Search Results (1,652)

Background/Objectives: To analyze how the different phases of the menstrual cycle affect agility in female football players. Methods: A total of 11 female football players were selected from the third tier of the Spanish Football Federation (Third RFEF) and an agility test (t-test) was conducted to measure agility during the three phases of the menstrual cycle: the menstrual, late follicular, and mid-luteal phases. These phases were determined through self-reporting and the use of ovulation test strips for luteinizing hormone detection. Perceptual variables, such as sleep quality, stress, muscle pain, and fatigue, as well as the rating of perceived exertion, were measured. Results: There were no statistically significant differences in agility performance across menstrual cycle phases (F_(2,20) = 1.86; p = 0.18). However, performance in the mid-luteal phase was slightly better compared to other phases. Similarly, no significant differences were found in perceptual variables such as fatigue, sleep quality, stress, and muscle soreness (p > 0.05), although slightly better perceptual responses were observed in the late follicular phase. Conclusions: No significant differences were found when analyzing the influence of menstrual cycle phases on agility, although performance appeared slightly better in the mid-luteal phase. No significant differences were observed in the perceptual variables. Both objective and perceptual variables should be considered in future studies or training programs based on the menstrual cycle. Full article

Melanoma is one of the most aggressive skin cancers, with increasing rates of occurrence. Although it has not traditionally been considered hormonally driven, recent evidence links androgen receptor (AR) signaling to important aspects of melanoma biology, including tumor growth, metastasis, immune evasion, and resistance to therapy. Mechanistically, AR promotes melanoma progression by activating a pro-metastatic gene program, suppressing anti-tumor immune responses, and altering the tumor microenvironment. Additionally, emerging data indicate AR’s involvement in resistance to chemotherapy and immune-based therapies. This review provides a comprehensive overview of AR’s intricate role in melanoma, focusing on its molecular mechanisms, its impact on immune evasion and therapy resistance, and its potential clinical applications. We also assess AR-targeted strategies, including androgen deprivation therapy and AR antagonists, to improve the effectiveness of chemotherapy, targeted therapy, and immunotherapy. Understanding AR’s role in melanoma could lead to new treatment options, particularly for sex-specific patient groups. Full article

Intracerebral hemorrhage (ICH) remains the least treatable form of stroke, with inflammation implicated as a major pathophysiological feature. Hence, this study sought to associate serum proteins and hormones associated with inflammation and ICH outcomes. Patients presenting to Duke University Hospital with computed tomography-verified spontaneous, supratentorial, non-traumatic ICH within 24 h of symptom onset were prospectively recruited. In this pilot study, equal numbers of men and women and Black and White individuals were included and matched by a 6-month modified Rankin Score (mRS). The primary analyses were the correlation of L-ratios (LR; Log2(Day 2/Day 1 concentrations)) of serum gonadal hormones and neuroinflammatory proteins with mRS > 3 at 6 months. A total of 40 participants were included in this pilot study. LRs were significantly higher for C-reactive protein (CRP; p = 0.013) and lower for interleukin-6 (IL-6; p = 0.026) and surfactant protein-D (p = 0.036) in participants with unfavorable outcomes at 6 months after ICH. Further, higher CRP (p = 0.02) and lower IL-6 (p = 0.035) and surfactant protein-D (p = 0.041) LRs were associated with mRS > 3 at 6 months after ICH in multiple logistic regression analyses, adjusted for race and sex. The relationship amongst gonadal hormones, neuroinflammatory proteins, and ICH outcome is complex. In this pilot study, unfavorable outcomes after ICH may have been associated with selected inflammatory biomarkers. A larger scale study is warranted to define interactions between hormones, proteins, and their effects on ICH outcomes. Full article

The ketogenic diet (KD), a high-fat, low-carbohydrate diet, causes profound metabolic adaptations that go beyond energy production and affect endocrine function and thyroid hormone regulation. By shifting the body’s primary fuel source from glucose to fatty acids and ketones, the KD alters insulin signaling, inflammation levels and deiodinase activity, which together affect thyroid hormone metabolism. While this metabolic shift offers potential benefits such as improved insulin sensitivity and reduced systemic inflammation, it also raises concerns about reduced triiodothyronine (T3) levels and altered hypothalamic–pituitary–thyroid (HPT) axis dynamics. This review explores the mechanisms by which the KD affects thyroid function, highlighting both the potential therapeutic benefits and associated risks. Special attention is given to how genetic predispositions, gut microbiota composition and sex-based hormonal differences influence thyroid adaptation to a KD. In addition, there are indications that the influence of the KD on cell metabolism could have therapeutic potential in conditions such as autoimmune thyroid diseases and thyroid cancer. Understanding the delicate balance between the benefits and risks of KD for thyroid health is essential for optimizing its clinical applications and defining individual nutritional strategies. Full article

Background: Ischemia–reperfusion injury (IRI) is a major contributor to acute kidney injury (AKI). While the precise mechanisms of AKI are still incompletely defined, extensive evidence highlights tubular cell injury and death as key factors in its development. Necroptosis has recently emerged as a critical pathway in the pathogenesis of ischemia–reperfusion-induced AKI (IR-AKI). Although sex differences in susceptibility to IR-AKI have been reported, it remains unclear whether there are sex differences in necroptosis dynamics and whether these differences underlie the observed sexual dimorphism in kidney IRI. This study aimed to address these questions. Methods: male and female C57BL/6 J mice were subjected to AKI via ischemia induced by bilateral renal pedicle clamping for 18 min at 37 °C. Plasma, urine, and kidney samples were collected at 0 h, 3 h, 6 h, 12 h, 24 h, 48 h, and 72 h post-reperfusion. Kidney injury and function were assessed by measuring plasma creatinine (PCr), blood urea nitrogen (BUN) levels, and histological damage (PAS and cleaved caspase3 staining). Necroptosis activation was assessed by quantifying phosphorylated forms of key markers: p-RIPK1 and p-MLKL. To explore the role of sex hormones in regulating necroptosis dynamics, ovariectomized female mice were subjected to the same IR-AKI protocol, and their kidney injury and functional outcomes were compared with those of intact counterparts. Results: The PCr was 0.35 ± 0.04 and 0.32 ± 0.06 mg/dL for males and females, respectively, at 3 h of IR. The levels exponentially increased to 2.05 ± 0.18 at 48 h post-reperfusion in the males but only gradually to 0.94 ± 0.13 mg/dL in females. Necroptosis activation began as early as 3 h post-IR in males but was delayed until ~6 h in females. Males exhibited stronger and more sustained necroptosis activation than females, showing elevated phosphorylation levels of pRIPK1 and pMLKL in Western blot. Female sex hormone deficiency exacerbated the female response to IR-induced injury, which reduced the sex difference in the dynamic of the necroptotic activation and subsequent kidney injury. To our knowledge, this is the first study to characterize sex differences in the initiation and progression of necroptosis and subsequent injury in a mouse model of IR-AKI. Conclusions: Our findings reveal distinct temporal patterns of programmed cell death between sexes. Necroptosis-targeted therapies require early intervention in males, which can be delayed in females after IR-AKI, highlighting the need for sex-specific therapeutic windows. Full article

Fish reproduction requires suitable salinity and temperature, as well as sufficient energy. This study investigated temperature and salinity effects on ovarian development of Lateolabrax maculatus and energy metabolism differences between reproduction and growth. Two salinities (4‰ and 30‰) and temperatures (18 ± 1 °C and 30 ± 1 °C) formed four treatments: SWNT (30‰, 30 ± 1 °C), SWLT (30‰, 18 ± 1 °C), FWLT (4‰, 18 ± 1 °C), and FWNT (4‰, 30 ± 1 °C). GSI and sex hormones (FSH, LH, E2, and 17α,20β-DHP) were measured. Transcriptome analysis explored how temperature and salinity regulate ovarian development in L. maculatus, while integrated transcriptomic and targeted energy metabolomic analyses revealed energy metabolism differences between ovary and muscle during this process. The results showed that low salinity (4‰) and low temperature (18 ± 1 °C) synergistically promoted ovarian development in the FWLT group, as indicated by a significant increase in GSI and elevated levels of key sex hormones (FSH, LH, E2, and 17α,20β-DHP). Transcriptome analysis showed that low temperature activated pathways involved in steroidogenesis, oocyte maturation, and meiosis, and genes such as ADCY6, PRKACB, CPEB4, FZD7-A, and CCND2 were significantly upregulated. Salinity changes mainly affected amino acid metabolism, cholesterol metabolism, and the insulin signaling pathway. Genes such as PCSK9 and CKM may regulate ovarian development by regulating hormone synthesis and energy metabolism. Comprehensive transcriptome and metabolome analyses show that glycolysis is downregulated and oxidative phosphorylation is upregulated in the ovary, suggesting that ovarian oogenesis tends to be energized by aerobic metabolism. The TCA cycle may be used more for providing biosynthetic precursors and facilitating the transport of substrates between the mitochondrion and the cytoplasm rather than just as a source of ATP. Muscle tissue relies primarily on glycolysis for rapid energy production and may redistribute energy to the gonads, prioritizing the energy needs of the ovaries and contributing to the dynamic balance between reproduction and growth. This study provides insights into the molecular mechanisms of how environmental factors regulate fish reproduction, providing a theoretical basis and potential molecular targets for the regulation of reproduction and optimization of aquaculture environments. Full article

The Japanese eel (Anguilla japonica) is a valuable aquaculture species in East Asia. However, sex differentiation under culture conditions is often male-biased, complicating the production of female broodstock. This study evaluated the effects of dietary soy isoflavone (SI) supplementation on growth performance, sex differentiation, and sex-specific gene expression in juvenile eels. Juvenile eels (initial mean weight: 1.25 ± 0.02 g) were randomly assigned to 15 tanks, each containing 100 g eels, in a 30-week feeding trial. The control diet (SI0) contained 75% jack mackerel meal. The graded levels (2.5, 5, 7.5, and 10%) of α-Starch were included at the expense of SI, referred to as SI0, SI2.5, SI5, SI7.5, and SI10 diets, respectively. Fish were hand-fed to satiation in triplicate groups of each diet, twice daily for 30 weeks. The SI2.5 and SI5 groups exhibited significantly enhanced final weights and specific growth rates compared to those in the control group (SI0). Histological analysis revealed the presence of differentiating gonads with oogonial proliferation and previtellogenesis in the SI-treated groups, particularly at the 2.5% and 5% inclusion levels. Additionally, the expression of key female-related genes (vasa, cyp19a1a, foxl2a, zp3, and zar1) was significantly upregulated in these groups. In contrast, relatively high SI levels (7.5% and 10%) did not provide any further benefits. These results suggest that low-dose supplementation of dietary SI can enhance feminization and promote growth in juvenile eels, thus offering a potential natural alternative to synthetic hormone treatment for broodstock development. Full article

Background/Objectives: Many women report restrictions on caffeine intake during gestation, but some of these restrictions are withdrawn during the lactation period. Given that both periods have elevated epigenetic plasticity, our aim was to compare the effects of caffeine exposure during each isolated period on offspring metabolism and susceptibility to obesity in response to metabolic overload. Methods: Pregnant Wistar rats received orogastric caffeine (CAF) (25 mg/kg/day) or vehicle during gestation (CAF G) or lactation (CAF L) periods. We evaluated the body mass, adiposity, hormone levels, and food behavior of offspring of both sexes at different ages. Adult animals were subjected to metabolic overload, with fructose solution (10%) offered for ten days. Results/Discussion: CAF G and CAF L dams presented lower T3 levels (−70 and −52%) because of reduced TSH activity in the thyroid gland (−28 and −29%), despite unchanged gland morphology. At weaning, CAF G and CAF L males presented lower T3 levels (−75 and −80%), as did CAF L females (−85%). At puberty, females in the CAF L group showed glucose intolerance. In adulthood, CAF G males exhibited a greater preference for palatable food. In addition, CAF G and CAF L males showed increased feed efficiency, suggesting a greater susceptibility to obesity development. To test this susceptibility, the animals were subjected to fructose overload. Indeed, we observed that despite the absence of a fructose effect in the control group, male CAF G and female CAF L animals showed greater adiposity in response to fructose overload (+43% and +37%, respectively). Conclusions: Caffeine exposure during lactation increases the risk of obesity development among female offspring. However, for male offspring, gestation seems more critical. Full article

Maintaining muscle health is essential for preserving mobility, independence, and quality of life with age. As muscle mass and function decline, the risk of frailty, chronic disease, and disability increases. Sarcopenia, characterized by the progressive loss of muscle mass, strength, and function, is a major contributor to these adverse outcomes in older adults. Early identification and monitoring of sarcopenia are critical for timely intervention to prevent irreversible decline. Muscle biomarkers offer a promising approach for detecting muscle deterioration and guiding treatment strategies. This review explores key biomarkers—including insulin-like growth factor 1 (IGF-1), myostatin, interleukin-6 (IL-6), irisin, interleukin 15 (IL-15), and procollagen type III N-terminal propeptide (P3NP)—that reflect underlying processes such as muscle anabolism, inflammation, metabolism, and remodeling. Alterations in these markers are associated with muscle health status. Furthermore, hormonal status, biological sex, and nutritional factors all modulate biomarker levels, emphasizing the need for personalized assessments. Integrating biomarker analysis into clinical practice has the potential to enhance early diagnosis, inform personalized interventions, and ultimately promote healthy aging by maintaining muscle function and reducing disability risk. Full article

Saline–alkaline water resources are globally widespread, and their rational development offers significant potential to alleviate freshwater scarcity. Saline–alkaline water aquaculture farming not only affects fish growth and survival but also impairs reproductive and developmental functions. Largemouth bass (Micropterus salmoides), an economically important fish, has demonstrated excellent high tolerance to such environments, in order to investigate the effects of alkaline water aquaculture environments on its growth performance, sex hormone levels, gonadal development, and molecular adaptation mechanisms. In this study, largemouth bass were chronically exposed to freshwater (0.55 mmol/L), low alkalinity (10 mmol/L), or high alkalinity (25 mmol/L) and cultured for 80 days. Alkalinity exposure more severely impacted the growth rate of females. High alkalinity significantly increased the hepatosomatic index and decreased the gonadosomatic index in both sexes; moreover, it induced oxidative stress in both sexes, evidenced by reduced superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (TAOC) levels and elevated malondialdehyde (MDA) content. Furthermore, the levels of sex hormones Serum estradiol (E2), 11-ketotestosterone (11-KT), and testosterone were significantly reduced, accompanied by either an elevated ratio of primary oocytes and follicular atresia, or by reduced spermatogenesis. Apoptotic signals appeared in gonadal interstitial cells, with upregulated expression of genes P53, Bax, Casp3, and Casp8. Ultrastructural damage included fewer mitochondria and cristae blurring, further indicating tissue damage causing dysfunction. Transcriptome results showed that oxidative stress damage and energy metabolism imbalance caused by carbonate alkalinity were key to the delayed gonadal development, which was mainly manifested in enrichment of the ECM–receptor interaction and PI3K-Akt signaling pathways in females exposed to low alkalinity, and the GnRH secretion and chemokine signaling pathways in males. Glycosphingolipid biosynthesis and Ferroptosis pathway were enriched in females exposed to high alkalinity, and the Cortisol synthesis and secretion pathway were enriched in males. Overall, high-alkalinity exposure significantly delayed gonadal development in both sexes of largemouth bass, leading to reproductive impairment. Full article

The oral microbiota, long recognized for their role in local pathologies, are increasingly implicated in systemic disorders, particularly cardiovascular disease (CVD). This review focuses on emerging evidence linking oral dysbiosis to neuroglial activation and autonomic dysfunction as key mediators of cardiovascular pathology. Pathogen-associated molecular patterns, as well as gingipains and leukotoxin A from Porphyromonas gingivalis, Fusobacterium nucleatum, Treponema denticola, Aggregatibacter actinomycetemcomitans, etc., disrupt the blood–brain barrier, activate glial cells in autonomic centers, and amplify pro-inflammatory signaling. This glia driven sympathetic overactivity fosters hypertension, endothelial injury, and atherosclerosis. Crucially, sex hormones modulate these neuroimmune interactions, with estrogen and testosterone shaping microbial composition, glial reactivity, and cardiovascular outcomes in distinct ways. Female-specific factors such as early menarche, pregnancy, adverse pregnancy outcomes, and menopause exert profound influences on oral microbial ecology, systemic inflammation, and long-term CVD risk. By mapping this oral–brain–heart axis, this review highlights the dual role of oral microbial virulence factors and glial dynamics as mechanistic bridges linking periodontal disease to neurogenic cardiovascular regulation. Integrating salivary microbiome profiling with glial biomarkers [e.g., GFAP (Glial Fibrillary Acidic Protein) and sTREM2 (soluble Triggering Receptor Expressed on Myeloid cells 2)] offers promising avenues for sex-specific precision medicine. This framework not only reframes oral dysbiosis as a modifiable cardiovascular risk factor, but also charts a translational path toward gender tailored diagnostics and therapeutics to reduce the global CVD burden. Full article

Mugil cephalus is a cosmopolitan marine fish highly relevant from ecological and economic perspectives. Previous studies identified sex-associated variants in the follicle-stimulating hormone receptor (fshr) gene following an XX/XY sex determination (SD) system. However, these variants could not be fully associated with sex in all samples. This suggests other genes and/or environmental factors may be involved in the SD of this species, denoting intraspecific variation. In this study, we constructed a new high-quality genome assembly of M. cephalus. We then re-sequenced the whole genome in males and females from two divergent Mediterranean populations to ascertain whether other genetic variants could also be involved in SD. fshr gene variants showed to only partially explain SD, while a new intronic variant in the sestd1 gene appeared to be associated with SD following a ZZ/ZW system. The presence of other putative candidate SD variants showing significant differences between the two populations suggested a regional pattern of variation in SD in the Mediterranean Sea. The incomplete association of all the identified variants also pointed to a potential role for environmental factors. Full article

Vitamins A, D, E, K, B2, B12, and C play a key role in regulating metabolism and oxidative stress, significantly impacting cardiometabolic health. This review uniquely integrates mechanistic and epidemiological data to examine sex-specific differences in the bioavailability, metabolism, and physiological effects of these vitamins. By linking hormonal and genetic factors with oxidative stress modulation, lipid metabolism, and endothelial function, we outline how individualized vitamin intake strategies may help prevent cardiovascular and metabolic disorders. The paper also identifies natural dietary sources and optimal intake recommendations for each vitamin, emphasizing the importance of tailoring supplementation to sex-related needs. This sex-focused perspective provides a basis for developing personalized nutrition approaches to optimize cardiometabolic outcomes. Full article

Sex hormones’ and menstrual cycle’s effects on cognitive performance remain unclear. This study examined cognitive differences between women across menstrual cycle phases, sex differences between women and men, and hormone–cognition associations. In total, 71 healthy young adults, aged 20–36 (42 women, 29 men), completed standardised cognitive tests measuring attention, processing speed, working memory, and visuospatial abilities. Women were tested twice: during menstrual (low-oestradiol) and pre-ovulatory (high-oestradiol) phases; men once. Hormone levels (oestradiol, progesterone, testosterone) were measured in blood samples via electrochemiluminescence immunoassay (ECLIA). Two analytical strategies were used: (1) within-subject analysis comparing women between phases, and (2) between-group comparison across three groups—women in menstrual phase, pre-ovulatory phase, and men. Women performed better during pre-ovulatory versus menstrual phase in working memory (Digit span forward: p = 0.04; Digit span backwards max: p = 0.02) and attention switching (Trail Making Test B: p = 0.01). Sex differences in processing speed were observed only during the menstrual phase (Trail Making Test A: p = 0.03; Stroop B: p = 0.04), but not in the pre-ovulatory phase. Positive correlations between oestradiol/progesterone and cognitive performance were found in men, while complex bidirectional relationships emerged in women during the menstrual phase only. Testosterone showed no significant correlations. These findings highlight hormonal status effects on cognitive sex differences. Full article

Background and Clinical Significance: The 45,X0/46,XY mosaic karyotype is categorized as a disorder of sex development and can lead to atypical sexual development. Latent mosaicism involving Y chromosomal segments may be much more prevalent than previously assumed, according to a growing number of findings. This primarily depends on how sensitive cytogenetic methods are—such as traditional karyotype screening, FISH methods, or molecular analyses. Case Presentation: We present the case of a 10-week-old infant with hermaphroditic external genitalia. During pregnancy, ultrasonography revealed severe fetal development difficulties, including severe widespread edema. An abnormal 45,X0/46,XY mosaic karyotype was discovered during a genetic amniocentesis conducted during the 16th week of pregnancy. The infant was born in average general condition at 39 + 6 weeks of gestation. Physical examination of the infant revealed features of facial dysmorphia, webbed neck, and hermaphroditic external genitalia. The testicle was palpable on the left side, but the gonad was absent on the right. Laboratory tests revealed a typical hormonal profile of the mini-puberty period in boys. Moreover, a hormone panel and thyroid ultrasound were performed; congenital hypothyroidism was diagnosed. Three separate independent sources of biological material were used in cytogenetic analysis to determine the karyotype: skin fibroblasts (to confirm tissue mosaicism), oral epithelial cells (FISH), and peripheral blood lymphocytes. It showed that a mosaic occurred very early in embryogenesis by confirming the existence of karyotypes 45,X and 46,XY in various tissues (mosaic tissue distribution). Conclusions: Tissue mosaicism should be compared to the analysis of tissues from other embryonic origins, including blood and oral tissue. Support for gender identity and treatment decisions, including the prediction of the future risk of gonadoblastoma, as well as multidisciplinary care, is necessary. Full article