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1.
Elife ; 132024 Jul 15.
Article in English | MEDLINE | ID: mdl-39007235

ABSTRACT

The hypothalamic ventral premammillary nucleus (PMv) is a glutamatergic nucleus essential for the metabolic control of reproduction. However, conditional deletion of leptin receptor long form (LepRb) in vesicular glutamate transporter 2 (Vglut2) expressing neurons results in virtually no reproductive deficits. In this study, we determined the role of glutamatergic neurotransmission from leptin responsive PMv neurons on puberty and fertility. We first assessed if stimulation of PMv neurons induces luteinizing hormone (LH) release in fed adult females. We used the stimulatory form of designer receptor exclusively activated by designer drugs (DREADDs) in LeprCre (LepRb-Cre) mice. We collected blood sequentially before and for 1 hr after intravenous clozapine-N-oxide injection. LH level increased in animals correctly targeted to the PMv, and LH level was correlated to the number of Fos immunoreactive neurons in the PMv. Next, females with deletion of Slc17a6 (Vglut2) in LepRb neurons (LeprΔVGlut2) showed delayed age of puberty, disrupted estrous cycles, increased gonadotropin-releasing hormone (GnRH) concentration in the axon terminals, and disrupted LH secretion, suggesting impaired GnRH release. To assess if glutamate is required for PMv actions in pubertal development, we generated a Cre-induced reexpression of endogenous LepRb (LeprloxTB) with concomitant deletion of Slc17a6 (Vglut2flox) mice. Rescue of Lepr and deletion of Slc17a6 in the PMv was obtained by stereotaxic injection of an adeno-associated virus vector expressing Cre recombinase. Control LeprloxTB mice with PMv LepRb rescue showed vaginal opening, follicle maturation, and became pregnant, while LeprloxTB;Vglut2flox mice showed no pubertal development. Our results indicate that glutamatergic neurotransmission from leptin sensitive neurons regulates the reproductive axis, and that leptin action on pubertal development via PMv neurons requires Vglut2.


Subject(s)
Glutamic Acid , Receptors, Leptin , Sexual Maturation , Synaptic Transmission , Animals , Female , Receptors, Leptin/metabolism , Receptors, Leptin/genetics , Mice , Glutamic Acid/metabolism , Neurons/metabolism , Neurons/physiology , Reproduction , Vesicular Glutamate Transport Protein 2/metabolism , Vesicular Glutamate Transport Protein 2/genetics , Luteinizing Hormone/blood , Luteinizing Hormone/metabolism
2.
Braz J Biol ; 84: e282016, 2024.
Article in English | MEDLINE | ID: mdl-38985069

ABSTRACT

Aspects of the reproductive biology of Donax striatus were studied from individuals collected from Gado Bravo Beach in the municipality of Tibau do Norte, state of Rio Grande do Norte, Brazil. Donax striatus is a dioic species without external (on the shell) or internal (gonads) macroscopic dimorphism. Thus, a microscopic examination of the reproductive cells is necessary. For the characterization of the gonadal development stages and determination of the size at first sexual maturity (L50), 30 specimens were selected monthly between February 2021 and January 2022 and submitted to histological processing. The condition index (CI) of each individual was estimated and monthly variations were statistically assessed. The size at first maturity (L50) was estimated to be 14.2 mm in shell length. To foster conservation of the species, catches of individuals larger than 14.2 mm is recommended. The lowest condition indices were found in the dry season, with a greater occurrence of organisms in the elimination stage and exhibiting gonad tissue reorganization. Higher indices were found in the rainy season, with the presence of mature individuals. The continuous nature of gametogenesis in Donax stritatus reflects the influence of rainfall in the region. Males and females have peak gamete elimination with pauses during the year, but with the presence of maturing and eliminating individuals throughout the year. As shellfish gathering targeting Donax striatus is excessive on Gado Bravo Beach in the state of Rio Grande do Norte, it is hoped that the results of the present study can contribute to the establishment of management measures for the activity and conservation strategies for the species.


Subject(s)
Bivalvia , Reproduction , Seasons , Animals , Brazil , Male , Reproduction/physiology , Female , Bivalvia/physiology , Bivalvia/classification , Sexual Maturation/physiology , Gonads/growth & development , Gonads/anatomy & histology , Gonads/physiology
3.
Int J Mol Sci ; 25(13)2024 Jun 27.
Article in English | MEDLINE | ID: mdl-39000192

ABSTRACT

In this study, we used full-sib families to investigate the association between growth and gonad development during first sexual maturation of M. nipponense. We found that male GSI was significantly negatively correlated with growth traits (p < 0.01) and there were no significant correlations between female GSI (Gonadosomatic index) and growth traits (p > 0.05). HSI (Hepatopancreas index) in both males and females showed no significant correlations with growth traits (p > 0.05). We furthermore investigated the association between the specific allele of Mn-CTS L1 polymorphism and gonad development and growth traits. In total, 35 mutation loci were screened and 16 high-quality single-nucleotide polymorphisms (SNPs) loci were obtained after validation. Four and two SNPs proved to be strongly associated with all growth traits in female and male M. nipponense separately, among which A+118T might be a candidate SNP positively associated with large growth traits. Two and one SNPs were screened, respectively, in males and females to associate with GSI, while three SNPs were detected to associate with female HSI, among which A+1379C may be applied as a potential molecular marker for gene-assisted selection to improve both reproduction speed and growth traits in M. nipponense.


Subject(s)
Gonads , Palaemonidae , Polymorphism, Single Nucleotide , Sexual Maturation , Male , Female , Animals , Gonads/growth & development , Gonads/metabolism , Sexual Maturation/genetics , Palaemonidae/genetics , Palaemonidae/growth & development , Alleles , Phenotype
4.
Sci Data ; 11(1): 777, 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-39003290

ABSTRACT

The ovaries and uterus are crucial reproductive organs in mammals, and their coordinated development ensures the normal development of sexual maturity and reproductive capacity. This study aimed to comprehensively capture the different physiological stages of the goat's sexual maturation by selecting four specific time points. We collected samples of ovarian and uterine tissues from five female Jining Gray goats at each time point: after birth (D1), 2-month-old (M2), 4-month-old (M4), and 6-month-old (M6). By combining transcriptomic sequencing of 40 samples (including rRNA-depleted RNA-seq libraries with 3607.8 million reads and miRNA-seq libraries with 444.0 million reads) and metabolomics analysis, we investigated the transcriptomic mechanisms involved in reproductive regulation in the ovary and uterus during sexual maturation, as well as the changes in metabolites and their functional potential. Additionally, we analyzed blood hormone indices and uterine tissue sections to examine temporal changes. These datasets will provide a valuable reference for the reproductive regulation of the ovary and uterus, as well as the regulation of metabolites during sexual maturation in goats.


Subject(s)
Goats , Ovary , Sexual Maturation , Transcriptome , Uterus , Animals , Female , Goats/genetics , Goats/metabolism , Uterus/metabolism , Ovary/metabolism , Ovary/growth & development , Metabolome , Metabolomics
5.
Dev Psychobiol ; 66(6): e22523, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38970242

ABSTRACT

The current literature suggests that relaxin-3/relaxin/insulin-like family peptide receptor 3 (RLN-3/RXFP-3) system is involved in the pathophysiology of affective disorders because the results of anatomical and pharmacological studies have shown that the RLN-3 signaling pathway plays a role in modulating the stress response, anxiety, arousal, depression-like behavior, and neuroendocrine homeostasis. The risk of developing mental illnesses in adulthood is increased by exposure to stress in early periods of life. The available data indicate that puberty is especially characterized by the development of the neural system and emotionality and is a "stress-sensitive" period. The presented study assessed the short-term changes in the expression of RLN-3 and RXFP-3 mRNA in the stress-dependent brain regions in male pubertal Wistar rats that had been subjected to acute stress. Three stressors were applied from 42 to 44 postnatal days (first day: a single forced swim; second day: stress on an elevated platform that was repeated three times; third day: restraint stress three times). Anxiety (open field, elevated plus maze test) and anhedonic-like behavior (sucrose preference test) were estimated during these tests. The corticosterone (CORT) levels and blood morphology were estimated. We found that the RXFP-3 mRNA expression decreased in the brainstem, whereas it increased in the hypothalamus 72 h after acute stress. These molecular changes were accompanied by the increased levels of CORT and anxiety-like behavior detected in the open field test that had been conducted earlier, that is, 24 h after the stress procedure. These findings shed new light on the neurochemical changes that are involved in the compensatory response to adverse events in pubertal male rats and support other data that suggest a regulatory interplay between the RLN-3 pathway and the hypothalamus-pituitary-adrenal axis activity in the mechanisms of anxiety-like behavior.


Subject(s)
Anxiety , Brain , RNA, Messenger , Rats, Wistar , Receptors, G-Protein-Coupled , Stress, Psychological , Animals , Male , Rats , Stress, Psychological/metabolism , Stress, Psychological/physiopathology , Anxiety/metabolism , Anxiety/physiopathology , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/genetics , Brain/metabolism , RNA, Messenger/metabolism , Behavior, Animal/physiology , Relaxin/metabolism , Relaxin/genetics , Receptors, Peptide/metabolism , Receptors, Peptide/genetics , Sexual Maturation/physiology , Nerve Tissue Proteins
6.
PLoS One ; 19(7): e0301427, 2024.
Article in English | MEDLINE | ID: mdl-38968179

ABSTRACT

This study investigates effects of subtle methodological choices on the estimation and biological interpretation of age, growth and reproductive parameters for harbour porpoises. The core analyses are based on a focal Norwegian data set built on samples from 134 harbour porpoises caught incidentally in gillnet fisheries along the Norwegian coast during autumn 2016 and spring 2017. Two contrasting practices for interpretation of seasonal and ontogenetic characteristics of tooth growth layer formation resulted in significant age differences among spring samples of young porpoises and for older animals across seasons. In turn, these differences affected estimates of age at maturity and asymptotic lengths, respectively. We also found significant differences in male age at maturity between two well-documented maturity criteria and between mathematical estimators of age at maturity for both sexes. Two different criteria for corpus albicans classification furthermore resulted in different patterns of ovarian corpora accumulation, which may affect some estimates of fecundity rates and contaminant loads. Both corpora accumulation patterns were also found in reanalysed data from German and Greenlandic porpoises. Based on tabulated overviews of methodological choices made in previous harbour porpoise studies, we argue that several of the issues mentioned above have wider relevance and may affect the validity of meta-analyses as a tool for estimating harbour porpoise sensitivity to extrinsic pressures. Differences in cause of death (COD) composition between data sets can have a similar effect. We demonstrate this in a meta-analysis of published harbour porpoise pregnancy rates, showing significantly higher values for trauma-killed samples compared to samples comprising mixed COD categories. COD also affected the estimated impacts of three previously analysed extrinsic predictors as well as an added predictor for vessel noise levels. We discuss the potential contributions of methodological, biological and anthropogenic factors in shaping observed regional differences in estimates of harbour porpoise life history parameters.


Subject(s)
Phocoena , Animals , Phocoena/physiology , Norway , Female , Male , Seasons , Reproduction/physiology , Sexual Maturation/physiology , Fertility
7.
Reprod Domest Anim ; 59(6): e14646, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38923114

ABSTRACT

Artificial insemination (AI) centres select bulls as calves according to their genetic breeding values and raise them until the first semen collection; yet, a high dropout rate of reared bulls is a problem for AI centres. Potential hormonal indicators of bull sexual maturation (cortisol, dehydroepiandrosterone (DHEA), testosterone, oestradiol, insulin-like growth factor 1 (IGF-1)) were observed and evaluated in relation to the performance parameters to perhaps identify candidate biomarkers allowing an early selection of bulls as suitable sires. Blood samples from 102 German Holstein calves at 4 ± 1, 8 ± 1 and 12 ± 2 months of age from six AI centres were analysed using validated immunoassays for cortisol, DHEA, testosterone, oestradiol and IGF-1. Semen analyses included native and thawed diluted semen. Bulls were classified at the first semen collection into groups with good versus poor performance (GP vs. LP). After 2 years, the subsequent differentiation was done in high (HPP), medium (MPP) and low performance persistency (LPP). Age at first semen collection was an important factor for sperm quality. Cortisol concentrations decreased with age, but the cortisol/DHEA ratio decreased with age only in GP bulls (p < .05). Oestradiol and testosterone concentrations both correlated with libido behaviour (p < .05). Testosterone and IGF-1 concentrations were higher at the time of first semen collection in GP bulls and increased with age (p < .05). In conclusion, testosterone and IGF-1 concentrations at first semen collection are associated with performance at first semen collection and future performance persistency, and might be useful early biomarkers for consistent sperm producing bulls on AI centres.


Subject(s)
Biomarkers , Estradiol , Insemination, Artificial , Semen Analysis , Animals , Male , Cattle/physiology , Insemination, Artificial/veterinary , Biomarkers/blood , Semen Analysis/veterinary , Estradiol/blood , Testosterone/blood , Insulin-Like Growth Factor I/analysis , Insulin-Like Growth Factor I/metabolism , Hydrocortisone/blood , Sexual Maturation/physiology , Semen , Dehydroepiandrosterone/blood
8.
J Mammary Gland Biol Neoplasia ; 29(1): 13, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38916673

ABSTRACT

Conflicting data exist as to how mammary epithelial cell proliferation changes during the reproductive cycle. To study the effect of endogenous hormone fluctuations on gene expression in the mouse mammary gland, we performed bulk RNAseq analyses of epithelial and stromal cell populations that were isolated either during puberty or at different stages of the adult virgin estrous cycle. Our data confirm prior findings that proliferative changes do not occur in every mouse in every cycle. We also show that during the estrous cycle the main gene expression changes occur in adipocytes and fibroblasts. Finally, we present a comprehensive overview of the Wnt gene expression landscape in different mammary gland cell types in pubertal and adult mice. This work contributes to understanding the effects of physiological hormone fluctuations and locally produced signaling molecules on gene expression changes in the mammary gland during the reproductive cycle and should be a useful resource for future studies investigating gene expression patterns in different cell types across different developmental timepoints.


Subject(s)
Epithelial Cells , Gene Expression Profiling , Mammary Glands, Animal , Sexual Maturation , Stromal Cells , Transcriptome , Animals , Female , Mice , Mammary Glands, Animal/cytology , Mammary Glands, Animal/metabolism , Stromal Cells/metabolism , Epithelial Cells/metabolism , Gene Expression Profiling/methods , Sexual Maturation/physiology , Cell Proliferation , Estrous Cycle/genetics
9.
Mol Ecol ; 33(14): e17435, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38877757

ABSTRACT

Linking reproductive fitness with adaptive traits at the genomic level can shed light on the mechanisms that produce and maintain sex-specific selection. Here, we construct a multigenerational pedigree to investigate sex-specific selection on a maturation gene, vgll3, in a wild Atlantic salmon population. The vgll3 locus is responsible for ~40% of the variation in maturation (sea age at first reproduction). Genetic parentage analysis was conducted on 18,265 juveniles (parr) and 685 adults collected at the same spawning ground over eight consecutive years. A high proportion of females (26%) were iteroparous and reproduced two to four times in their lifetime. A smaller proportion of males (9%) spawned at least twice in their lifetime. Sex-specific patterns of reproductive fitness were related to vgll3 genotype. Females showed a pattern of overdominance where vgll3*EL genotypes had three-fold more total offspring than homozygous females. In contrast, males demonstrated that late-maturing vgll3*LL individuals had two-fold more offspring than either vgll3*EE or vgll3*EL males. Taken together, these data suggest that balancing selection in females contributes to the maintenance of variation at this locus via increased fitness of iteroparous vgll3*EL females. This study demonstrates the utility of multigenerational pedigrees for uncovering complex patterns of reproduction, sex-specific selection and the maintenance of genetic variation.


Subject(s)
Genetic Fitness , Genotype , Reproduction , Salmo salar , Animals , Female , Male , Salmo salar/genetics , Reproduction/genetics , Pedigree , Fish Proteins/genetics , Sexual Maturation/genetics
10.
Food Chem Toxicol ; 189: 114773, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38823497

ABSTRACT

Fluoride, a ubiquitous environmental compound, carries significant health risks at excessive levels. This study investigated the reproductive toxicity of fluoride exposure during puberty in mice, focusing on its impact on testicular development, spermatogenesis, and underlying mechanisms. The results showed that fluoride exposure during puberty impaired testicular structure, induced germ cell apoptosis, and reduced sperm counts in mice. Additionally, the SOD activity and GSH content were significantly decreased, while MDA content was significantly elevated in the NaF group. Immunohistochemistry showed an increase in the number of cells positive for GRP78, a key ER stress marker. Moreover, qRT-PCR and Western blot analyses confirmed the upregulation of both Grp78 mRNA and protein expression, as well as increased mRNA expression of other ER stress-associated genes (Grp94, chop, Atf6, Atf4, and Xbp1) and enhanced protein expression of phosphorylated PERK, IRE1α, eIF2α, JNK, XBP-1, ATF-6α, ATF-4, and CHOP. In conclusion, our findings demonstrate that fluoride exposure during puberty impairs testicular structure, induces germ cell apoptosis, and reduces sperm counts in mice. ER stress may participate in testicular cell apoptosis, and contribute to the testicular damage and decreased sperm counts induced by fluoride.


Subject(s)
Apoptosis , Endoplasmic Reticulum Chaperone BiP , Endoplasmic Reticulum Stress , Fluorides , Testis , Animals , Male , Endoplasmic Reticulum Stress/drug effects , Apoptosis/drug effects , Testis/drug effects , Testis/metabolism , Fluorides/toxicity , Mice , Sexual Maturation/drug effects , Heat-Shock Proteins/metabolism , Heat-Shock Proteins/genetics , Sperm Count , Spermatogenesis/drug effects
11.
J Sports Sci ; 42(9): 776-784, 2024 May.
Article in English | MEDLINE | ID: mdl-38869478

ABSTRACT

The purpose of this study was to analyse secular trend in handgrip strength (HGS) in adolescents using an allometric approach and identify the factors associated. The sample comprised 657 and 1004 adolescents (14 to 19 years) in 2007 and 2017/2018, respectively, of public schools in Florianópolis, Brazil. The dependent variable was HGS normalised to body mass and height. Covariance analysis was used to examine secular trends in HGS, and multiple linear regression was used to identify associated factors. The independent variables were sociodemographic, biological, and behavioural factors. Comparison of HGS between surveys indicated a negative secular trend in both sexes (p < 0.001). In boys, there was a positive association of HGS with age and FFM in both surveys. In 2017/18, there was a positive association with sexual maturation and a negative association with sitting time and fat percentage. In girls, FFM was positively associated with HGS in both surveys. In 2007, there were positive associations of HGS with age and vigorous physical activity, whereas, in 2017/18, negative associations were observed with economic level and sitting time. The findings of the present study show a decline in adolescent HGS. And behavioural changes appear to be contributing to declines in HGS.


Subject(s)
Hand Strength , Humans , Adolescent , Male , Hand Strength/physiology , Female , Brazil , Young Adult , Exercise/physiology , Sexual Maturation/physiology , Age Factors , Sex Factors , Sitting Position , Sociodemographic Factors , Cross-Sectional Studies , Socioeconomic Factors , Body Mass Index , Sedentary Behavior
12.
BMC Genomics ; 25(1): 632, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38914933

ABSTRACT

BACKGROUND: Although, oocytes from prepubertal donors are known to be less developmentally competent than those from adult donors it does not restrain their ability to produce full-term pregnancies. The transcriptomic profile of embryos could be used as a predictor for embryo's individual developmental competence. The aim of the study was to compare transcriptomic profile of blastocysts derived from prepubertal and pubertal heifers oocytes. Bovine cumulus-oocyte complexes (COCs) were obtained by ovum pick- up method from prepubertal and pubertal heifers. After in vitro maturation COCs were fertilized and cultured to the blastocyst stage. Total RNA was isolated from both groups of blastocysts and RNA-seq was performed. Gene ontology analysis was performed by DAVID (Database for Annotation, Visualization and Integrated Discovery). RESULTS: A higher average blastocyst rate was obtained in the pubertal than in the pre-pubertal group. There were no differences in the quality of blastocysts between the examined groups. We identified 436 differentially expressed genes (DEGs) between blastocysts derived from researched groups, of which 247 DEGs were downregulated in blastocysts derived from pubertal compared to prepubertal heifers oocytes, and 189 DEGs were upregulated. The genes involved in mitochondrial function, including oxidative phosphorylation (OXPHOS) were found to be different in studied groups using Kyoto Encyclopedia of Genes (KEGG) pathway analysis and 8 of those DEGs were upregulated and 1 was downregulated in blastocysts derived from pubertal compared to prepubertal heifers oocytes. DEGs associated with mitochondrial function were found: ATP synthases (ATP5MF-ATP synthase membrane subunit f, ATP5PD- ATP synthase peripheral stalk subunit d, ATP12A- ATPase H+/K + transporting non-gastric alpha2 subunit), NADH dehydrogenases (NDUFS3- NADH: ubiquinone oxidoreductase subunit core subunit S3, NDUFA13- NADH: ubiquinone oxidoreductase subunit A13, NDUFA3- NADH: ubiquinone oxidoreductase subunit A3), cytochrome c oxidase (COX17), cytochrome c somatic (CYCS) and ubiquinol cytochrome c reductase core protein 1 (UQCRC1). We found lower number of apoptotic cells in blastocysts derived from oocytes collected from prepubertal than those obtained from pubertal donors. CONCLUSIONS: Despite decreased expression of genes associated with OXPHOS pathway in blastocysts from prepubertal heifers oocytes, the increased level of ATP12A together with the lower number of apoptotic cells in these blastocysts might support their survival after transfer.


Subject(s)
Blastocyst , Gene Expression Profiling , Oxidative Phosphorylation , Animals , Cattle , Female , Blastocyst/metabolism , Transcriptome , Sexual Maturation/genetics , Oocytes/metabolism , Gene Expression Regulation, Developmental , Fertilization in Vitro/veterinary
13.
Gen Comp Endocrinol ; 356: 114575, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38908455

ABSTRACT

Reproductive hormones are essential to mating systems, behavior, fertility, gestation, parturition, and lactation in mammals and understanding the role of hormones in these processes is essential for species conservation. Sirenia is a unique order of marine mammals that include manatees, dugongs, and the extinct Steller's sea cow. Extant Sirenian species are all listed as vulnerable due to habitat loss, cold stress, boat strike trauma, harmful algal bloom toxicity, entanglements, and illegal hunting. Therefore, successful reproduction is essential to maintaining and increasing Sirenian populations. Understanding Sirenian reproductive behavior, endocrinology, and mating strategies will aid conservation and management efforts to protect and provide the proper conditions for successful reproduction. The objectives of this review were to synthesize the current knowledge regarding reproductive cycles and endocrinology of Sirenians and identify knowledge gaps for future investigation. The current literature on Sirenian reproductive physiology reports reproductive seasonality, sexual maturation, estrous cyclicity and acyclicity, pregnancy, and sex differences. However, there remain significant knowledge gaps on the cyclicity and pulsatile release of gonadotropins, maturation in females, and characterization of pregnancy hormone profiles throughout gestation. To date, there is no explanation for confirmed pattern for ovarian acyclicity, nor understanding of the function of the numerous accessory corpus luteum described in manatees. Research including a greater number of longitudinal and postmortem studies on a wider variety of wild manatee populations are important first steps. Taken together, understanding the reproductive endocrinology of these vulnerable and threatened species is critical for policy and management decisions to better inform protection initiatives.


Subject(s)
Reproduction , Animals , Female , Reproduction/physiology , Dugong/physiology , Dugong/metabolism , Male , Pregnancy , Sexual Maturation/physiology
14.
Toxicol Appl Pharmacol ; 489: 116981, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38838792

ABSTRACT

Obesity in adult females impairs fertility by altering oxidative stress, DNA repair and chemical biotransformation. Whether prepubertal obesity results in similar ovarian impacts is under-explored. The objective of this study was to induce obesity in prepubertal female mice and assess puberty onset, follicle number, and abundance of oxidative stress, DNA repair and chemical biotransformation proteins basally and in response to 7,12-dimethylbenz(a)anthracene (DMBA) exposure. DMBA is a polycyclic aromatic hydrocarbon that has been shown to be ovotoxic. Lactating dams (C57BL6J) were fed either a normal rodent containing 3.5% kCal from fat (lean), or a high fat diet comprised of 60% kCal from fat, and 9% kCal from sucrose. The offspring were weaned onto the diet of their dam and exposed at postnatal day 35 to either corn oil or DMBA (1 mg/kg) for 7 d via intraperitoneal injection. Mice on the HFD had reduced (P < 0.05) age at puberty onset as measured by vaginal opening but DMBA did not impact puberty onset. Heart, spleen, kidney, uterus and ovary weight were increased (P < 0.05) by obesity and liver weight was increased (P < 0.05) by DMBA exposure in obese mice. Follicle number was largely unaffected by obesity or DMBA exposure, with the exception of primary follicle number, which were higher (P < 0.05) in lean DMBA exposed and obese control relative to lean control mice. There were also greater numbers (P < 0.05) of corpora lutea in obese relative to lean mice. In lean mice, DMBA exposure reduced (P < 0.05) the level of CYP2E1, EPHX1, GSTP1, BRCA1, and CAT but this DMBA-induced reduction was absent in obese mice. Basally, obesity reduced (P < 0.05) the abundance of CYP2E1, EPHX1, GSTP1, BRCA1, SOD1 and CAT. There was greater (P < 0.05) fibrotic staining in obese DMBA-exposed ovaries and PPP2CA was decreased (P < 0.05) in growing follicles by both obesity and DMBA exposure. Thus, prepubertal obesity alters the capacity of the ovary to respond to DNA damage, ovotoxicant exposure and oxidative stress.


Subject(s)
DNA Repair , Mice, Inbred C57BL , Obesity , Ovary , Oxidative Stress , Animals , Female , Oxidative Stress/drug effects , Ovary/drug effects , Ovary/metabolism , Obesity/metabolism , Obesity/chemically induced , Mice , DNA Repair/drug effects , 9,10-Dimethyl-1,2-benzanthracene/toxicity , Biotransformation , Diet, High-Fat/adverse effects , Sexual Maturation/drug effects , Pregnancy
15.
Stress ; 27(1): 2357330, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38775373

ABSTRACT

Why individuals suffer negative consequences following stress is a complex phenomenon that is dictated by individual factors, the timing of stress within the lifespan, and when in the lifespan the consequences are measured. Women who undergo adverse childhood experiences are at risk for lasting biological consequences, including affective and stress dysregulation. We have shown that pubertal adversity is associated with a blunted hypothalamic-pituitary-adrenal axis glucocorticoid response in peripartum humans and mice. In mice, our prior examination of the paraventricular nucleus (PVN) of the hypothalamus showed that pubertal stress led to an upregulation of baseline mRNA expression of six immediate early genes (IEGs) in the PVN of adult, pregnant mice. Separately, we showed that the pregnancy-associated hormone allopregnanolone is necessary and sufficient to produce the blunted stress response phenotype in pubertally stressed mice. In the current study, we further examined a potential mechanistic role for the IEGs in the PVN. We found that in pubertally stressed adult female, but not male, mice, intra-PVN allopregnanolone was sufficient to recapitulate the baseline IEG mRNA expression profile previously observed in pubertally stressed, pregnant mice. We also examined baseline IEG mRNA expression during adolescence, where we found that IEGs have developmental trajectories that showed sex-specific disruption by pubertal stress. Altogether, these data establish that IEGs may act as a key molecular switch involved in increased vulnerability to negative outcomes in adult, pubertally stressed animals. How the factors that produce vulnerability combine throughout the lifespan is key to our understanding of the etiology of stress-related disorders.


Subject(s)
Paraventricular Hypothalamic Nucleus , Stress, Psychological , Transcriptome , Animals , Female , Male , Mice , Stress, Psychological/metabolism , Paraventricular Hypothalamic Nucleus/metabolism , Paraventricular Hypothalamic Nucleus/drug effects , Pregnanolone , Hypothalamus/metabolism , Hypothalamus/drug effects , Pregnancy , Hypothalamo-Hypophyseal System/metabolism , Hypothalamo-Hypophyseal System/drug effects , Sexual Maturation , Genes, Immediate-Early
16.
BMC Genomics ; 25(1): 447, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714941

ABSTRACT

BACKGROUND: The health and size of the testes are crucial for boar fertility. Testicular development is tightly regulated by epigenetics. N6-methyladenosine (m6A) modification is a prevalent internal modification on mRNA and plays an important role in development. The mRNA m6A methylation in boar testicular development still needs to be investigated. RESULTS: Using the MeRIP-seq technique, we identify and profile m6A modification in boar testes between piglets and adults. The results showed 7783 distinct m6A peaks in piglets and 6590 distinct m6A peaks in adults, with 2,471 peaks shared between the two groups. Enrichment of GO and KEGG analysis reveal dynamic m6A methylation in various biological processes and signalling pathways. Meanwhile, we conjointly analyzed differentially methylated and expressed genes in boar testes before and after sexual maturity, and reproductive related genes (TLE4, TSSK3, TSSK6, C11ORF94, PATZ1, PHLPP1 and PAQR7) were identified. Functional enrichment analysis showed that differential genes are associated with important biological functions, including regulation of growth and development, regulation of metabolic processes and protein catabolic processes. CONCLUSION: The results demonstrate that m6A methylation, differential expression and the related signalling pathways are crucial for boar testicular development. These results suggest a role for m6A modification in boar testicular development and provided a resource for future studies on m6A function in boar testicular development.


Subject(s)
Adenosine , Sexual Maturation , Testis , Animals , Male , Testis/metabolism , Testis/growth & development , Adenosine/analogs & derivatives , Adenosine/metabolism , Swine/genetics , Sexual Maturation/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Methylation , Gene Expression Regulation, Developmental , Signal Transduction , Gene Expression Profiling
17.
JAMA Netw Open ; 7(5): e2410253, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38739393

ABSTRACT

Importance: Earlier puberty is associated with adverse health outcomes, such as mental health issues in adolescence and cardiometabolic diseases in adulthood. Despite rapid growth of the Asian American, Native Hawaiian, and Pacific Islander populations in the US, limited research exists on their pubertal timing, potentially masking health disparities. Objective: To examine pubertal timing among Asian American, Native Hawaiian, and Pacific Islander children and adolescents by disaggregating ethnic subgroups. Design, Setting, and Participants: This retrospective cohort study included Asian American, Native Hawaiian, and Pacific Islander youths aged 5 to 18 years assessed for pubertal development at Kaiser Permanente Northern California, a large, integrated health care delivery system. Follow-up occurred from March 2005, through December 31, 2019. Data were analyzed in October 2023. Exposure: Race and ethnicity, categorized into 11 ethnic subgroups: Asian Indian, Chinese, Filipino, Japanese, Korean, Native Hawaiian and Pacific Islander, Other South Asian, Other Southeast Asian, Vietnamese, multiethnic, and multiracial. Main Outcomes and Measures: Pubertal timing was determined using physician-assessed sexual maturity ratings (SMRs). Outcomes included the median age at transition from SMR 1 (prepubertal) to SMR 2 or higher (pubertal) for onset of genital development (gonadarche) in boys, breast development (thelarche) in girls, and pubic hair development (pubarche) in both boys and girls. Results: In this cohort of 107 325 Asian American, Native Hawaiian, and Pacific Islander children and adolescents (54.61% boys; 12.96% Asian Indian, 22.24% Chinese, 26.46% Filipino, 1.80% Japanese, 1.66% Korean, 1.96% Native Hawaiian and Pacific Islander, 0.86% Other South Asian, 3.26% Other Southeast Asian, 5.99% Vietnamese, 0.74% multiethnic, and 22.05% multiracial), the overall median ages for girls' pubarche and thelarche were 10.98 years (95% CI, 10.96-11.01 years) and 10.13 years (95% CI, 10.11-10.15 years), respectively. For boys' pubarche and gonadarche, median ages were 12.08 years (95% CI, 12.06-12.10 years) and 11.54 years (95% CI, 11.52-11.56 years), respectively. Differences between subgroups with earliest and latest median age at onset were 14 months for girls' pubarche, 8 months for thelarche, 8 months for boys' pubarche, and 4 months for gonadarche. In general, Asian Indian, Native Hawaiian and Pacific Islander, and Other South Asian subgroups had the earliest ages at onset across pubertal markers, while East Asian youths exhibited the latest onset. Restricting to those with healthy body mass index did not substantially change the findings. Conclusions and Relevance: In this cohort study of Asian American, Native Hawaiian, and Pacific Islander children and adolescents, pubertal timing varied considerably across ethnic subgroups. Further investigation is warranted to assess whether these differences contribute to observed health disparities in adulthood, such as type 2 diabetes and cardiovascular diseases.


Subject(s)
Asian , Native Hawaiian or Other Pacific Islander , Puberty , Humans , Adolescent , Female , Male , Asian/statistics & numerical data , Child , Native Hawaiian or Other Pacific Islander/statistics & numerical data , Puberty/physiology , Retrospective Studies , Child, Preschool , California , Hawaii , Sexual Maturation/physiology , Pacific Island People
18.
Theriogenology ; 223: 70-73, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38692036

ABSTRACT

Selection to increase body weight in poultry can hamper reproduction traits and compromise production efficiency. Thus, attention to reproduction traits is essential to improving the sustainability of breeding programs. Data from a domestic quail breeding program for meat production were used to estimate genetic parameters. We analyzed five traits: 4-week body weight, age at sexual maturity for males and females, cloacal gland area, female, and male reproductive organs weights. A multi-trait mixed model analysis with fixed effects of generation/hatch was performed, assuming environmental covariance equals zero for sex-limited traits. Heritability estimates range from low to moderate for male sexual maturity and cloacal gland area, and high for other traits. Intersexual genetic correlation for age at sexual maturity is positive, which can lead to correlated responses in the other sex. Reproductive organs weights are genetically correlated with body weight, but not significantly between sexes and nor with sexual maturity. Genetic correlations for the cloacal gland area were positive with body weight and negative with age at sexual maturity of males and females, demonstrating a potential use of this trait for selection with favorable outcomes in reproduction. The use of the cloacal gland area can be used in the same way as the scrotal circumference in mammals, improving female reproduction traits by selecting a trait recorded in males.


Subject(s)
Body Weight , Quail , Sexual Maturation , Animals , Male , Female , Sexual Maturation/genetics , Body Weight/genetics , Quail/genetics , Quail/physiology , Organ Size/genetics , Cloaca
19.
Dev Biol ; 513: 33-49, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38797257

ABSTRACT

Regeneration, regrowing lost and injured body parts, is an ability that generally declines with age or developmental transitions (i.e. metamorphosis, sexual maturation). Regeneration is also an energetically costly process, and trade-offs occur between regeneration and other costly processes such as growth, or sexual reproduction. Here we investigate the interplay of regeneration, reproduction, and developmental stage in the segmented worm Platynereis dumerilii. P. dumerilii can regenerate its whole posterior body axis, along with its reproductive cells, thereby having to carry out the two costly processes (somatic and germ cell regeneration) after injury. We specifically examine how developmental stage affects the success of germ cell regeneration and sexual maturation in developmentally young versus developmentally old organisms. We hypothesized that developmentally younger individuals (i.e. with gametes in early mitotic stages) will have higher regeneration success than the individuals at developmentally older stages (i.e. with gametes undergoing meiosis and maturation). Surprisingly, older amputated worms grew faster and matured earlier than younger amputees. To analyze germ cell regeneration during and after posterior regeneration, we used Hybridization Chain Reaction for the germline marker vasa. We found that regenerated worms start repopulating new segments with germ cell clusters as early as 14 days post amputation. In addition, vasa expression is observed in a wide region of newly-regenerated segments, which appears different from expression patterns during normal growth or regeneration in worms before gonial cluster expansion.


Subject(s)
Germ Cells , Regeneration , Sexual Maturation , Animals , Regeneration/physiology , Sexual Maturation/physiology , Polychaeta/genetics , Polychaeta/physiology
20.
J Anim Sci ; 1022024 Jan 03.
Article in English | MEDLINE | ID: mdl-38820137

ABSTRACT

This experiment evaluated growth, physiological responses, and puberty attainment in beef heifers reared in drylots with a high stocking density, and provided or not with a moderate exercise regimen. A total of 180 heifers (75% Angus × 25% Brahman) were used in this experiment replicated over 2 yr. Each year, 90 heifers were ranked by age (264 ±â€…1 d) and body weight (BW on day -3; 200 ±â€…2 kg) on day 0, and assigned to a) one of six drylot pens (10 × 14 m pens; 10 heifers per pen) with a stocking density of 14 m2/heifer (DENS), or b) one of three pastures (2-ha pastures; 10 heifers per pasture) with a stocking density of 2,000 m2/heifer (CON). Beginning on day 15, three DENS pens were given access to an exercise area (DENS-EX) 3 times/wk (1 h). Negligible forage was available for CON, whereas heifers from all treatments received the same limit-fed diet (~13 kg/heifer daily). Shrunk BW was recorded after 16 h of feed and water withdrawal on days -3 and 225 to calculate BW gain. Temperament was evaluated on days 0, 128, and 224. Heifers were fitted with a pedometer behind their shoulder on day 0 to record physical activity. Pedometer results and blood samples were collected weekly for progesterone analysis. Hair samples from the tail switch were collected every 28 d. Data were analyzed with pen or pasture as an experimental unit, via ANOVA using the MIXED or GLIMMIX procedures of SAS (SAS Inst. Inc., Cary, NC). Heifers from CON had more (P < 0.01) steps per week compared with DENS and DENS-EX (23,973, 6,706, and 12,354 steps/wk, respectively; SEM = 1,247), and DENS-EX heifers had more (P < 0.01) steps per week compared with DENS. No treatment effects (P ≥ 0.91) were detected for heifer BW gain (~0.820 kg/d). Hair cortisol concentrations were greater (P ≤ 0.05) in DENS and DENS-EX compared with CON beginning on day 56. Exit velocity and temperament score were greater (P ≤ 0.05) in DENS compared with DENS-EX and CON on day 224. Puberty attainment was delayed (treatment × day; P < 0.01) in DENS compared with DENS-EX and CON. A greater (P ≤ 0.05) proportion of CON were pubertal by day 105 compared with DENS and DENS-EX (30.0%, 11.6%, and 15.0%, respectively; SEM = 6.5), while a greater (P < 0.05) proportion of CON and DENS-EX were pubertal by day 154 compared to DENS (61.7%, 66.7%, and 43.3%, respectively; SEM = 6.5). Rearing replacement heifers in drylots with high stocking density has detrimental effects on their puberty attainment, and the moderate exercise regimen partially alleviated this negative outcome.


Replacement beef heifers are often reared in drylots with high stocking density to facilitate feeding and management, or to intensify beef production as availability of grazing areas becomes limited. Studies from our group, however, demonstrated that drylot heifers experience delayed puberty attainment compared with heifers reared on pastures. This negative outcome was associated with chronic stress caused by confinement and restricted physical activity; the latter being a key animal welfare factor with direct effects on reproductive development. Based on this rationale, this experiment evaluated growth, stress-related physiological responses, and puberty attainment heifers reared in drylots and exposed or not to a moderate exercise regimen. Moreover, drylot heifers were compared to contemporary cohorts being reared on pasture. As expected, heifers reared in drylots experienced heightened stress-related physiological responses and delayed puberty attainment compared to pasture heifers. Exposing drylot heifers to the moderate exercise regimen did not alleviate the physiological consequences of chronic stress, but lessened the delay in puberty attainment compared with non-exercised drylot cohorts. Therefore, stocking density and exercise opportunities should be considered to improve heifer welfare and reproductive development in intensive drylot systems, as lack of exercise directly contributes to delayed reproductive development of drylot heifers.


Subject(s)
Physical Conditioning, Animal , Sexual Maturation , Animals , Cattle/physiology , Cattle/growth & development , Female , Animal Husbandry/methods , Housing, Animal , Population Density , Progesterone/blood , Hydrocortisone/blood
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