Natural Estrogens Research Articles

Repair effect of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles on ovarian injury induced by cisplatin.

Small extracellular vesicles (sEVs) secreted by human umbilical cord have therapeutic effects on various degenerative diseases. However, the characteristics and potential functions of human umbilical cord mesenchymal stem cells (huMSCs)-derived sEVs, especially the role of premature ovarian failure (POF), are poorly understood. Here, we isolated and characterized huMSCs and their sEVs. huMSCs highly expressed CD73, CD90, and CD105. huMSC-sEVs showed typical exosomal features, highly expressing CD9, TSG101, and CD63. It was shown that huMSC-sEVs could be taken up by granulosa cells (GCs) and damaged ovarian tissue, which increased the levels of hormone secretion and reduced GCs apoptosis. We further confirmed that the levels of follicle-stimulating hormone in rat serum decreased dramatically, while the levels of estrogen (E2）and anti-mullerian hormone (AMH) increased significantly with the treatment of huMSC-sEVs. Meanwhile, huMSC-sEVs treatment greatly reduced cell apoptosis and autophagy, while increased the phosphorylation levels of p-PI3K and p-Akt. Therefore, treatment with huMSC-sEVs significantly inhibited GCs apoptosis, improved ovarian morphology, promoted follicular development, inhibited follicular over-atresia, and improved ovarian reserve capacity in POF rats. Our study verified that activation of PI3K/Akt signaling pathway and regulation of cellular autophagy, thus reducing GCs death, are the mechanisms by which huMSC-sEVs restore ovarian tissue function.

Advances on T cell immunity in bone remodeling and bone regeneration.

Bone remodeling and bone regeneration are essential for preserving skeletal integrity and maintaining mineral homeostasis. T cells, as key members of adaptive immunity, play a pivotal role in bone remodeling and bone regeneration by producing a range of cytokines and growth factors. In the physiological state, T cells are involved in the maintenance of bone homeostasis through interactions with mesenchymal stem cells, osteoblasts, and osteoclasts. In pathological states, T cells participate in the pathological process of different types of osteoporosis through interaction with estrogen, glucocorticoids, and parathyroid hormone. During fracture healing for post-injury repair, T cells play different roles during the inflammatory hematoma phase, the bone callus formation phase and the bone remodeling phase. Targeting T cells thus emerges as a potential strategy for regulating bone homeostasis. This article reviews the research progress on related mechanisms of T cells immunity involved in bone remodeling and bone regeneration, with a view to providing a scientific basis for targeting T cells to regulate bone remodeling and bone regeneration.

Estrogen Hormones' Implications on the Physiopathology of Temporomandibular Dysfunction.

Background/Objectives: Temporomandibular dysfunction syndrome consists of several disorders of the masticatory system, namely those of the muscles, the joint itself, as well as the dental and periodontal system. This syndrome is often characterized by pain and an inability to perform functions within the dental-maxillary apparatus, which creates a certain degree of disability in patients. Women are more susceptible to this syndrome than men and hormonal factors, particularly estrogen, are central to its etiology and physiopathology. Methods: A comprehensive literature search was conducted using PubMed/MEDLINE, Scopus, Embase, and Web of Science databases regarding articles published from January 2008 to December 2023. Two authors conducted searches in the mentioned databases based on a pre-established search strategy using agreed-upon keywords. Additionally, each review author performed the selection process of eligible studies based on established inclusion criteria. The Newcastle-Ottawa scale and Risk of Bias tool 2 were used to assess each article for its methodological quality. Results: Of the 1030 records found in the four bibliographic databases, 22 studies were included in this review. Polymorphism in the alpha estrogen receptor appears to be significantly more prevalent in women with temporomandibular dysfunction, suggesting a genetic predisposition. There is a significant role of estrogen in the physiopathology of TMD-related pain. Women with polycystic ovary syndrome (PCOS) have a significantly higher incidence of TMD, accompanied by elevated inflammatory factors and decreased progesterone levels. In premenopausal women, there is scientific relevance to the association between beta-estradiol levels and TMD development and progression. The effects of estrogen hormones on temporomandibular dysfunction remain highly debated and challenging. Conclusions: These findings emphasize the importance of considering hormonal factors, genetic predisposition, and reproductive life stages in understanding and managing temporomandibular dysfunction. Further research is needed to elucidate the specific mechanisms underlying these associations.

Prediction of Endocrine-Disrupting Chemicals Related to Estrogen, Androgen, and Thyroid Hormone (EAT) Modalities Using Transcriptomics Data and Machine Learning.

Endocrine-disrupting chemicals (EDCs) are chemicals that can interfere with homeostatic processes. They are a major concern for public health, and they can cause adverse long-term effects such as cancer, intellectual impairment, obesity, diabetes, and male infertility. The endocrine system is a complex machinery, with the estrogen (E), androgen (A), and thyroid hormone (T) modes of action being of major importance. In this context, the availability of in silico models for the rapid detection of hazardous chemicals is an effective contribution to toxicological assessments. We developed Qualitative Gene expression Activity Relationship (QGexAR) models to predict the propensities of chemically induced disruption of EAT modalities. We gathered gene expression profiles from the LINCS database tested on two cell lines, i.e., MCF7 (breast cancer) and A549 (adenocarcinomic human alveolar basal epithelial). We optimized our prediction protocol by testing different feature selection methods and classification algorithms, including CATBoost, XGBoost, Random Forest, SVM, Logistic regression, AutoKeras, TPOT, and deep learning models. For each EAT endpoint, the final prediction was made according to a consensus prediction as a function of the best model obtained for each cell line. With the available data, we were able to develop a predictive model for estrogen receptor and androgen receptor binding and thyroid hormone receptor antagonistic effects with a consensus balanced accuracy on a validation set ranging from 0.725 to 0.840. The importance of each predictive feature was further assessed to identify known genes and suggest new genes potentially involved in the mechanisms of action of EAT perturbation.

Phaleria macrocarpa Fruit Flavonoid Extract on Estrogen Receptor Alpha Expression in Ovariectomized Mice

Menopause signifies the cessation of ovarian function, presenting significant health challenges for women globally. Hormonal shifts during menopause impact various systems, including cardiovascular and reproductive health. Changes in reproductive organs increase susceptibility to health issues, necessitating effective management strategies. This study used a true experimental method with a randomized post-test-only control group design to investigate the potential of Phaleria macrocarpa fruit extract, which contains flavonoids, to modulate Estrogen Receptor Alpha (ERa) expression in menopausal mice. Following ovariectomy (OVX), mice treated with flavonoid showed increased ERa expression, with the highest expression observed at a dose of P2 (7.5 mg/mice/day), approaching those in non-OVX control (K-) with a percentage difference of 29.82%. Compared to the OVX control group (K+), the percentage increase was 2387.74%. Therefore, the P2 dose is considered the optimum dose. Regression analysis revealed a significant correlation of 43.3% between flavonoid dosage and ERa expression (p < 0.05). These findings suggest flavonoids as promising natural Selective Estrogen Receptor Modulators (SERMs) for managing menopausal symptoms and reducing endometrial disease risk with ERa modulation. Further research is needed to elucidate the mechanisms of flavonoids, including molecular pathways such as ligand binding and transcription, interactions with other hormones like progesterone, long-term effects, and potential clinical applications. To initiate clinical trials, the author established the P1 dose (3.75 mg/mice/day), which demonstrated expression levels approaching the effects produced by P2. Overall, flavonoids offer potential therapeutic benefits in addressing menopausal health concerns, with the identified optimal dosage providing valuable guidance for future studies and clinical interventions.

Raynaud's Phenomenon: A Current Update on Pathogenesis, Diagnostic Workup, and Treatment.

Raynaud's phenomenon (RP) is a condition characterized by episodic, excessive vasoconstriction in the fingers and toes, triggered by cold or stress. This leads to a distinctive sequence of color changes in the digits. Pallor indicates reduced blood flow due to oxygen deprivation, while erythema appears as reperfusion. RP can be primary, with no identifiable underlying cause, or secondary, associated with other conditions. These conditions include autoimmune diseases, most commonly systemic sclerosis, vascular diseases; and neurological conditions. While the exact cause of RP remains unclear, genetic and hormonal (estrogen) factors are likely contributors. The pathogenesis of RP involves a complex interaction between the vascular wall, nerves, hormones, and humoral factors, disrupting the balance between vasoconstriction and vasodilation. In primary RP, the vascular abnormalities are primarily functional. However, in secondary RP, both functional and structural components occur in blood vessels. This explains why digital tissue damage frequently occurs in secondary RP but not primary RP. Diagnosis of RP is primarily clinical. Recent advancements in imaging techniques have aided in diagnosis and monitoring, but nail fold capillaroscopy remains the gold standard for distinguishing between primary and secondary RP. If there are signs of acute ischemic injury, vascular imaging, particularly preoperatively, is crucial to rule out other vaso-occlusive conditions. Management of RP focuses on alleviating symptoms and preventing tissue damage. Vasodilator medications are the first-line treatment when general measures like warmth and stress management are not sufficient. Dihydropyridine calcium channel blockers (CCBs), such as nifedipine, are commonly used for vasodilation. Phosphodiesterase-5 inhibitors and prostaglandin analogs are alternative options for patients who do not respond to CCBs or have ischemic tissue damage. Bosentan, an endothelin-1 receptor antagonist, has shown effectiveness in treating and preventing digital ulcers, especially in patients with multiple ulcers. For severe cases, botulinum toxin injections or sympathectomy surgery can be used to control RP symptoms. However, botulinum toxin injections require repeated administration, and sympathectomy's long-term effectiveness is uncertain. Fat grafting is a promising surgical therapy for promoting healing and preventing tissue injury.

Current treatment for male infertility: an umbrella review of systematic reviews and meta-analyses.

This umbrella review aimed to summarize and provide a general evaluation of the effectiveness of current treatments for male infertility and assess the quality of evidence and possible biases. An umbrella review of systematic reviews and meta-analyses available in PubMed, Web of Science, and Scopus, covering studies published up to October 2023, was conducted. Sperm concentration, morphology, and motility were used as endpoints to evaluate the effectiveness of the treatments. Of 2998 studies, 18 published meta-analyses were extracted, yielding 90 summary effects on sperm concentration ( n = 36), sperm morphology ( n = 26), and sperm motility ( n = 28) on 28 interventions. None of the meta-analyses were classified as having low methodological quality, whereas 12 (66.7%) and 6 (33.3%) had high and moderate quality, respectively. Of the 90 summary effects, none were rated high-evidence quality, whereas 53.3% ( n = 48), 25.6% ( n = 23), and 21.1% ( n = 19) were rated moderate, low, and very low, respectively. Significant improvements in sperm concentration, morphology, and motility were observed with pharmacological interventions (N-acetyl-cysteine, antioxidant therapy, aromatase inhibitors, selective estrogen receptor modulators, hormones, supplements, and alpha-lipoic acid) and nonpharmacological interventions (varicocele repair and redo varicocelectomy). In addition, vitamin supplementation had no significant positive effects on sperm concentration, motility, or morphology. Treatments for male infertility are increasingly diverse; however, the current evidence is poor because of the limited number of patients. Further well-designed studies on single treatment and high-quality meta-analysis of intertreatment comparisons are recommended.

Joint Inflammation Correlates with Joint GPR30 Expression in Males and Hippocampal GPR30 Expression in Females in a Rat Model of Rheumatoid Arthritis.

It is not entirely clear how the interaction between joint inflammation and the central nervous system (CNS) response in rheumatoid arthritis (RA) works, and what pathophysiology underlies the sex differences in coexisting neuropsychiatric comorbidities. It is known that estrogen hormones reduce inflammation in RA and that this occurs mainly via the stimulation of G protein-coupled receptor-30 (GPR30), also known as G protein-coupled estrogen receptor (GPER) 1. However, changes in GPR30 expression and sex differences induced by local and systemic inflammation in RA are not yet known. Our aim was to reveal sex differences in the expression and association of joint GPR30 with local and systemic inflammation, clinical course and furthermore with hippocampal GPR30 expression during pristane-induced arthritis (PIA) in Dark Agouti (DA) rats, an animal model of RA. Furthermore, we demonstrated sex-specific differences in the association between joint and systemic inflammation and hippocampal microglia during PIA. Our results suggest sex-specific differences not only in the clinical course and serum levels of pro-inflammatory cytokines but also in the expression of GPR30. Female rats show greater synovial inflammation and greater damage to the articular cartilage compared to males during PIA attack. Male rats express higher levels of synovial and cartilaginous GPR30 than females during PIA, which correlates with a less severe clinical course. The correlation between synovial and cartilaginous GPR30 and joint inflammation scores (Krenn and Mankin) in male rats suggests that the more severe the joint inflammation, the higher the GPR30 expression. At the same time, there is no particular upregulation of hippocampal GPR30 in males. On the other hand, female rats express higher levels of neuroprotective GPR30 in the hippocampus than male rats at the basic level and during PIA attack. In addition, females have a higher number of Iba-1+ cells in the hippocampus during PIA attack that strongly correlates with the clinical score, serum levels of IL-17A, and Krenn and Mankin scores. These results suggest that male rats are better protected from inflammation in the joints and female rats are better protected from the inflammation in the hippocampus during a PIA attack, independently of microglia proliferation. However, in the remission phase, synovial GPR30 expression suddenly increases in female rats, as does hippocampal GPR30 expression in males. Further experiments with a longer remission period are needed to investigate the molecular background of these sex differences, as well as microglia phenotype profiling.

Peripheral arterial disease in women.

Peripheral arterial disease (PAD) represents one of the most frequent manifestations of atherosclerosis in men and women. In both sexes, PAD is related to classical risk factors of atherosclerosis, which are similarly distributed, but some additional factors determine differences between men and women. More frequent asymptomatic disease in women than in men and less frequent screening in women may result in a false underestimation of the prevalence of PAD in women. All these factors may cause delayed diagnosis and treatment of PAD in women. Estrogen hormones have vasoprotective properties that lower the prevalence of atherosclerosis in women of younger age. However, estrogen probably does not have a protective role against the development of cardiovascular disease in women of an older age. Hormone replacement therapy (HRT) of less than one year does not appear to reduce the odds of developing PAD in postmenopausal women. It may even increase the risk of morbidity from vascular interventions. However, some studies indicated that HRT for more than one year significantly decreases the risk of PAD if administered early after the last menstruation. Also, treatment of PAD in women differs to some extent from men.

Sex Differences in Alcohol Use: Is It All About Hormones?

Risky alcohol use and alcohol use disorders (AUD) are a rising problem in women, yet a major disparity in our understanding of what drives alcohol consumption in women remains. Historically biomedical research has focused on male subjects; however, recent increases in reporting of females, have highlighted major differences between the sexes. Here we review the current literature of the effect of gonadal steroid hormones (estrogens, androgens, and progestins), neurosteriods, and neurobiological factors on alcohol use in clinical and preclinical studies of both sexes. Further, we briefly discuss how fundamental sex differences in genetics, metabolism, neuroimmune, and stress responses may influence sex differences in alcohol intake. Comparing the sexes could aid in the discovery of novel therapeutics to treat AUD, and implementation of current treatment options in women.

Detection of 17-[formula omitted]-Ethinylestradiol with Bio-Functionalized tapered optical fiber sensor

This paper presents the utilization of tapered optical fiber (TOF) biosensor for the detection of 17-α-ethinylestradiol (EE2), an estrogen hormone. TOF with a waist diameter of 12 μm was fabricated from single mode fiber using heat and pull method. The tapered area was used as the sensing interface between the evanescent waves propagating around the fiber due to its unique geometry and the attached molecules on the tapered surface. EE2 antibodies were used as biorecognition molecules towards the targeted analyte, EE2. When tested with different concentrations of EE2 within the range of 0.1 ng/L – 1 mg/L, the developed sensor attained a detection limit of 1 ng/L with a sensitivity value of 1.088 nm/ngL-1 within the operation range of 1 – 10 ng/L. The specificity of the sensor was validated by testing the developed sensor with estrone (E1) and no significant wavelength shift was observed. These findings highlight the potential of our approach for sensitive and selective detection of EE2.

The Effect of Giving Warm Ginger in Reducing Emesis Gravidarum in 1st Trimester Pregnant Women

Due to an increase in the hormone estrogen and progesterone produced by Human Chronic Gonadotropin (HCG), which causes emesis gravidarum, during pregnancy, the mother experiences hormonal changes. This study means to decide the impact of giving warm ginger in diminishing emesis gravidarum in pregnant ladies in the principal trimester PMB Lilis Nurhasanah, S.ST., Keb., Bd. SKM 2024. This exploration utilizes a Semi Trial technique with a One Gathering Pretest Posttest plan. This study's participants were pregnant women in their first trimester who had emesis gravidarum at PMB Lilis Nurhasanah, S.ST., Keb., Bd. SKM upwards of 30 respondents. The examining strategy in this examination is Complete Testing. Shapiro-Wilk normality test analysis yielded sig data (0.05). The Wilcoxon test has a p-worth of 0.000, and that implies there is an impact of giving warm ginger in diminishing emesis gravidarum in first trimester pregnant ladies. This end shows that there is an impact of giving warm ginger in lessening emesis gravidarum in first trimester pregnant ladies at PMB Lilis Nurhasanah, S.ST., Keb., Bd. SKM 2024.

REPRODUCTIVE AGEING: Altered histone modification landscapes underpin defects in uterine stromal cell decidualization in aging females.

Advanced maternal age is associated with a higher rate of pregnancy complications that are unrelated to karyotypic abnormalities of the oocyte. This study shows that the murine uterine stroma undergoes profound epigenetic changes affecting active and repressive histone modification profiles that are associated with impaired endometrial functionality and underpin the decline in reproductive performance of aged females. Decidualization describes the transformation of the uterine stroma in response to an implanting embryo, a process critical for supporting the development of the early embryo, for ensuring normal placentation and ultimately for a healthy reproductive outcome. Maternal age has been found to impede the progression of decidualization, heightening the risk of reproductive problems. Here, we set out to comprehensively characterize this deficit by pursuing transcriptomic and epigenomic profiling approaches specifically in the uterine stromal cell (UtSC) compartment of young and aged female mice. We find that UtSCs from aged females are globally far less responsive to the decidualization stimulus triggered by exposure to the steroid hormones estrogen and progesterone. Despite an overall transcriptional hyperactivation of genes that are differentially expressed as a function of maternal age, the hormonally regulated genes specifically fail to be activated in aged UtSCs. Moreover, even in their unstimulated 'ground' state, UtSCs from aged females are epigenetically distinct, as determined by genomic enrichment profiling for the active and repressive histone marks H3K4me3 and H3K9me3, respectively. We find that many hormone-inducible genes exhibit a profound lack of promoter-associated H3K4me3 in aged UtSCs, implying that a significant enrichment of active histone marks prior to gene stimulation is required to enable the elicitation of a rapid transcriptional response. With this combination of criteria, our data highlight specific deficits in epigenetic marking and gene expression of ion channels and vascular markers. These results point to fundamental defects in muscle-related and perivascular niche functions of the uterine stroma with advanced maternal age.

Case Report: Effect of Ajwa Date Consumption on LDL Levels in Perimenopausal Women

During perimenopause, there can be a decrease in estrogen production, which indicates the end of a woman’s reproductive years. The production of the hormone estrogen that continues to decrease will cause hypercholesterolemia. Decrease in LDL cholesterol levels can be increased by giving antioxidant properties, which are rich in vitamin C and contain flavanoids and phenolics that function as antioxidants. The method used in this study is Literature Review with Design Narrative Review. The result from the literature it was found the effect of giving ajwa dates (Phoenix Dactylifera L) before and after administration showed a change, namely a decrease in LDL levels after giving ajwa dates. This is because ajwa dates contain flavanoids, phenolics, and plant sterols that function as antioxidant that can prevent the formation of lipid peroxidation. The conclusion based on the results of the literature review, it can be concluded that giving ajwa dates to perimenopause women decreased LDL levels where ajwa dates have antioxidant functions to prevent lipid peroxidation to reduce LDL. The suggestion from the study is necessary to conduct further research on the effect of consumption of ajwa dates on LDL levels in perimenopause women using experimental methods of pretest and posttest design.

A Global Inventory of Natural and Synthetic Estrogens in Aquatic Systems.

Estrogens are a group of endocrine disruptors that are recognized as a threat to the world's ecosystems and are easily transported through aquatic systems from mainly anthropogenic sources. To illustrate this growing problem, we have compiled a global overview of measured concentrations of natural and synthetic estrogens restricted to freshwater systems (lakes, rivers, and lagoons) and marine coastal and open ocean environments, focusing on estrone (E1), 17$\upbeta$-estradiol (E2), estriol (E3), and 17$\upalpha$-ethinylestradiol (EE2). We found that the cumulative risk quotient is high at 65% of 400 sampled sites, highlighting that estrogen pollution is a major environmental concern. Our investigation revealed that almost no information is available on the concentration levels of E1, E2, E3, and EE2 for the open ocean areas. However, their occurrence in all systems, including open seas, suggests that estrogens are not completely degraded during transport to and within the environment and may be more persistent than previously thought.

Hormone replacement therapy did not alleviate temporomandibular joint inflammatory pain in ovariectomized rats.

This study had the aim of examining the relationships between variations in estrogen levels resulting from ovariectomy, and estrogen hormone replacement therapy (HRT) in rats subjected to an orofacial inflammatory pain model. Eighty adult female Wistar rats were initially divided into 2 groups: Sham or ovariectomy (OVX-D1). Seven days later (D7), the rats were subjected to an unilateral infiltration of Freund's Complete Adjuvant (CFA) or saline solution into the right temporomandibular joint (TMJ). Then, rats received 17β-estradiol (28µg/kg/day) or placebo for 21days (D10-D31). Nociception was evaluated by the von Frey (VF) and the Hot Plate (HP) tests, and depressive-like behavior by the Forced Swimming (FS) test. On D32 all rats were euthanized and serum, hippocampus and brainstem were collected. The CFA groups presented a mechanical hyperalgesia until day 21 (p ≤ 0.05). No differences were observed among groups in the HP (p = 0.735), and in the immobility and swimming time of the FS (p = 0.800; p = 0.998, respectively). In the brainstem, there was a significant difference in the TNF-ɑ levels (p = 0.043), and a marginal significant difference in BDNF levels (p = 0.054), without differences among groups in the hippocampal BDNF and TNF-ɑ levels (p = 0.232; p = 0.081, respectively). In conclusion, the hormone replacement therapy did not alleviate orofacial pain in ovariectomized rats. However, there is a decrease in brainstem TNF-ɑ levels in the animals submitted to both models, which was partially reverted by HRT.

Estrogen hormone therapy stabilizes lateral hairline in transfeminine patients: Implications for facial feminization surgery

BackgroundAlthough many studies report on the suppressing effects of estrogen therapy on facial and body hair in transgender and nonbinary (TGNB) individuals, few studies have elucidated its effects on hairline stability on the scalp. In this work, we assessed the influence of estrogen therapy on forehead length. MethodsAll TGNB patients assigned male at birth (AMAB) seeking facial feminization surgery aged 30 years or older were included in the study. Central and forehead length were collected at initial consultation visits. Variables that potentially influence hair growth were collected by chart review, including age, duration of hormone replacement therapy (HRT), presence of spironolactone, and presence of other hair treatments, including finasteride, dutasteride, or minoxidil. Multivariable linear regressions were constructed with relevant predictor variables, while also incorporating global health scores as a proxy for psychological effects on hair loss. Results171 patients were included in this study, with a median age of 36.0 [interquartile range (IQR): 32.0-46.0] years and a median HRT duration of 2.0 [1.0-6.0] years. Multivariable linear regressions revealed no significant predictors for central forehead length. On the other hand, lateral forehead length was positively predicted by age (B=0.06, 95% confidence interval (CI) [0.03-0.08], p<0.001) and hair treatment (B=0.66, 95%CI [0.14-1.18], p=0.01), but negatively predicted by HRT duration (B=-0.07, 95%CI [-0.10- -0.04], p<0.001). ConclusionsAlthough older age is a predictor of lateral hairline recession in TGNB AMAB individuals, lateral forehead length was also predicted to decrease by 0.07cm with each year of feminizing hormone therapy in patients over 30 years of age.

Commentary on “Oestrogen hormone therapy stabilizes lateral hairline in transfeminine patients: Implications for facial feminization surgery”

Commentary on “Oestrogen hormone therapy stabilizes lateral hairline in transfeminine patients: Implications for facial feminization surgery”

The Potentials of Phytoestrogen Compounds in Aquaculture – A Review

Abstract All organisms require the ability to engage in either sexual or asexual reproduction in order to ensure their own survival. In aquaculture, when one sex outgrows the other faster, farmers use hormones to stimulate growth. Furthermore, the production of fish based on sexual dimorphism is predominantly executed through the utilization of estrogens and androgens. Environmentally, these compounds may pollute the ecosystem and cause endocrine system alterations that cause harmful effects; thus, they must be handled carefully to assure environmental, biological, and food safety. Phytoestrogens as natural non-steroidal phenolic plant chemicals that resemble 17-β-estradiol, could be employed as a safe alternative source of natural estrogens. The phytoestrogens have many biological effects due to their ability to compete with estrogen receptors, but they may negatively affect fish production, reproduction, and behaviors under controlled conditions. Thus, the current literature emphasizes on the beneficial effects of phytoestrogens on aquatic animal performance, behaviors, and some reproductive features.

The Effect Flavonoids Phaleria macrocarpa Fruit Extract on Thickness of Trabeculae, Cortex Ratio Femoral Bone and Aortic Intima-Media in Mice Menopause Model

A deficiency of the hormone estrogen at menopause can lead to an increased rate of the destruction of the bone tissue that leads to bone loss, which can lead to osteoporosis and impaired fat metabolism, which increases the risk of atherosclerosis. Phytoestrogens from flavonoid extract P. Macrocarpa, having effects similar to endogenous estrogens themselves, prevent osteoporosis and atherosclerosis in menopausal women. The purpose of this research is to assess the influence of flavonoids from P. Macrocarpa fruit extract on trabeculae cortex thickness, ratio of femoral bone, and aortic IMT (A-IMT) in a menopausal mouse model. The study was conducted in a true experimental-posttest-only control group design. Using 32 mice; namely KN (normal mice with no treatment), KP (OVX with no treatment), P1(OVX and given flavonoid 3.75 mg/mice/day), P2 (OVX and given flavonoid 7.5 mg/mice/day), P3(OVX and given flavonoid 11.25 mg/mice/day), P4 (OVX and given flavonoid 15 mg/mice/day), the treatment given within 14 days. Then the thickness of the trabeculae, cortex, and intima-media aorta with Hematoxylin-Eosin (HE) staining. In the trabeculae, cortex thickness ratio obtained KN results meaningfully dissimilar to the KP group and the P3 and P4 groups were meaningfully dissimilar from the KP. The A-BMI in KP is meaningfully dissimilar to P1, P2, P3 and P4. The conclusion of the study is flavonoid fruit extract P. Macrocarpa can increase the thickness ratio of trabeculae, and cortex femoral bone of mice menopausal model in groups P3, P4 and can decrease A-IMT starting in groups P1 to P4.