Central genomic regulation of the expression of oestrous behaviour in dairy cows: a review

The expression of oestrous behaviour in Holstein Friesian dairy cows has progressively decreased over the past 50 years. Reduced oestrus expression is one of the factors contributing to the current suboptimal reproductive efficiency in dairy farming. Variation between and within cows in the expression of oestrous behaviour is associated with variation in peripheral blood oestradiol concentrations during oestrus. In addition, there is evidence for a priming role of progesterone for the full display of oestrous behaviour. A higher rate of metabolic clearance of ovarian steroids could be one of the factors leading to lower peripheral blood concentrations of oestradiol and progesterone in high-producing dairy cows. Oestradiol acts on the brain by genomic, non-genomic and growth factor-dependent mechanisms. A firm base of understanding of the ovarian steroid-driven central genomic regulation of female sexual behaviour has been obtained from studies on rodents. These studies have resulted in the definition of five modules of oestradiol-activated genes in the brain, referred to as the GAPPS modules. In a recent series of studies, gene expression in the anterior pituitary and four brain areas (amygdala, hippocampus, dorsal hypothalamus and ventral hypothalamus) in oestrous and luteal phase cows, respectively, has been measured, and the relation with oestrous behaviour of these cows was analysed. These studies identified a number of genes of which the expression was associated with the intensity of oestrous behaviour. These genes could be grouped according to the GAPPS modules, suggesting close similarity of the regulation of oestrous behaviour in cows and female sexual behaviour in rodents. A better understanding of the central genomic regulation of the expression of oestrous behaviour in dairy cows may in due time contribute to improved (genomic) selection strategies for appropriate oestrus expression in high-producing dairy cows.     

Hormonal interelationships and physiological responses of lactating dairy cows to a shade management system in a subtropical environment

Lactating cows (n = 64) were assigned randomly to shade or no shade treatments for a continuous trial (20 wk) during summer of 1976. Respirations/min and rectal temperatures were higher for no shade cows. Dry matter forage intake was 9.7% higher for shade cows, whereas water intake was 19% greater for no shade cows. Milk yield and conception rates were higher for shade managed cows. Mean plasma corticoid concentrations were high throughout the entire estrous cycle in no shade compared to shade cows (13.04 > 8.72 ng/ml). No shade cows had higher progesterone and LH concentrations, and a lower estradiol to progesterone ratio during the cycle. Results indicated that endocrine changes were indicative of recurring estrous cycles in thermal stressed lactating dairy cows. However, alterations in water intake and thermoregulation of stressed cows were associated with decreased fertility and milk production, and changes in steroid concentrations that may reduce uterine blood flow.     

Screening for high fertility in high-producing dairy cows

A retrospective study involving 2756 pregnancies from two commercial dairy herds in northeastern Spain determined relationships between management, production and reproductive data, and high fertility (conception before 90 days in milk) in high-producing dairy cows. High fertility was registered in 989 (35.9%) cows. The following data were recorded for each animal: herd, repeated animal (cows included two or more times within the study in which data were obtained from different lactational periods), parity (primiparous versus multiparous), previous twinning, reproductive disorders following calving (retained placenta, primary metritis) and at postpartum gynecological examination (incomplete uterine involution, pyometra and ovarian cysts), days in milk at conception, previous estrous synchronization and season of calving and conception. In order to evaluate the possible effect of high production during the peak milk yield on subsequent fertility, daily milk production at Day 50 postpartum was also recorded and cows were classified as high (> or = 50 kg) and low (< 50 kg) producers. Logistic regression analysis indicated no significant effects of herd, repeated animal, previous twinning, reproductive disorders such as primary metritis, incomplete uterine involution, pyometra and ovarian cysts, previous estrous synchronization and season of calving and insemination. Based on the odds ratio, the likelihood of high fertility increased in high-producer cows by a factor of 6.8. High fertility was less likely for multiparous cows (by a factor of 0.35) and for cows suffering placenta retention (by a factor of 0.65). High fertile cows produced a mean of 49.5 kg milk at Day 50 postpartum, in contrast to that 43.2 kg milk of the remainder cows. These findings question the negative effect of high production on fertility. Our results indicated that high individual cow milk production can be positively related to high fertility.     

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.     

Review: Endocrine pathways to regulate calcium homeostasis around parturition and the prevention of hypocalcemia in periparturient dairy cows

Calcium homeostasis is crucial for the normal function of the organism. Parathyroid hormone, calcitriol and calcitonin play critical roles in the homeostatic regulation of calcium. Serotonin and prolactin have also been shown to be involved in the regulation of calcium homeostasis. In modern dairy cows, the endocrine pathways controlling calcium homeostasis during non-lactating and non-pregnant physiological states are unable to fully support the increased demand of calcium required for milk synthesis at the onset of lactation. This review describes different endocrine systems associated with the regulation of calcium homeostasis in mammalian species around parturition with special focus on dairy cows. Additionally, classic and novel strategies to reduce the incidence of hypocalcemia in parturient dairy cows are discussed.     

Effect of lameness on estrous behavior in crossbred cows

Lameness, a common disease in crossbred dairy cows, badly affects their fertility. To elucidate, if estrous behavior, comprising of duration and expression of certain estrous behavioral sign(s) (EBS), is involved, an estrous expression score system was applied to objectively compare estrous behavior during 27 and 58 estrous periods, respectively, in 17 normal and 37 lame cows kept in a group of 200 cows under loose housing system in tropical India. The cows were detected in estrus and were closely watched daily for 30 min at 0630, 1030, 1430 and 1830 h from the beginning to the end of estrus. The duration of estrus was similar in the normal and the lame cows (18.7+/-1.2 h versus 17.2+/-0.9 h) and almost similar EBS were shown by two types of cows, albeit with varying frequency. Standing to be mounted, the highest ranking EBS was shown by equal proportions of the cows in both the groups (76.4% versus 73.0%). A lower proportion of lame cows showed head side mounting (35% versus 53%; P<0.05). The frequency of standing to be mounted events was lower in the lame than in the normal cows (2.4+/-0.4 versus 8.0+/-2.5; P<0.05). The lame cows earned non-significantly lower than normal estrous behavior score (1100+/-179 versus 1610+/-357). Further, the presence of more than one cow simultaneously in estrus enhanced the estrous behavior score in the normal (406.4+/-63.0 for one cow in estrus versus 793.0+/-146.0 for three cows simultaneously in estrus; P<0.05), but not in the lame cows. Lameness appeared to have suppressed the playful behavior during estrus probably owing to pain related stress. It is concluded that mildly lame cows appear to have normal physiological estrus. However, some of the EBS remain subdued which prone them to remain undetected for timely breeding.     

A simple mathematical model of the bovine estrous cycle: follicle development and endocrine interactions

Bovine fertility is the subject of extensive research in animal sciences, especially because fertility of dairy cows has declined during the last decades. The regulation of estrus is controlled by the complex interplay of various organs and hormones. Mathematical modeling of the bovine estrous cycle could help in understanding the dynamics of this complex biological system. In this paper we present a mechanistic mathematical model of the bovine estrous cycle that includes the processes of follicle and corpus luteum development and the key hormones that interact to control these processes. The model generates successive estrous cycles of 21 days, with three waves of follicle growth per cycle. The model contains 12 differential equations and 54 parameters. Focus in this paper is on development of the model, but also some simulation results are presented, showing that a set of equations and parameters is obtained that describes the system consistent with empirical knowledge. Even though the majority of the mechanisms that are included in the model are based on relations that in the literature have only been described qualitatively (i.e. stimulation and inhibition), the output of the model is surprisingly well in line with empirical data. This model of the bovine estrous cycle could be used as a basis for more elaborate models with the ability to study effects of external manipulations and genetic differences.     

FABP5 is a critical regulator of methionine- and estrogen-induced SREBP-1c gene expression in bovine mammary epithelial cells

The intracellular fatty acid-binding proteins (FABPs) are a well-conserved family that function as lipid chaperones. Ongoing studies are focused on identification of the mechanistic complexity and vast biological diversity of different isoforms of FABPs. However, the molecular mechanism of FABP5 in the regulation of milk fat synthesis in the mammary gland of dairy cows is still largely unknown. Here, we report that FABP5 acts as a critical regulator of terol response element-binding protein-1c (SREBP-1c) gene expression induced by methionine (Met) and estrogen (E2) in bovine mammary epithelial cells (BMECs). We observed that the expression of FABP5 was markedly higher in dairy cow mammary tissue during the lactating period than the puberty period and the dry period. FABP5 is located in the cytoplasm, and Met and E2 significantly increase the protein levels of FABP5 in BMECs. Using gene function study approaches, we revealed that FABP5 positively regulates SREBP-1c gene expression and promotes milk fat synthesis. We confirmed that FABP5 is required for Met- and E2-induced SREBP-1c gene expression and milk fat synthesis. We further uncovered that fatty acids are needed for FABP5-mediated SREBP-1c gene expression. Thus, our study demonstrates that FABP5 is a critical regulator of Met- and E2-induced SREBP-1c gene expression leading to milk fat synthesis.     

Pre-parturition profile of steroids and prostaglandin in cows with or without foetal membrane retention

Retained foetal membranes in cattle is one of the most common complications associated to the reduction in milk yield and impaired fertility in dairy cattle. In order to determine some endocrine mechanisms controlling parturition and delivery of foetal membranes, plasma concentrations of steroids and prostanoids were determined in 20 healthy Holstein cows. Samples were taken within the interval of 5 days pre-parturition to 12h after calving. Progesterone (P4) levels were similar in cows with (PR) and without (NPR) placental retention. While the estradiol-17beta (E2) peak at parturition was lower in PR than in NPR cows, cortisol levels were greater in PR cows 12 and 24h pre-parturition. The Prostaglandin F2alpha metabolite (PGFM) levels were higher at parturition in NPR compared with the PR group, but 12h later, these levels in the PR group increased so that concentrations were greater as compared with NPR cows. The Prostaglandin E2 metabolite (PGEM), 24, 48 and 72 h pre-parturition, were higher in PR cows. However, the PGFM:PGEM ratio was greater in cows up NPR at all time when included, indicating the importance of higher levels of Prostaglandin F2alpha (PGF2alpha) than Prostaglandin E2 (PGE2) for normal placental delivery. In conclusion, placental retention was related to both estrogen and PGF2alpha deficiency, which may be a consequence of metabolic stress leading to PGE2 and maternal cortisol synthesis before parturition.     

食物限制对鼠类生理状况的影响

食物限制对鼠类生理特征产生明显影响。限食条件下,鼠类的能量消耗下降,能量需求降低,糖类、蛋白质和脂肪等物质的代谢过程及相应的酶活性改变,细胞免疫功能降低,神经内分泌发生变化,性成熟延迟,动情周期改变,动情行为受到抑制,生殖力下降,仔代的发育受到影响,性比发生变化。现就该领域近年来的研究进展做一综述,并提出一些新的思路。     

Genetic parameters for endocrine and traditional fertility traits,hyperketonemia and milk yield in dairy cattle

High-yielding cows may suffer from negative energy balance during early lactation, which can lead to ketosis and delayed ability of returning to cyclicity after calving. Fast recovery after calving is essential when breeding for improved fertility. Traditionally used fertility traits, such as the interval from calving to first insemination (CFI), have low heritabilities and are highly influenced by management decisions. Herd Navigator™ management program samples and analyses milk progesterone and β-hydroxybutyrate (BHB) automatically during milking. In this study, the genetic parameters of endocrine fertility traits (measured from milk progesterone) and hyperketonemia (measured from milk BHB) in early lactation were evaluated and compared with traditional fertility traits (CFI, interval from calving to the last insemination and interval from first to last insemination) and the milk yield in red dairy cattle herds in Finland. Data included observations from 14 farms from 2014 to 2017. Data were analyzed with linear animal models using DMU software and analyses were done for first parity cows. Heritability estimates for traditional fertility traits were low and varied between 0.03 and 0.07. Estimated heritabilities for endocrine fertility traits (interval from calving to the first heat (CFH) and commencement of luteal activity (C-LA)) were higher than for traditional fertility traits (0.19 to 0.33). Five slightly different hyperketonemia traits divided into two or three classes were studied. Linear model heritability estimates for hyperketonemia traits were low, however, when the threshold model was used for binary traits the estimates became slightly higher (0.07 to 0.15). Genetic correlation between CFH and C-LA for first parity cows was high (0.97) as expected since traits are quite similar. Moderate genetic correlations (0.47 to 0.52) were found between the endocrine fertility traits and early lactation milk yield. Results suggest that the data on endocrine fertility traits measured by automatic systems is a promising tool for improving fertility, specifically when more data is available. For hyperketonemia traits, dividing values into three classes instead of two seemed to work better. Based on the current study and previous studies, where higher heritabilities have been found for milk BHB traits than for clinical ketosis, milk BHB traits are a promising indicator trait for resistance to ketosis and should be studied more. It is important that this kind of data from automatic devices is made available to recording and breeding organizations in the future.     

Factors affecting the response to the specific treatment of several forms of clinical anestrus in high producing dairy cows

This study was designed to examine estrous response rates to the therapeutic treatment of clinical anestrus in high producing dairy cows and to identify the factors that could affect these rates. Cows with silent ovulation (Subestrus group), cystic ovarian disease (Cyst group) or ovarian hypofunction (OH group) were given specific treatment for their disorder. Data were derived from 1764 treatments in cows producing a mean of 45.4 kg of milk upon treatment including: 889 subestrous cows, 367 cystic cows and 508 cows with ovarian hypofunction. Cows showing estrus following treatment exhibited a similar pregnancy rate to cows attaining natural estrus used as reference: 33% (337/1006) and 35% (626/1796), respectively. No significant differences in pregnancy rates were observed among the Subestrus, Cyst and OH groups (34% (196/571), 34% (44/130), 32% (97/305), respectively. Based on the odds ratio, an estrous response for all groups was less likely to occur in cows that had suffered previous anestrus, compared to cows that were anestrous for the first time, whereas the likelihood of an estrous response increased in cows treated after 90 days in milk. Our results indicate that previous anestrus and a late stage of lactation can have a negative and positive effect, respectively, on the estrous response to the specific treatment of clinical anestrus shown by high producing dairy cows. Treatment targeted at each type of clinical anestrus can render similar pregnancy rates to those shown by cows in natural estrus.     

Prospects for improving reproductive performance through genetic selection

Prospects for improving female fertility in dairy cattle using genetic selection are reviewed. Today's high producing cows have shorter estrous cycles, fewer standing events, shorter duration of estrus, and more frequent multiple ovulations. Although high milk production is often implicated as the cause of impaired fertility, the impact of inadequate body condition appears to be greater, as the latter has a significant impact on probability of conception, rate of embryonic loss, and proportion of anestrous animals. Genetic improvement of female fertility can be achieved by indirect selection for longevity or body condition score, or by direct selection for traits such as daughter pregnancy rate. Most leading dairy countries have implemented genetic evaluation systems for female fertility in the past decade, but refinement of these systems to account for hormonal synchronization, differences in the voluntary waiting period, exposure to natural service bulls, and other confounding factors is warranted. Recent work has focused on the development of data collection and genetic evaluation systems that will allow selection of bulls that have daughters that are resistant to common health disorders, including mastitis, lameness, ketosis, displaced abomasum, and metritis. Such systems will allow selection of animals that can remain healthy and fertile while producing large quantities of milk.     

Relationship of declines in grain consumption and milk yield to estrus in dairy cattle

A retrospective study was done to determine if a reduction in daily grain consumption or decline in daily milk yield were accurate indicators of estrus in 25 Holstein cows. A computer automatically identified all cows that left more than 10% of their daily grain allocation in the feed stall or that gave less than 85% of their most current 7-d daily average milk yeild. By retrospectively analyzing breeding records, grain refusal and milk declines were identified as either occurring in conjunction with estrus or nonestrus. Declines in grain consumption and milk yield were frequently associated with estrus, but many cows in estrus did not exhibit such declines. While such declines hold promise as estrous detection aids, it was concluded that refusals of daily grain allocation or declines in daily milk yield were not sufficiently accurate to supplant other methods of estrous detection in dairy cattle.     

The impact of controlled nutrition during the dry period on dairy cow health, fertility and performance

Average dairy herd fertility is declining, with more serves per successful conception, extended calving intervals and increased culling due to failure to rebreed, all adding significant costs to milk production. Genetics, management and nutrition have all contributed to this decline in fertility; the paper focuses primarily on nutritional issues. The extent of body condition loss after calving and its possible impact on fertility is considered, with evidence that this phenomenon is common in many herds irrespective of average milk yields. Body tissue mobilisation after calving increases the flux of non-esterified fatty acids to the liver and pathways of fatty acid metabolism are considered. Particular attention is given to the effects of high plasma non-esterified fatty acid levels on fat accumulation in liver cells and possible impacts on nitrogen and glucose metabolism. Current nutritional practices with early lactation cows which aim to stimulate milk yield and peak milk production but have been shown to exacerbate body condition loss, are reviewed. The paper also considers cow health issues during the peri-parturient period and how these may affect milk yield and fertility. It is concluded that current feeding practices for dry cows, with the provision of increasing amounts of the lactation ration during the Close-up period to accustom the rumen microbes and offset the expected reduction in feed intake as pregnancy reaches term, have largely failed to overcome peri-parturient health problems, excessive body condition loss after calving or declining fertility. From an examination of the energy and protein requirements of dry cows, it is suggested that current Close-up feeding practices can lead to luxury intakes of nutrients that can increase fat deposition in the viscera and the liver. Under such conditions, metabolism of nutrients by the cow may be compromised. In contrast, limited feeding throughout the whole dry period has been shown to prevent many of the problems which can affect peri-parturient cows. A new feeding strategy based on a low energy: high fibre ration (9 MJ metabolisable energy and 130 g crude protein/kg ration dry matter) containing high levels of chopped straw and offered ad libitum as a total mixed ration throughout the whole dry period is proposed. The performance of 32 dairy farms in France where this strategy has been adopted for at least 3 years is provided, with positive outcomes now being obtained by UK and Irish dairy farmers. Independent US research evidence has confirmed some of these benefits whilst limited data on cow fertility is presented. It is hypothesised that luxury feeding during the dry period can cause cows to become insulin resistant leading to an increased risk of type II diabetes. Such cows are likely to have poorer fertility whilst possible mechanisms which increase the risk of peri-parturient health problems are discussed. Further research to understand the mechanisms of these effects is required and is currently ongoing. However the magnitude of the effects noted on an increasing number of dairy farms suggests this approach to feeding the dry cow is capable of bringing real benefits to many dairy herds in terms of fewer health problems, reduced body condition loss and improved fertility.     

Relationship among estradiol, cortisol and intensity of estrous behavior in dairy cattle

Economic profitability of a dairy farm is based, in part, on the calving interval of the cows. The optimal interval is 365 d. To achieve this, the cow needs to be pregnant within 85 d post partum. The first and most problematic step in this process is the determination of the optimal time for insemination, which is based on estrous behavior. The expression of estrous behavior, however, is at a low level in modem dairy herds, resulting in low detection rates and longer calving intervals. In the present study, a point scale was used to monitor postpartum, nonpregnant cows for estrous symptoms. Frequent blood samples were taken around estrus, and the cows were fit with pedometers to measure their activity. Correlations between the occurrence of symptoms of estrus and levels of estradiol and cortisol were then analyzed. Standing heat, the standard symptom of estrus, was observed in only 53% of the cows. A high correlation of 0.7 was found between estradiol concentration and estrous behavior. This was empasized by the fact that the estradiol level reached its highest level of 7.76 + 2.39 (SD) pg/mL at the same time as the highest behavior score. The highest pedometer readout lagged 8 h behind this moment. Cortisol levels did not exceed the physiological levels in rest situations but showed an increase at the time estrous behavior was at its maximum. The present study showed that standing heat is not the primary symptom for detecting estrus in cows. Pedometers are a useful aid but they have to be read several times a day. The high correlation between the visual symptoms of estrus and estradiol concentrations indicates that visual estrus detection is an efficient, reliable way to determine the right time for insemination.