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Biomedicines Jun 2024It is generally assumed that all estrogen-receptor-positive (ER+) breast cancers proliferate in response to estrogen and, therefore, examples of the estrogen-induced... (Review)
Review
It is generally assumed that all estrogen-receptor-positive (ER+) breast cancers proliferate in response to estrogen and, therefore, examples of the estrogen-induced regression of ER+ cancers are paradoxical. This review re-examines the estrogen regression paradox for the Luminal A subtype of ER+ breast cancers. The proliferative response to estrogen is shown to depend on the level of ER. Mechanistically, a window of opportunity study of pre-operative estradiol suggested that with higher levels of ER, estradiol could activate the DREAM-MMB (Dimerization partner, Retinoblastoma-like proteins, E2F4, and MuvB-MYB-MuvB) pathway to decrease proliferation. The response of breast epithelium and the incidence of breast cancers during hormonal variations that occur during the menstrual cycle and at the menopausal transition, respectively, suggest that a single hormone, either estrogen, progesterone or androgen, could activate the DREAM pathway, leading to reversible cell cycle arrest. Conversely, the presence of two hormones could switch the DREAM-MMB complex to a pro-proliferative pathway. Using publicly available data, we examine the gene expression changes after aromatase inhibitors and ICI 182,780 to provide support for the hypothesis. This review suggests that it might be possible to integrate all current hormonal therapies for Luminal A tumors within a single theoretical schema.
PubMed: 38927507
DOI: 10.3390/biomedicines12061300 -
Biology May 2024Premenstrual Dysphoric Disorder (PMDD) is a psychiatric condition characterized by debilitating affective symptomatology in the luteal phase of the menstrual cycle....
Peripheral Blood Mononuclear Cell Expression of Cation-Chloride Cotransporter (CCC) Genes in Premenstrual Dysphoric Disorder (PMDD) across the Menstrual Cycle-A Preliminary Study.
Premenstrual Dysphoric Disorder (PMDD) is a psychiatric condition characterized by debilitating affective symptomatology in the luteal phase of the menstrual cycle. Based on the previous reports that PMDD may be related to GABAergic cellular dysfunction(s), we assessed whether cation-chloride cotransporter (CCC) gene expression across the menstrual cycle is altered in PMDD. As there are limitations in accessing the human CNS to study CCC-encoding genes, we utilized peripheral blood mononuclear cells (PBMCs) as an alternative model. We first sought to replicate previous reports characterizing CCC gene expression patterns in PBMCs of reproductive age women. We subsequently investigated potential distinct CCC mRNA expression patterns in women with PMDD. We collected blood samples across 8 menstrual cycle visits for PBMC separation/RNA extraction to study mRNA expression of four KCCs (KCC1, KCC2, KCC3, KCC4) and two NKCCs (NKCC1, NKCC2) cotransporters. We mostly replicated the earlier gene expression pattern findings, and found that the expression levels of KCC1 were significantly downregulated during the mid-follicular and periovulatory subphases of the menstrual cycle in women with PMDD. The present study shows that PBMCs is a valid model for studying GABAergic mechanisms underlying PMDD.
PubMed: 38927257
DOI: 10.3390/biology13060377 -
Biomolecules Jun 2024Diabetes imposes a huge burden worldwide. Islet transplantation is an alternative therapy for diabetes. However, tacrolimus, a kind of immunosuppressant after organ...
Diabetes imposes a huge burden worldwide. Islet transplantation is an alternative therapy for diabetes. However, tacrolimus, a kind of immunosuppressant after organ transplantation, is closely related to post-transplant diabetes mellitus. Mesenchymal stem cells (MSCs) have attracted interest for their potential to alleviate diabetes. In vivo experiments revealed that human menstrual blood-derived stem cells (MenSCs) treatment improved tacrolimus-induced blood glucose, body weight, and glucose tolerance disorders in mice. RNA sequencing was used to analyze the potential therapeutic targets of MenSCs. In this study, we illustrated that cystathionine β-synthase (CBS) contributed to tacrolimus -induced islet dysfunction. Using β-cell lines (MIN6, β-TC-6), we demonstrated that MenSCs ameliorated tacrolimus-induced islet dysfunction in vitro. Moreover, MenSC reduced the tacrolimus-induced elevation of CBS levels and significantly enhanced the viability, anti-apoptotic ability, glucose-stimulated insulin secretion (GSIS), and glycolytic flux of β-cells. We further revealed that MenSCs exerted their therapeutic effects by inhibiting CBS expression to activate the IL6/JAK2/STAT3 pathway. In conclusion, we showed that MenSCs may be a potential strategy to improve tacrolimus-induced islet dysfunction.
Topics: Humans; STAT3 Transcription Factor; Tacrolimus; Interleukin-6; Animals; Mice; Female; Cystathionine beta-Synthase; Islets of Langerhans; Janus Kinase 2; Insulin-Secreting Cells; Menstruation; Mesenchymal Stem Cells; Signal Transduction; Insulin Secretion; Cell Line
PubMed: 38927074
DOI: 10.3390/biom14060671 -
NPJ Vaccines Jun 2024Following administration of the SARS-CoV-2 vaccine, many women worldwide reported short-term menstrual irregularities. Although menstrual bleeding, "the fifth vital...
Following administration of the SARS-CoV-2 vaccine, many women worldwide reported short-term menstrual irregularities. Although menstrual bleeding, "the fifth vital sign", is experienced by more than 300 million people on any given day worldwide, these changes were only partially studied. Irregular periods are important well beyond fertility and the discomfort they impose; they are associated with the risk of cardiovascular morbidity, chronic diseases, and premature mortality. Pre-clinical examination of the vaccine polymeric envelope indicates its accumulation in the ovaries. The somatic endocrine cells of the ovarian follicle - the granulosa cells (GCs)-participate in the strict hypothalamic-pituitary-ovarian (HPO) feedback loop that governs the menstrual cycle via endocrine and paracrine regulators, as AMH and Inhibins. We aimed to unravel the direct effect of the COVID-19 vaccine on GCs and link their post-vaccine activity to changes in menstrual patterns. Human primary GCs exposed in-vitro to the Pfizer COVID-19 vaccine BNT162b2, demonstrated no change in their viability but altered mRNA transcripts, specifically of the regulatory key factors: InhibinB was upregulated, whereas AMH was downregulated. We further examined pre- and post-vaccination blood samples from individual women and found a 2-3 folds change in the post-vaccination FSH/InhibinB protein level ratio, compared to their pre-vaccination values. This altered expression of InhibinB could significantly impact the HPO axis in vaccinated women and may ultimately influence the endometrium cyclicity, manifested clinically by the commonly reported changes in menstrual bleeding patterns.
PubMed: 38926432
DOI: 10.1038/s41541-024-00911-2 -
Psychoneuroendocrinology Jun 2024Hormonal changes in ovarian hormones like estradiol (E2) during the menstrual cycle affect emotional processes, including emotion recognition, memory, and regulation. So...
Hormonal changes in ovarian hormones like estradiol (E2) during the menstrual cycle affect emotional processes, including emotion recognition, memory, and regulation. So far, the neural underpinnings of the effect of E2 on emotional experience have been investigated using task-based functional magnetic resonance imaging (fMRI) and functional connectivity. In the present study, we examined whether the intrinsic network dynamics at rest (i.e., directed effective connectivity) related to emotion regulation are (1) modulated by E2 levels and (2) linked to behavioral emotion regulation ability. Hence, 29 naturally cycling women participated in two resting-state fMRI scans in their early follicular phase after being administered a placebo or an E2 valerate, respectively. Emotion regulation ability was assessed using a standard emotion regulation task in which participants were asked to down-regulate their emotions in response to negative images. The regions of two functionally predefined neural networks related to emotional down-regulation and reactivity were used to investigate effective connectivity at rest using spectral dynamic causal modelling. We found that E2, compared to placebo, resulted in changes in effective connectivity in both networks. In the regulation network, prefrontal regions showed distinct connectivity in the E2 compared to the placebo condition, while mixed results evolved in the emotional reactivity network. Stepwise regressions revealed that in the E2 condition a connection from the parietal to the prefrontal cortex predicted regulation ability. Our results demonstrate that E2 levels influence effective connectivity in networks underlying emotion regulation and emotional reactivity. Thus, E2 and its potential modification via hormonal administration may play a supporting role in the treatment of mental disorders that show a dysregulation of emotions.
PubMed: 38924828
DOI: 10.1016/j.psyneuen.2024.107103 -
Annals of the Academy of Medicine,... Dec 2023Two decades after the Rotterdam 2003 consensus workshop, there have been considerable advances in elucidating the pathophysiology and epidemiology of polycystic ovary... (Review)
Review
INTRODUCTION
Two decades after the Rotterdam 2003 consensus workshop, there have been considerable advances in elucidating the pathophysiology and epidemiology of polycystic ovary syndrome (PCOS). This has prompted the re-examination of the features that characterise this common condition. Current definitions have led to great heterogeneity in the prevalence of PCOS and have contributed to inconsistent treatment protocols and assessment of therapeutic outcomes. Diagnosis is further complicated by the lack of universal agreement on threshold cut-offs for ovarian dysfunction and ethnic differences in hirsutism; both of which are key features in the definitions that are commonly used currently. These challenges often result in dissatisfaction with medical care among PCOS patients and their physicians.
METHOD
Our factor analysis mathematically identified anti-Mullerian hormone (AMH), associated polycystic ovarian morphology (PCOM) and serum testosterone as the only significant cluster associated with menstrual cycle length variability.
RESULTS AND CONCLUSION
As such, we propose a simplified criteria wherein the presence of at least 2 of the 3 features below would be sufficient to define PCOS: (1) chronic oligo-ovulation or anovulation as indicated by oligomenorrhea (cycle lengths >35 days) or amenorrhea; (2) PCOM: raised AMH ≥37.0 pmol/L instead of transvaginal ultrasound assessment of ovaries; and (3) Androgen excess, or raised serum androgens above the laboratory reference for women. Further studies are required to examine whether the proposed criteria would reduce diagnostic confusion and improve care and outcomes, especially among patients of East Asian ethnicities.
Topics: Humans; Polycystic Ovary Syndrome; Female; Testosterone; Phenotype; Anti-Mullerian Hormone; Asian People; Hirsutism; Oligomenorrhea; Anovulation; Factor Analysis, Statistical; Amenorrhea; Menstrual Cycle; Ovary; East Asian People
PubMed: 38920160
DOI: 10.47102/annals-acadmedsg.202369 -
The Iowa Orthopaedic Journal 2024Female athletes are at increased risk for anterior cruciate ligament (ACL) injuries. The influence of hormonal variation on female ACL injury risk remains ill-defined....
BACKGROUND
Female athletes are at increased risk for anterior cruciate ligament (ACL) injuries. The influence of hormonal variation on female ACL injury risk remains ill-defined. Recent data suggests that the collagen-degrading menstrual hormone relaxin may cyclically impact female ACL tissue quality. This review aims to identify any correlation between menstrual relaxin peaks and rates of female ACL injury.
METHODS
A systematic review was performed, utilizing the MEDLINE, EMBASE, and CINAHL databases. Included studies had to directly address relaxin/female ACL interactions. The primary outcome variable was relaxin proteolysis of the ACL, at cellular, tissue, joint, and whole-organism levels. The secondary outcome variable was any discussed method of moderating relaxin levels, and the clinical results if available.
RESULTS
AllThe numerous relaxin receptors on female ACLs upregulate local collagenolysis and suppress local collagen production. Peak serum relaxin concentrations (SRC) occur during menstrual cycle days 21-24; a time phase associated with greater risk of ACL injury. Oral contraceptives (OCPs) reduce SRC, with a potential ACLprotective effect.
CONCLUSION
A reasonable correlative and plausible causative relationship exists between peak relaxin levels and increased risk of ACL injury in females, and further investigation is warranted. .
Topics: Humans; Relaxin; Female; Anterior Cruciate Ligament Injuries; Menstrual Cycle; Athletic Injuries; Athletes
PubMed: 38919370
DOI: No ID Found -
The Journal of Sports Medicine and... Jul 2024There is mixed evidence on how the menstrual cycle (MC) affects sports performance, with many studies showing variations in performance during different phases of the...
BACKGROUND
There is mixed evidence on how the menstrual cycle (MC) affects sports performance, with many studies showing variations in performance during different phases of the MC, while other evidence shows that the MC's effects on performance may be trivial. Therefore, this exploratory longitudinal monitoring study was designed to investigate MC characteristics and symptoms in a resistance-trained (RT) population to look for associations between measures of well-being and perceived performance metrics across the MC.
METHODS
RT females reported their workout habits, perceived performance metrics, and measures of well-being while tracking their MC with detailed methods via daily check-ins in an app.
RESULTS
Most MC characteristics and symptoms in the present RT population aligned with previous research on the general population. However, the frequency of irregular cycles was higher than in previous research on the general population. The amount of individual variation and within-subject cycle-to-cycle variation in MC characteristics and MC symptoms was also high. All measures of well-being were significantly associated with specific days of the MC, demonstrating a change in well-being based on the timing of the MC. Several perceived performance metrics were significantly associated with changes across the MC, while others were not.
CONCLUSIONS
Overall, with the current evidence as it stands, a highly individualized approach should be taken for any training or performance considerations surrounding the MC due to the high levels of individual variation.
Topics: Humans; Female; Menstrual Cycle; Athletic Performance; Resistance Training; Longitudinal Studies; Adult; Young Adult; Athletes
PubMed: 38916093
DOI: 10.23736/S0022-4707.24.15752-0 -
PeerJ 2024Low energy availability (LEA) causes pathophysiology of the female athlete's body affecting the bone and reproductive health and was observed to have a high prevalence...
BACKGROUND
Low energy availability (LEA) causes pathophysiology of the female athlete's body affecting the bone and reproductive health and was observed to have a high prevalence in recreational female athletes previously. The aim of this study was to analyse the relationship between low energy availability in females questionnaire (LEAF-Q), bone mineral density (BMD), and postural stability in recreational athletes.
METHODS
Recreational female athletes ( = 24, age: 23.71 ± 2.94, Tier I) completed LEAF-Q, postural stability measurement during quiet stance (Zebris platform FDM; GmbH) and their BMD was measured using DXA (Hologic QDR Horizon A). Non-parametric statistical tests were used to analyse the relationships between LEAF-Q, BMD, and postural stability and to compare differences between participants divided by the LEAF-Q score and its subscales.
RESULTS
Risk of LEA was observed in 50% of recreational athletes participating in this study. Up to 46% of participants perceived menstrual bleeding changes related to training and 37.50% experienced menstrual dysfunction. Body composition and body weight fluctuations were observed to affect postural stability and BMD. With the risk score for LEA, the BMD and postural stability were not negatively affected in recreational athletes. However, the high number of recreational athletes in the risk score for LEA and menstrual dysfunctions highlights the need for public health programs aimed to increase awareness of LEA and its health consequences and for open communication about the menstrual cycle. Future longitudinal studies observing LEA, BMD, menstrual function, postural stability, and their interrelationship in female athletes are needed to increase the knowledge of this topic.
Topics: Humans; Female; Bone Density; Athletes; Young Adult; Adult; Postural Balance; Surveys and Questionnaires; Athletic Injuries; Relative Energy Deficiency in Sport; Body Composition; Absorptiometry, Photon
PubMed: 38915384
DOI: 10.7717/peerj.17533 -
Scientific Reports Jun 2024Aim of the study was to evaluate the diagnostic performance and feasibility of transabdominal ultrasound shear wave elastography (SWE) in assessing sonoelastographic...
Aim of the study was to evaluate the diagnostic performance and feasibility of transabdominal ultrasound shear wave elastography (SWE) in assessing sonoelastographic features of the uterus. Twenty-seven premenopausal women were enrolled between 2021 and 2022. Transabdominal SWE measured myometrial stiffness in various uterine segments. Additionally, tissue stiffness of the quadriceps femoris muscle and autochthonous back muscle was measured. Statistical analysis employed non-parametric tests, t test, and a robust mixed linear model. Stiffness values of the uterus and the two investigated muscle types exhibited a similar spectrum: 6.38 ± 2.59 kPa (median 5.61 kPa; range 2.76-11.31 kPa) for the uterine myometrium, 7.22 ± 1.24 kPa (6.82 kPa; 5.11-9.39 kPa) for the quadriceps femoris musle, and 7.43 ± 2.73 kPa (7.41 kPa; 3.10-13.73 kPa) for the autochthonous back muscle. A tendency for significant differences in myometrial stiffness was observed concerning the type of labor mode (mean stiffness of 9.17 ± 1.35 kPa after vaginal birth vs. 3.83 ± 1.35 kPa after Caesarian section, p = 0.01). No significant differences in myometrial stiffness were observed concerning age, BMI, previous pregnancies, uterine flexion and menstrual cycle phase. Transabdominal SWE of uterine stiffness seems to be a fast and practicable method in a clinical setting. Uterine stiffness appears to be largely independent of various factors, except for the mode of delivery. However, further studies are needed to validate these results.
Topics: Humans; Female; Elasticity Imaging Techniques; Adult; Uterus; Myometrium; Pregnancy; Middle Aged; Young Adult
PubMed: 38914622
DOI: 10.1038/s41598-024-65238-3