One Health: Circadian Medicine Benefits Both Non-human Animals and Humans Alike.

Circadian biology's impact on human physical health and its role in disease development and progression is widely recognized. The forefront of circadian rhythm research now focuses on translational applications to clinical medicine, aiming to enhance disease diagnosis, prognosis, and treatment responses. However, the field of circadian medicine has predominantly concentrated on human healthcare, neglecting its potential for transformative applications in veterinary medicine, thereby overlooking opportunities to improve non-human animal health and welfare. This review consists of three main sections. The first section focuses on the translational potential of circadian medicine into current industry practices of agricultural animals, with a particular emphasis on horses, broiler chickens, and laying hens. The second section delves into the potential applications of circadian medicine in small animal veterinary care, primarily focusing on our companion animals, namely dogs and cats. The final section explores emerging frontiers in circadian medicine, encompassing aquaculture, veterinary hospital care, and non-human animal welfare and concludes with the integration of One Health principles. In summary, circadian medicine represents a highly promising field of medicine that holds the potential to significantly enhance the clinical care and overall health of all animals, extending its impact beyond human healthcare.

Impact of growth trajectory on sexual maturation in layer chickens.

Recent studies showed that apart from photostimulation, metabolic triggers may independently activate sexual maturation and egg production in chickens. However, the origin, mode of action, and specific target(s) of this metabolic control remain unknown. Beyond body weight (BW), we hypothesize that body composition (BC) and associated specific metabolic signals are involved. Thus, this study was conducted to determine the BW and BC thresholds triggering spontaneous sexual maturation in layer pullets under different growth trajectories. Day-old Lohman LSL lite and Lohman brown lite chicks (n = 210 each) raised in brooding cages under ad libitum (AL) feeding until 8 weeks of age were randomly allocated into individual cages and assigned to one of 3 experimental growth profiles; AL, breeder's target (T), restricted 20% below target (R), (n = 70 birds/profile/strain). Birds had free access to water throughout the trial. All hens were maintained on 10 h of light (10 lux) throughout the rest of the study. Blood and tissue samples were collected throughout the study to measure plasma estradiol (E2) concentrations and organ weights, respectively. Furthermore, carcasses were subjected to Dual-energy X-ray absorptiometry (DEXA) analyses. All analyses were completed with SAS using the MIXED procedure. Results show that R treatment slowed (p < 0.001) growth, delayed age at first egg (FE) and egg production (p < 0.001) and resulted in lower BW at FE (p < 0.001), lower ovary weight and number of follicles (p < 0.001) compared to AL in both strains, whereas, the strain significantly impacted body weight (p < 0.0001), ovary weight (p < 0.001), BW at FE (p < 0.001), age at FE (p < 0.001), egg production (p < 0.0001), E2 (p < 0.0001) and body composition (p < 0.05). For DEXA, AL feeding (p < 0.001) increased fat deposition compared to R. Furthermore, there was a positive correlation between plasma E2 and bone mineral content (p < 0.01) and bone mineral density (p < 0.01). In conclusion, feed allocation impacted growth and BC in a strain dependent manner which resulted in differing age at sexual maturation and egg production. Furthermore, a body fat threshold between 10% to 15% appears to be required for the occurrence of spontaneously sexual maturation in laying hens.

Continuous exposure to red light induces photorefractoriness in broiler breeder pullets.

The management of body weight (BW) in broiler breeder pullets is critical to offset the negative correlation between their growth potential and reproductive success. Therefore, a precision feeding system was developed to allocate feed individually based on real-time BW in more frequent, smaller portions. However, this system requires access beyond the 8 h daylength of the rearing period. Since green and red spectra have been shown to stimulate growth and sexual maturation, respectively, this study aimed to evaluate the impact of continuous supplemental illumination of feeders with monochromatic wavelengths on sexual maturation. Furthermore, the best combination of supplemental and daytime lighting for optimizing the pullet-to-hen transition period was investigated. This study contained a 2 × 4 × 2 factorial arrangement, with 2 daytime lights (dtRED and dtGREEN; n = 2 rooms), 4 supplemental lights (sBLUE, sGREEN, sRED, and sCON; n = 12 pens), and 2 supplemental intensities (High and Low). At 3 wk of age (woa), 480 female Ross 708 chicks were randomly distributed across treatments (n = 10/pen). All birds were feed restricted per management guidelines and maintained under 8 h of dtRED or dtGREEN. Birds were photostimulated at 20 woa with 14L:10D. All birds were weighed weekly, with age at first egg (AFE) and production rate calculated weekly per pen. Birds under sRED were heavier than all other treatments from 27 woa to the end of the study (P < 0.001; 30 woa), resulting in hens that were over 400-g heavier. This resulted from a delayed AFE and lower production rate under sRED, with higher intensity further hindering reproductive performance (P < 0.001). Interestingly, despite the inhibitory effect of continuous red lighting (sRED) on reproduction, dtRED resulted in a 3.15% higher rate of lay than dtGREEN. Therefore, this study suggests that while red light remains superior at stimulating reproduction, continuous red supplemental lighting results in photorefractoriness. Thus, we recommend green light in PF systems.

Turkey hen sperm storage tubule transcriptome response to artificial insemination and the presence of semen.

Introduction: Sperm storage within the uterovaginal junction (UVJ) of avian species occurs in specialized structures termed sperm storage tubules (SSTs) and allows for prolonged storage of semen, though the molecular mechanisms involved in semen preservation are not well understood. Little work has been done examining how function of the SSTs is impacted by insemination and by semen present in the SSTs. Methods: Transcriptome analysis was performed on isolated SSTs from turkey hens receiving no insemination (control), sham-insemination, or semen-insemination at three timepoints (D1, D30, and D90 post-insemination). Bioinformatic and functional annotation analyses were performed using CLC Genomics Workbench, Database for Annotation, Visualization, and Integrated Discovery (DAVID), and Ingenuity Pathway Analysis (IPA). Pairwise comparisons and k-medoids cluster analysis were utilized to decipher differential expression profiles in the treatment groups. Results: The SST transcriptome of the semen inseminated group exhibited the greatest differences within the group, with differences detectable for up to 90 days post insemination, while control and sham-inseminated groups were more similar. In the semen-inseminated samples, upregulation of pathways relating to classical and non-classical reproductive signaling, cytoskeletal remodeling, physiological parameters of the local UVJ environment, and cellular metabolism was observed. In the sham-inseminated samples, upregulation of immune pathways and non-reproductive endocrine hormones was observed. Discussion: This work provides insights into the molecular level changes of the SST in response to insemination as well as to the presence of semen. Results from this study may have direct implications on fertility rates as well as potential strategies for avian semen cryopreservation protocols.

The Diverse Roles of 17ß-Estradiol in Non-Gonadal Tissues and Its Consequential Impact on Reproduction in Laying and Broiler Breeder Hens.

Estradiol-17ß (E2) has long been studied as the primary estrogen involved in sexual maturation of hens. Due to the oviparous nature of avian species, ovarian production of E2 has been indicated as the key steroid responsible for activating the formation of the eggshell and internal egg components in hens. This involves the integration and coordination between ovarian follicular development, liver metabolism and bone physiology to produce the follicle, yolk and albumen, and shell, respectively. However, the ability of E2 to be synthesized by non-gonadal tissues such as the skin, heart, muscle, liver, brain, adipose tissue, pancreas, and adrenal glands demonstrates the capability of this hormone to influence a variety of physiological processes. Thus, in this review, we intend to re-establish the role of E2 within these tissues and identify direct and indirect integration between the control of reproduction, metabolism, and bone physiology. Specifically, the sources of E2 and its activity in these tissues via the estrogen receptors (ERα, ERß, GPR30) is described. This is followed by an update on the role of E2 during sexual differentiation of the embryo and maturation of the hen. We then also consider the implications of the recent discovery of additional E2 elevations during an extended laying cycle. Next, the specific roles of E2 in yolk formation and skeletal development are outlined. Finally, the consequences of altered E2 production in mature hens and the associated disorders are discussed. While these areas of study have been previously independently considered, this comprehensive review intends to highlight the critical roles played by E2 to alter and coordinate physiological processes in preparation for the laying cycle.

Bone and eggshell quality throughout an extended laying cycle in three strains of layers spanning 50 years of selection.

Decades of intensive genetic selection in commercial layers has resulted in earlier maturation, while sustaining high production rates to 100 wks of age (woa). To support eggshell formation while maintaining a healthy skeletal frame, substantial adaptations of calcium metabolism in the hen are necessary. Thus, skeletal growth, bone density, and egg quality were compared in 3 strains of layers, with the Lohmann LSL-lite as the current commercial strain, the heritage Shaver white leghorn as the mid-2000s strain, and the white-leghorn derived Smoky Joes as the non-selected 1960s strain. Tibia and Femur (n = 4/strain) were collected at 12, 17, 20, 25, 45, 60, 75, and 100 woa. Bones were measured and weighed, with bone mineral density assessed within medullary (mBMD) and cortical (cBMD) regions of the tibia using micro-Computed Tomography. Egg analyses including weight, eggshell thickness (EST) and eggshell breaking strength (EBS), were conducted throughout lay. Blood samples were collected to measure plasma calcium immediately prior to lay (18 woa) and periodically throughout the laying cycle. Femur and tibia weight, or size, did not increase beyond 12 woa, indicating that all hens reached maximum skeletal size by this time. An interaction (P = 0.005) was observed between strain and tibia mBMD, as all three strains demonstrated an accumulation of medullary bone from 12 to 100 woa. Regarding egg weight, while Lohmann hen eggs displayed the highest quality at 26 woa, an elevation in egg weight in Lohmann and Shaver hens (P < 0.001) resulted in a decline in EST and EBS over time (P < 0.01). Yet, at 100 woa, no strain differed in EST or EBS, despite larger variations in cumulative egg numbers (P < 0.001). Plasma calcium levels were significantly elevated between the immature state and peak of lay but remained unchanged throughout lay in all strains. In conclusion, our results show that although genetic selection of layer hens resulted in tremendous improvement in productivity, no detrimental effects on cBMD or mBMD were observed throughout an extended laying period up to 100 woa.

Changes in the Control of the Hypothalamic-Pituitary Gonadal Axis Across Three Differentially Selected Strains of Laying Hens (Gallus gallus domesticus).

Genetic selection for earlier sexual maturation and extended production cycles in laying hens has significantly improved reproductive efficiency. While limited emphasis has been placed on the underlying physiological changes, we hypothesize that modifications in the control of the hypothalamic-pituitary gonadal (HPG) axis have occurred. Thus, three strains of White leghorn derivatives were followed from hatch to 100 weeks of age (woa), including Lohmann LSL-lite (n = 120) as current commercial hens, heritage Shaver White leghorns (n = 100) as 2000s commercial equivalents, and Smoky Joe hens (n = 68) as 1960s commercial equivalents. Body weight (BW) and egg production were monitored, and blood samples were collected throughout to monitor estradiol (E2) concentrations. Tissue samples were collected at 12, 17, 20, 25, 45, 60, 75, and 100 woa to capture changes in mRNA levels of key genes involved in the HPG axis and monitor ovarian follicular pools. All hens, regardless of strain, age or photoperiod laid their first egg within a 64-gram BW window and, as E2 levels increased prior to photostimulation (PS) in Lohmann and Shaver hens, a metabolic trigger likely induced sexual maturation. However, increased levels of Opsin 5 (OPN5) were observed during the maturation period. Although an elevation in gonadotrophin-releasing hormone I (GnRH-I) mRNA levels was associated with early maturation, no changes in gonadotrophin-inhibitory hormone (GnIH) mRNA levels were observed. Nonetheless, a significant shift in pituitary sensitivity to GnRH was associated with maturation. Throughout the trial, Lohmann, Shaver, and Smoky Joe hens laid 515, 417, and 257 eggs, respectively (p < 0.0001). Results show that the extended laying persistency in Lohmann hens was supported by sustained pituitary sensitivity to GnRH-I, recurrent elevations in follicle-stimulating hormone (FSH) mRNA levels, and five cyclical elevations in E2 levels. This was also associated with a consistently higher pool of small white ovarian follicles. In summary, our results demonstrate first that, regardless of photoperiodic cues, meeting a specific narrow body weight threshold is sufficient to initiate sexual maturation in Leghorn chicken derivatives. Furthermore, recurrent increases in E2 and FSH may be the key to sustain extended laying period, allowing modern layers to double their reproductive capacity compared to their 1960s-counterparts.

Gonadotropin Inhibitory Hormone and Its Receptor: Potential Key to the Integration and Coordination of Metabolic Status and Reproduction.

Since its discovery as a novel gonadotropin inhibitory peptide in 2000, the central and peripheral roles played by gonadotropin-inhibiting hormone (GnIH) have been significantly expanded. This is highlighted by the wide distribution of its receptor (GnIH-R) within the brain and throughout multiple peripheral organs and tissues. Furthermore, as GnIH is part of the wider RF-amide peptides family, many orthologues have been characterized across vertebrate species, and due to the promiscuity between ligands and receptors within this family, confusion over the nomenclature and function has arisen. In this review, we intend to first clarify the nomenclature, prevalence, and distribution of the GnIH-Rs, and by reviewing specific localization and ligand availability, we propose an integrative role for GnIH in the coordination of reproductive and metabolic processes. Specifically, we propose that GnIH participates in the central regulation of feed intake while modulating the impact of thyroid hormones and the stress axis to allow active reproduction to proceed depending on the availability of resources. Furthermore, beyond the central nervous system, we also propose a peripheral role for GnIH in the control of glucose and lipid metabolism at the level of the liver, pancreas, and adipose tissue. Taken together, evidence from the literature strongly suggests that, in fact, the inhibitory effect of GnIH on the reproductive axis is based on the integration of environmental cues and internal metabolic status.

Should I Lay or Should I Grow: Photoperiodic Versus Metabolic Cues in Chickens.

While photoperiod has been generally accepted as the primary if not the exclusive cue to stimulate reproduction in photoperiodic breeders such as the laying hen, current knowledge suggests that metabolism, and/or body composition can also play an influential role to control the hypothalamic-pituitary gonadal (HPG)-axis. This review thus intends to first describe how photoperiodic and metabolic cues can impact the HPG axis, then explore and propose potential common pathways and mechanisms through which both cues could be integrated. Photostimulation refers to a perceived increase in day-length resulting in the stimulation of the HPG. While photoreceptors are present in the retina of the eye and the pineal gland, it is the deep brain photoreceptors (DBPs) located in the hypothalamus that have been identified as the potential mediators of photostimulation, including melanopsin (OPN4), neuropsin (OPN5), and vertebrate-ancient opsin (VA-Opsin). Here, we present the current state of knowledge surrounding these DBPs, along with their individual and relative importance and, their possible downstream mechanisms of action to initiate the activation of the HPG axis. On the metabolic side, specific attention is placed on the hypothalamic integration of appetite control with the stimulatory (Gonadotropin Releasing Hormone; GnRH) and inhibitory (Gonadotropin Inhibitory Hormone; GnIH) neuropeptides involved in the control of the HPG axis. Specifically, the impact of orexigenic peptides agouti-related peptide (AgRP), and neuropeptide Y (NPY), as well as the anorexigenic peptides pro-opiomelanocortin (POMC), and cocaine-and amphetamine regulated transcript (CART) is reviewed. Furthermore, beyond hypothalamic control, several metabolic factors involved in the control of body weight and composition are also presented as possible modulators of reproduction at all three levels of the HPG axis. These include peroxisome proliferator-activated receptor gamma (PPAR-γ) for its impact in liver metabolism during the switch from growth to reproduction, adiponectin as a potential modulator of ovarian development and follicular maturation, as well as growth hormone (GH), and leptin (LEP).