the state of energy balance during lactation; plasma leptin concentrations were lower in cows with a mean negative energy balance during lactation. Those cows usually produced more milk, consumed less feed, and had a lower live weight compared with cows having a mean positive energy balance. The recovery of leptin concentrations from the leptin nadir at parturition seemed to depend on the extent and duration of the negative energy balance, thus probably on the amount of fat that was re-accumulated. Although there was lack of a relationship between leptin and first postpartum luteal activity, higher leptin concentrations associated with shorter intervals to first observed estrus might indicate a relationship between leptin and expression of estrus.

Leptin is a 16-kDa protein synthesized by adipose tissue and is involved in regulation of feed intake, energy balance, fertility, and immune functions. Since evidence of a genetic correlation between start of luteal activity and energy balance, milk yield, and live weights is present, we investigated the association of genetic differences in the bovine leptin gene with these traits. Between 1990 and 1997, a total of 613 Holstein-Friesian heifers of two genetic groups with known pedigree were followed from parturition until d 105 of lactation. During the first 15 wk of lactation live weight, feed intake, and milk yield were measured for 565 cows. The start of luteal activity was set at the first day with a progesterone concentration higher than 3 ng/ml. In addition to the interval between calving and start of luteal activity, analyses were performed for average milk yield, percentage fat, protein, and lactose in milk, dry matter intake, feed intake, energy balance, and live weight over the first 15 wk of lactation. All 613 cows were genotyped for two restricted fragment length polymorphisms and for the BM1500 microsatellite, all located at the leptin gene locus. Significances of the genotype effects were estimated using the approximated F-statistic provided by ASREML. Fixed effects were year-season, genetic group, and a quadratic polynomial for age at calving. Animal was fitted as a random effect including the additive relationship between animals to account for background genes. Firstly, each genotype effect was fitted in turn, and secondly the other restriction fragment length polymorphisms were fitted as a cofactor to take into account effects of linkage disequilibrium. Thirdly, sire x genotype interaction was investigated. Heifers with the RFLP1-AB genotype produce 1.32 kg/d more milk and consume 0.73 kg/d more food compared with the RFLP1-AA genotype. No effects were found for start of luteal activity. When linkage disequilibrium with the other markers was taken into account and DMI was included as fixed effect in the model a 0.96 kg/d higher milk yield was still found. Assuming that no pleiotropic effects on traits such as immunity and milk production in later lactations exist, future breeding programs favoring the RFLP1 B-allele can yield a higher milk production without negatively affecting energy balance and fertility. The prospects are good because in this study the frequency of the RFLP1 AB- and BB-genotypes were only 18.5 and 0.2%, respectively.