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PloS One 2024Feeding high-gain diets and an inadequate energy and protein ratio during pre-puberty may lead to impaired growth and mammary gland development of heifers. Thus,...
Feeding high-gain diets and an inadequate energy and protein ratio during pre-puberty may lead to impaired growth and mammary gland development of heifers. Thus, frequent application of bovine somatotropin (bST) may prevent future losses in productivity, improve mammary development and animal performance. We aimed to evaluate the effects of bST on digestibility, performance, blood metabolites, mammary gland development, and carcass composition of high-performance prepubertal Holstein × Gyr heifers. Thirty-four Holstein × Gyr heifers with an average initial body weight of 218 ± 49 kg and 14 ± 4 months of age were submitted to an 84-day trial evaluating the effects of no bST or bST injections. Treatments were randomly assigned to each animal within one of the tree blocks. The bST did not influence digestibility or performance parameters. Regarding blood results, IGF1 concentration presented an interaction between treatment and day, where bST heifers had the highest IGF1 concentration. Heifers receiving bST also showed increased ribeye area; however, only an experimental day effect for backfat thickness was observed, with greater accumulation of carcass fat on day 84. Heifers receiving bST had lower pixels/mm² on parenchyma, characteristic of greater parenchymal tissue. Moreover, heifers on bST treatment also had reduced pixels/mm2, characteristic of reduced fat pad tissue. Lastly, bST injections did not influence liver and muscle gene expression, nor most genes evaluated in mammary gland tissue, except for IGFBP3 expression, which was greater for bST heifers. In summary, we confirm the efficacy of bST injections to overcome the detrimental effects of high-gain diets on mammary gland growth and to improve lean carcass gain of prepubertal Holstein × Gyr heifers.
Topics: Animals; Cattle; Female; Growth Hormone; Mammary Glands, Animal; Insulin-Like Growth Factor I; Diet; Animal Feed; Sexual Maturation; Body Composition; Animal Nutritional Physiological Phenomena; Insulin-Like Growth Factor Binding Protein 3
PubMed: 38683862
DOI: 10.1371/journal.pone.0300728 -
The Journal of Experimental Biology May 2024Naked mole-rats (NMRs) are among the most hypoxia-tolerant mammals and metabolize only carbohydrates in hypoxia. Glucose is the primary building block of dietary...
Naked mole-rats (NMRs) are among the most hypoxia-tolerant mammals and metabolize only carbohydrates in hypoxia. Glucose is the primary building block of dietary carbohydrates, but how blood glucose is regulated during hypoxia has not been explored in NMRs. We hypothesized that NMRs mobilize glucose stores to support anaerobic energy metabolism in hypoxia. To test this, we treated newborn, juvenile and adult (subordinate and queen) NMRs in normoxia (21% O2) or hypoxia (7, 5 or 3% O2), while measuring metabolic rate, body temperature and blood [glucose]. We also challenged animals with glucose, insulin or insulin-like growth factor-1 (IGF-1) injections and measured the rate of glucose clearance in normoxia and hypoxia. We found that: (1) blood [glucose] increases in moderate hypoxia in queens and pups, but only in severe hypoxia in adult subordinates and juveniles; (2) glucose tolerance is similar between developmental stages in normoxia, but glucose clearance times are 2- to 3-fold longer in juveniles and subordinates than in queens or pups in hypoxia; and (3) reoxygenation accelerates glucose clearance in hypoxic subordinate adults. Mechanistically, (4) insulin and IGF-1 reduce blood [glucose] in subordinates in both normoxia but only IGF-1 impacts blood [glucose] in hypoxic queens. Our results indicate that insulin signaling is impaired by hypoxia in NMRs, but that queens utilize IGF-1 to overcome this limitation and effectively regulate blood glucose in hypoxia. This suggests that sexual maturation impacts blood glucose handling in hypoxic NMR queens, which may allow queens to spend longer periods of time in hypoxic nest chambers.
Topics: Animals; Mole Rats; Homeostasis; Female; Blood Glucose; Hypoxia; Male; Insulin; Insulin-Like Growth Factor I; Glucose
PubMed: 38680085
DOI: 10.1242/jeb.247537 -
Ecotoxicology and Environmental Safety Jun 2024Perfluoroalkyl and polyfluoroalkyl substances (PFASs), as pollutants, can cause palpable environmental and health impacts around the world, as endocrine disruptors, can...
Perfluoroalkyl and polyfluoroalkyl substances (PFASs), as pollutants, can cause palpable environmental and health impacts around the world, as endocrine disruptors, can disrupt endocrine homeostasis and increase the risk of diseases. Chlorinated polyfluoroalkyl ether sulfonate (F-53B), as a substitute for PFAS, was determined to have potential toxicity. Puberty is the stage when sexual organs develop and hormones change dramatically, and abnormal uterine development can increase the risk of uterine lesions and lead to infertility. This study was designed to explore the impact of F-53B on uterine development during puberty. Four-week-old female SD rats were exposed to 0.125 and 6.25 mg/L F-53B during puberty. The results showed that F-53B interfered with growth and sex hormone levels and bound to oestrogen-related receptors, which affected their function, contributed to the accumulation of reactive oxygen species, promoted cell apoptosis and inhibited cell proliferation, ultimately causing uterine dysplasia.
Topics: Animals; Female; Rats; Apoptosis; Cell Proliferation; Endocrine Disruptors; Environmental Pollutants; Fluorocarbons; Rats, Sprague-Dawley; Reactive Oxygen Species; Receptors, Estrogen; Sexual Maturation; Uterus; Alkanesulfonates
PubMed: 38677070
DOI: 10.1016/j.ecoenv.2024.116399 -
Children (Basel, Switzerland) Mar 2024DICER1, a cancer predisposition syndrome (CPS), seems to escape timely diagnosis in pediatric patients. Case report 1: A 16-year-old female patient was referred to the...
BACKGROUND
DICER1, a cancer predisposition syndrome (CPS), seems to escape timely diagnosis in pediatric patients. Case report 1: A 16-year-old female patient was referred to the endocrinology ward due to a large goiter. Her medical history indicated normal sexual maturation, with menarche occurring at 13.5 years. Over the past 2.5 years, she had developed pronounced androgenic symptoms, including a deepened male voice; facial, back, and neckline acne; hirsutism; and menstrual irregularities leading to secondary amenorrhea. A thyroid ultrasound identified a multinodular goiter (MNG) with cystic-solid lesions containing calcifications. An abdominal ultrasound identified a 5.7 × 6.9 cm solid mass in the right adnexal region, displacing the uterus to the left. Histopathological examination confirmed a Sertoli-Leydig cell tumor. The patient was subjected to a total thyroidectomy. Histopathology revealed benign follicular cell-derived neoplasms. Thyroid follicular nodular disease (TFND) was diagnosed bilaterally. DNA analysis using NGS, confirmed via the Sanger method, revealed a pathogenic heterozygotic variant c.2953C>T [p.Gln985*] in exon 18 of the gene. Case report 2: A 12-year-old male patient was admitted to the pediatric surgery unit due to a 33 mL goiter. A month prior to his admission, the patient discovered a palpable nodule in his neck, accompanied by hoarseness. An ultrasound revealed MNG. Molecular analysis revealed a pathogenic heterozygotic variant c.2782C>T [p.Gln928*] in exon 17 of the gene. Subsequently, a total thyroidectomy was performed, and histopathological examination revealed TFND bilaterally.
CONCLUSIONS
Recent advances in genetic evaluation and in histological approaches indicate that MNG/TFND, although rare in the pediatric population, when accompanied by characteristic ultrasound and histopathological features, and by additional features such as androgenization, may warrant assessment also of the gene within CPS molecular panel screening.
PubMed: 38671620
DOI: 10.3390/children11040403 -
PLoS Genetics Apr 2024Animals often grow and develop in unpredictable environments where factors like food availability, temperature, and oxygen levels can fluctuate dramatically. To ensure...
Animals often grow and develop in unpredictable environments where factors like food availability, temperature, and oxygen levels can fluctuate dramatically. To ensure proper sexual maturation into adulthood, juvenile animals need to adapt their growth and developmental rates to these fluctuating environmental conditions. Failure to do so can result in impaired maturation and incorrect body size. Here we describe a mechanism by which Drosophila larvae adapt their development in low oxygen (hypoxia). During normal development, larvae grow and increase in mass until they reach critical weight (CW), after which point a neuroendocrine circuit triggers the production of the steroid hormone ecdysone from the prothoracic gland (PG), which promotes maturation to the pupal stage. However, when raised in hypoxia (5% oxygen), larvae slow their growth and delay their maturation to the pupal stage. We find that, although hypoxia delays the attainment of CW, the maturation delay occurs mainly because of hypoxia acting late in development to suppress ecdysone production. This suppression operates through a distinct mechanism from nutrient deprivation, occurs independently of HIF-1 alpha and does not involve dilp8 or modulation of Ptth, the main neuropeptide that initiates ecdysone production in the PG. Instead, we find that hypoxia lowers the expression of the EGF ligand, spitz, and that the delay in maturation occurs due to reduced EGFR/ERK signaling in the PG. Our study sheds light on how animals can adjust their development rate in response to changing oxygen levels in their environment. Given that hypoxia is a feature of both normal physiology and many diseases, our findings have important implications for understanding how low oxygen levels may impact animal development in both normal and pathological situations.
Topics: Animals; Ecdysone; Signal Transduction; Larva; Drosophila Proteins; Epidermal Growth Factor; Drosophila melanogaster; Hypoxia; Gene Expression Regulation, Developmental; ErbB Receptors; Oxygen; Pupa
PubMed: 38669270
DOI: 10.1371/journal.pgen.1011232 -
PLoS Pathogens Apr 2024The apicomplexan parasite Cryptosporidium is a leading cause of childhood diarrhea in developing countries. Current treatment options are inadequate and multiple...
The apicomplexan parasite Cryptosporidium is a leading cause of childhood diarrhea in developing countries. Current treatment options are inadequate and multiple preclinical compounds are being actively pursued as potential drugs for cryptosporidiosis. Unlike most apicomplexans, Cryptosporidium spp. sequentially replicate asexually and then sexually within a single host to complete their lifecycles. Anti-cryptosporidial compounds are generally identified or tested through in vitro phenotypic assays that only assess the asexual stages. Therefore, compounds that specifically target the sexual stages remain unexplored. In this study, we leveraged the ReFRAME drug repurposing library against a newly devised multi-readout imaging assay to identify small-molecule compounds that modulate macrogamont differentiation and maturation. RNA-seq studies confirmed selective modulation of macrogamont differentiation for 10 identified compounds (9 inhibitors and 1 accelerator). The collective transcriptomic profiles of these compounds indicates that translational repression accompanies Cryptosporidium sexual differentiation, which we validated experimentally. Additionally, cross comparison of the RNA-seq data with promoter sequence analysis for stage-specific genes converged on a key role for an Apetala 2 (AP2) transcription factor (cgd2_3490) in differentiation into macrogamonts. Finally, drug annotation for the ReFRAME hits indicates that an elevated supply of energy equivalence in the host cell is critical for macrogamont formation.
Topics: Cryptosporidiosis; Protozoan Proteins; Life Cycle Stages; Cryptosporidium; Transcription Factors; Animals; Humans; Small Molecule Libraries
PubMed: 38669269
DOI: 10.1371/journal.ppat.1011906 -
Animal Reproduction Science Apr 2024Despite decades of research and handling of semen for use in artificial insemination (AI) and other assisted reproductive technologies, 5-10% of selected boar sires are... (Review)
Review
Despite decades of research and handling of semen for use in artificial insemination (AI) and other assisted reproductive technologies, 5-10% of selected boar sires are still considered sub-fertile, escaping current assessment methods for sperm quality and resilience to preservation. As end-product, the ejaculate (emitted spermatozoa sequentially exposed to the composite seminal plasma, the SP) ought to define the homeostasis of the testes, the epididymis, and the accessory sexual glands. Yet, linking findings in the ejaculate to sperm production biology and fertility is suboptimal. The present essay critically reviews how the ejaculate of a fertile boar can help us to diagnose both reproductive health and resilience to semen handling, focusing on methods -available and under development- to identify suitable biomarkers for cryotolerance and fertility. Bulk SP, semen proteins and microRNAs (miRNAs) have, albeit linked to sperm function and fertility after AI, failed to enhance reproductive outcomes at commercial level, perhaps for just being components of a complex functional pathway. Hence, focus is now on the interaction sperm-SP, comparing in vivo with ex vivo, and regarding nano-sized lipid bilayer seminal extracellular vesicles (sEVs) as priority. sEVs transport fragile molecules (lipids, proteins, nucleic acids) which, shielded from degradation, mediate cell-to-cell communication with spermatozoa and the female internal genital tract. Such interaction modulates essential reproductive processes, from sperm homeostasis to immunological female tolerance. sEVs can be harvested, characterized, stored, and manipulated, e.g. can be used for andrological diagnosis, selection of breeders, and alternatively be used as additives to improve cryosurvival and fertility.
PubMed: 38664134
DOI: 10.1016/j.anireprosci.2024.107476 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... Mar 2024Runt-related transcription factor (RUNX1) is a transcription factor closely involved in hematopoiesis. 1 gene mutation plays an essential pathogenic role in the... (Review)
Review
Runt-related transcription factor (RUNX1) is a transcription factor closely involved in hematopoiesis. 1 gene mutation plays an essential pathogenic role in the initiation and development of hematological tumors, especially in acute myeloid leukemia. Recent studies have shown that RUNX1 is also involved in the regulation of bone development and the pathological progression of bone-related diseases. RUNX1 promotes the differentiation of mesenchymal stem cells into chondrocytes and osteoblasts and modulates the maturation and extracellular matrix formation of chondrocytes. The expression of RUNX1 in mesenchymal stem cells, chondrocytes, and osteoblasts is of great significance for maintaining normal bone development and the mass and quality of bones. RUNX1 also inhibits the differentiation and bone resorptive activities of osteoclasts, which may be influenced by sexual dimorphism. In addition, RUNX1 deficiency contributes to the pathogenesis of osteoarthritis, delayed fracture healing, and osteoporosis, which was revealed by the RUNX1 conditional knockout modeling in mice. However, the roles of RUNX1 in regulating the hypertrophic differentiation of chondrocytes, the sexual dimorphism of activities of osteoclasts, as well as bone loss in diabetes mellitus, senescence, infection, chronic inflammation, etc, are still not fully understood. This review provides a systematic summary of the research progress concerning RUNX1 in the field of bone biology, offering new ideas for using RUNX1 as a potential target for bone related diseases, especially osteoarthritis, delayed fracture healing, and osteoporosis.
Topics: Core Binding Factor Alpha 2 Subunit; Humans; Animals; Cell Differentiation; Bone Development; Chondrocytes; Osteoblasts; Osteoclasts; Mesenchymal Stem Cells; Mice; Bone Diseases; Osteoporosis; Osteoarthritis
PubMed: 38645858
DOI: 10.12182/20240360103 -
Disability and Health Journal Jul 2024Thanks to improved medical care, individuals with spina bifida (SB) live well into adulthood and go through the process of reproductive maturation and the development of...
BACKGROUND
Thanks to improved medical care, individuals with spina bifida (SB) live well into adulthood and go through the process of reproductive maturation and the development of sexual desires. However, access to reproductive counselling and contraceptive use has been reported to be lower for women with physical and intellectual disabilities compared to the general population.
OBJECTIVE
We investigated oral contraceptive use in women with SB, residing in Sweden and how use varies based on the level of lesion and demographic factors.
METHODS
This was a population-based case-control study using annual data from national registers from 2006 to 2015. The sample consisted of 7045 women aged 15-49 years, of which 1173 had a diagnosis of SB. χ tests and logistic regression were used to investigate the study objective.
RESULTS
The rate of oral contraceptive use in women with SB was 24.6 % compared to 34.5 % among the general population. After adjusting for potential confounders women with SB were found to have a lower probability of using oral contraceptives (OR 0.63 95 % CI 0.56-0.71) compared to women without SB. Among women with SB, those with diagnoses Q05.8 (Sacral SB without hydrocephalus) and Q05.9 (SB unspecified) had a higher likelihood of using oral contraceptives compared to other Q05 diagnoses.
CONCLUSION
Women with SB had a lower likelihood of being on oral contraceptives compared to the control group. Further research should investigate if the lower use indicates that oral contraceptives are not an inappropriate method of contraception for women with SB.
Topics: Humans; Female; Sweden; Spinal Dysraphism; Adult; Adolescent; Case-Control Studies; Young Adult; Middle Aged; Contraceptives, Oral; Contraception Behavior; Disabled Persons; Logistic Models; Registries; Contraception
PubMed: 38637232
DOI: 10.1016/j.dhjo.2024.101627 -
PloS One 2024To assess the prevalence and associated factors of Patellofemoral Pain Syndrome (PFPS) in children and adolescents.
OBJECTIVES
To assess the prevalence and associated factors of Patellofemoral Pain Syndrome (PFPS) in children and adolescents.
METHOD
A population-based cross-sectional study was conducted with children and adolescents aged 10 to 18 years, who presented a history of peripatellar and/or retropatellar pain, attending elementary or high school in urban public schools in Natal, Brazil. The sample size was calculated based on a minimum outcome prevalence of 22%.
RESULTS
A prevalence of 24.7% of PFPS was found. There was a positive association of PFPS with active students (p < 0.01; PR: 2.5; CI: 1.4-4.5), low functional capacity (p < 0.01; PR: 8.0; CI: 5.0-12.8), and those classified as pubertal (p < 0.03; PR: 1.8; CI: 1.0-3.2).
CONCLUSION
There was a considerable prevalence of PFPS in children and adolescents, as well as an association between the level of sexual maturation and adjustable determinants, such as the level of physical activity and low functional capacity in this group.
Topics: Child; Humans; Adolescent; Cross-Sectional Studies; Patellofemoral Pain Syndrome; Exercise Therapy; Exercise; Prevalence
PubMed: 38625853
DOI: 10.1371/journal.pone.0300683