Celebrating a milestone and looking at the future of Theriogenology.

In 2024, Theriogenology turned 50! The purpose of this special issue is to emphasize the pivotal role of reproduction and fertility in improving the efficacy and sustainability of animal production in a range of environments (different production systems, different climates, or different consumer-related expectations). A first series of articles summarizes the possibilities and constraints linked to embryo production (in vivo and in vitro) as well as the potential of novel embryo technologies. A second series provides an overview of the future of production and reproduction for the next 20 years in different species and geographical areas.

MRI findings in six dogs with ependymoma of the brain and spinal cord.

There are few published descriptions of the MRI appearance of canine intracranial or spinal cord ependymoma. In this multicenter, retrospective, secondary analysis, case series study, three veterinary radiologists independently reviewed and recorded imaging characteristics of MRI studies in six dogs with histopathologically confirmed ependymoma (three intracranial and three spinal cord cases). A consensus was reached when there was disagreement on specific features.

Glycemia and Insulin Secretion in Cystic Fibrosis Two Years After Elexacaftor/Tezacaftor/Ivacaftor: PROMISE-ENDO.

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) is a highly effective therapy that improves lung disease in people with cystic fibrosis (pwCF), but its effect on glucose tolerance and insulin secretion is unclear.

Methods: PROMISE is a multicenter prospective, observational study of ETI in pwCF ≥12 years and at least one F508del allele. The PROMISE Endocrine sub-study (PROMISE-ENDO) enrolled participants at 10 CF Centers where hemoglobin A1c (HbA1c) was collected and 3-hour oral glucose tolerance tests (OGTT) conducted to examine glucose tolerance, glucose excursions, insulin secretory rates (deconvolution of C-peptide) and sensitivity (oral minimal model) prior to ETI and 12-18 months (mos) and 24-30 mos following ETI initiation.

An erythroid-specific lentiviral vector improves anemia and iron metabolism in a new model of XLSA.

X-linked sideroblastic anemia (XLSA) is a congenital anemia caused by mutations in ALAS2, a gene responsible for heme synthesis. Treatments are limited to pyridoxine supplements and blood transfusions, offering no definitive cure except for allogeneic hematopoietic stem cell transplantation, only accessible to a subset of patients. The absence of a suitable animal model has hindered the development of gene therapy research for this disease.

TLR priming licenses NAIP inflammasome activation by immunoevasive ligands.

NLR family, apoptosis inhibitory proteins (NAIPs) detect bacterial flagellin and structurally related components of bacterial type III secretion systems (T3SS), and recruit NLR family CARD domain containing protein 4 (NLRC4) and caspase-1 into an inflammasome complex that induces pyroptosis. NAIP/NLRC4 inflammasome assembly is initiated by the binding of a single NAIP to its cognate ligand, but a subset of bacterial flagellins or T3SS structural proteins are thought to evade NAIP/NLRC4 inflammasome sensing by not binding to their cognate NAIPs. Unlike other inflammasome components such as NLRP3, AIM2, or some NAIPs, NLRC4 is constitutively present in resting macrophages and not known to be induced by inflammatory signals.

Place conditioning as evaluation of affective valence in piglets.

The emotional valence of animals is challenging to assess, despite being a key component of welfare. In this study, we attempted to assess emotional valence through memory in 1- and 3-week-old piglets. It was hypothesized that piglets would spend less time in a pen where they experienced a negative event (castration) and more time in a pen where they experienced a positive event (enrichment).

Effect of refreezing extender on stallion sperm quality and embryo production after intracytoplasmic sperm injection.

Intracytoplasmic sperm injection (ICSI) is a valuable assisted reproduction technology in clinical practice, especially when semen availability is limited. Since the number of sperm required per ICSI cycle is much less than the number of sperm available in a standard straw of frozen semen, refreezing semen at lower sperm concentrations could yield multiple straws for ICSI use. However, there is little data on the effect of sperm refreezing on ICSI outcomes, especially on the effect of extender used for refreezing.

Quality assurance applied to semen analysis.

Artificial insemination is an important biotechnology employed in livestock production. Production of semen products requires analysis of sperm concentration, motility and morphology. Although adequate analytical procedures are essential to ensure product quality, several multicenter studies have reported large variations in semen analysis results within and across laboratories.

Seasons of death: patterns of predation on wild lemurs and other fauna by endemic and introduced predators.

Introduced species can negatively impact endemic flora and fauna. Studies have primarily utilized camera trap observations and occupancy modelling to better clarify the presence/absence and temporal overlap of endemic and exotic predators. Longitudinal data from field research sites are important as they can provide a finer understanding of predator dynamics and their effects on endemic species.

Pain pathophysiology and pharmacology of cattle: how improved understanding can enhance pain prevention, mitigation, and welfare.

Globally, humans rely on cattle for food production; however, there is rising societal concern surrounding the welfare of farm animals. From a young age, cattle raised for dairy and beef production experience pain caused by routine management procedures and common disease conditions. The fundamental mechanisms, nociceptive pathways, and central nervous system structures required for pain perception are highly conserved among mammalian species.

Money, Mentorship, and Misinformation: Barriers and Facilitators to Veterinarians' Pursuit of Postdoctoral Training in Laboratory Animal Medicine.

Since 2015, it has become progressively more difficult for programs to recruit residents in laboratory animal medicine (LAM). Veterinarians are a necessary part of animal research, and having a shortage in veterinarians trained to work in this field has the potential to negatively impact research progress as well as animal welfare. With a goal to increase recruitment, we performed this study to better understand the barriers and facilitators that veterinarians experience when navigating the decision to pursue postdoctoral training in LAM.

TRIP13 localizes to synapsed chromosomes and functions as a dosage-sensitive regulator of meiosis.

Meiotic progression requires coordinated assembly and disassembly of protein complexes involved in chromosome synapsis and meiotic recombination. Mouse TRIP13 and its ortholog Pch2 are instrumental in remodeling HORMA domain proteins. HORMAD proteins are associated with unsynapsed chromosome axes but depleted from the synaptonemal complex (SC) of synapsed homologs.

Blockade of IKK signaling induces RIPK1-independent apoptosis in human macrophages.

Regulated cell death in response to microbial infection plays an important role in immune defense and is triggered by pathogen disruption of essential cellular pathways. Gram-negative bacterial pathogens in the Yersinia genus disrupt NF-κB signaling via translocated effectors injected by a type III secretion system, thereby preventing induction of cytokine production and antimicrobial defense. In murine models of infection, Yersinia blockade of NF-κB signaling triggers cell-extrinsic apoptosis through Receptor Interacting Serine-Threonine Protein Kinase 1 (RIPK1) and caspase-8, which is required for bacterial clearance and host survival.

Kinetics and Retention of Polystyrenesulfonate for Proteoglycan Replacement in Cartilage.

Tissue hydration provides articular cartilage with dynamic viscoelastic properties. Early stage osteoarthritis (OA) is marked by loss of proteoglycans and glycosaminoglycans (GAG), lowering fixed charge density, and impairing tissue osmotic function. The most common GAG replacement, chondroitin sulfate (CS), has failed to show effectiveness.

Insulin sensitivity and insulin secretion in adults with Friedreich's Ataxia: the role of skeletal muscle.

Introduction: Friedreich's Ataxia (FRDA) is a multi-system disorder caused by frataxin deficiency. FRDA-related diabetes mellitus (DM) is common. Frataxin supports skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity, a mediator of insulin sensitivity.

Insulin sensitivity, disposition index and insulin clearance in cystic fibrosis: a cross-sectional study.

Aims/hypothesis: The aim of this study was to investigate insulin secretion, insulin sensitivity, disposition index and insulin clearance by glucose tolerance status in individuals with cystic fibrosis (CF) and exocrine pancreatic insufficiency.

Methods: In a cross-sectional study, we conducted an extended (ten samples) OGTT in individuals with pancreatic-insufficient CF (PI-CF). Participants were divided into normal glucose tolerance (NGT), early glucose intolerance (EGI), impaired glucose tolerance (IGT) and CF-related diabetes (CFRD) groups.

Distinct sequential death complexes regulate pyroptosis and IL-1β release in response to blockade of immune signaling.

Pathogen infection of host cells triggers an inflammatory cell death termed pyroptosis via activation of inflammatory caspases. However, blockade of immune signaling kinases by the virulence factor YopJ triggers cell death involving both apoptotic caspase-8 and pyroptotic caspase-1. While caspase-1 is normally activated within inflammasomes, -induced caspase-1 activation is independent of known inflammasome components.

Single-cell multi-omic and spatial profiling of human kidneys implicates the fibrotic microenvironment in kidney disease progression.

Kidneys are intricate three-dimensional structures in the body, yet the spatial and molecular principles of kidney health and disease remain inadequately understood. We generated high-quality datasets for 81 samples, including single-cell, single-nuclear, spot-level (Visium) and single-cell resolution (CosMx) spatial-RNA expression and single-nuclear open chromatin, capturing cells from healthy, diabetic and hypertensive diseased human kidneys. Combining these data, we identify cell types and map them to their locations within the tissue.

Multimodal distribution and its impact on the accurate assessment of spermatozoa morphological data: Lessons from machine learning.

Objective assessment of sperm morphology is an essential component for assessing ejaculate quality. Due to economic limitations, investigators often divert to conducting observational studies instead of experimental ones, which provide the strongest statistical power, yielding more heterogeneous data regardless of the number of data sources (barns/farms). Using such data inevitably leads to higher variances of estimates, which negatively impacts the statistical power of a study.

Accumulation of alkyl-lysophosphatidylcholines in Niemann-Pick disease type C1.

Lysosomal function is impaired in Niemann-Pick disease type C1 (NPC1), a rare and inherited neurodegenerative disorder, resulting in late endosomal/lysosomal accumulation of unesterified cholesterol. The precise pathogenic mechanism of NPC1 remains incompletely understood. In this study, we employed metabolomics to uncover secondary accumulated substances in NPC1.

Loss of Lymphatic IKKα Disrupts Lung Immune Homeostasis, Drives BALT Formation, and Protects against Influenza.

IκB kinase (IKK)α controls noncanonical NF-κB signaling required for lymphoid organ development. We showed previously that lymph node formation is ablated in IkkαLyve-1 mice constitutively lacking IKKα in lymphatic endothelial cells (LECs). We now reveal that loss of IKKα in LECs leads to the formation of BALT in the lung.