Fetal gender prediction by monitoring circulating steroid hormones and some biochemical parameters in maternal dromedary camels.

To predict the sex of the foetus, healthy pregnant dromedary camels (n = 24) were included. Blood samples were collected for measurements of progesterone, estradiol, testosterone, and cortisol as well as total proteins, albumin, glucose, creatinine, blood urea nitrogen, phosphorus, calcium, creatine kinase, alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), calcium, phosphorus, and magnesium. Statistical analysis revealed differences between pregnant camels and pregnant camels in terms of female or male foetuses depending on the actual sex of the born calf. The results revealed that testosterone and ALP concentrations were significantly (P < 0.001) greater in camels given to males than in those given to calves. There were strong positive correlations between male calf birth and testosterone and ALP concentrations (r = 0.864; P < 0.0001 and r = 0.637; P < 0.001, respectively). On the other hand, the cortisol, glucose and creatinine concentrations were significantly lower (P lower in camel calved males than in females). There were significant negative correlations between male calf birth and the cortisol, glucose and creatinine concentrations (r =-0.401; P = 0.052; r =-0.445; P = 0.029 and r =-0.400; P = 0.053, respectively). The concentrations of calcium, phosphorus, calcium/phosphorus ratio, magnesium, and albumin and the albumin/globulin ratio were not significantly different (P > 0.05) between the two groups. In conclusion, testosterone could be used as a biomarker to determine the sex of foetuses in dromedary camels.

Effect of occupational exposure to vat-textile dyes on follicular and luteal hormones in female dye workers in Abeokuta, Nigeria.

Background: Some synthetic dyes used mainly in textile industries have been associated with endocrine disruption, resulting in infertility, among other disorders. It is unknown if occupational exposure to Vat textile dyes among premenopausal dyers alters hormonal levels. Objectives: We aimed at determining the probable effects of occupational exposure to Vat dyes on reproductive hormones of female textile dyers in the follicular and luteal phases while relating this to age categories and duration of exposure. Methods: Thirty-three premenopausal Vat textile dyers at "Itoku", Abeokuta, Nigeria, among a population of about 80 female dyers were age and sex-matched with 55 non-exposed (control) female participants. Using semi-structured questionnaires, socio-demographic, occupational details and the LMP of participants were obtained. Serum samples were collected in follicular and luteal phases and assayed for female sex hormones using Enzyme Immunoassay. Mann-Whitney U and Z- statistic were used for comparison of the two groups. P-value < 0.05 was considered to be significant. Results: In the follicular phase, the result showed a lower mean FSH ranking (in age category ≤20 years) and higher (p<0.05) Estradiol ranking (in age category 31-40 years) in the exposed than the unexposed. Mean ranks of Progesterone and Estradiol in the luteal phase (age category 31-40 years) were higher (p<0.05) in the exposed, while Estradiol (age category ≥41years) ranked lower (p<0.05). Prolactin demonstrated a significant inverse relationship with the duration of exposure. Conclusion: Occupational exposure to Vat dye among female dyers in Abeokuta is associated with some sex hormone disruption which appears to be age and duration of exposure-related.

Risk factors for empty follicle syndrome in diminished ovarian reserve patients undergoing intracytoplasmic sperm injection cycles: A retrospective observational analysis.

The aim of this study is to evaluate the risk factors for empty follicle syndrome (EFS) in patients with diminished ovarian reserve (DOR) undergoing an intracytoplasmic sperm injection cycle. In this retrospective study, patients with DOR were divided into 2 groups according to the presence of empty follicles on the day of oocyte retrieval. Patient age, body mass index (BMI), anti-Müllerian hormone (AMH), baseline follicle stimulating hormone (FSH) and estradiol (E2) levels, basal antral follicle count (AFC), total gonadotropin dose, and day of stimulation were recorded as risk factors. The association between EFS and these variables was assessed using the logistic regression method and ROC curve analysis. Increased BMI, low AMH, higher baseline FSH, low baseline AFC, higher gonadotropin dose, and longer day of ovulation induction were independent risk factors for EFS in patients with DOR. ROC curve analysis showed that BMI, AMH, baseline FSH, baseline AFC, higher gonadotropin dose, and longer ovulation induction days were predictive parameters in this group. According to the current study, higher BMI, lower AMH, higher baseline FSH, lower baseline AFC, higher gonadotropin dose and longer ovulation induction days were independent risk factors for EFS in patients with reduced ovarian reserve.

The natural menstrual cycle revisited - can natural cycle be trusted.

BACKGROUND: The serum progesterone (P4) level during the luteal phase (LP) plays a crucial role in the initiation and maintenance of pregnancy. However, it is unclear whether the natural cycle consistently provides the best endocrine profile and whether mid-luteal serum P4 levels are always sufficient to support implantation and early pregnancy. The question has become more relevant in relation to fertility treatment, as more frozen embryo transfer cycles are performed in the natural cycle. Moreover, can serum hormone levels and covariates measured during the follicular phase (FP), such as Follicle Stimulation Hormone (FSH), Luteinizing Hormone (LH), Estradiol (E2), Anti-Mullerian Hormone (AMH) and Antral Follicle Count (AFC), be used to predict P4 levels during the luteal phase (LP)? RESULTS: This observational prospective cohort study analysed 26 healthy women with a cycle length between 21-35 days and a body mass index (BMI) < 30 kg/m2. Blood sampling started on the fifth day of the menstrual cycle and continued every fifth day until the next cycle. The procedure was repeated for a total of three cycles. The study found that only ten women had a P4 level greater than 30 nmol/L on cycle day 20 or 25 in all three cycles. In total, only 45 cycles out of 77 cycles had serum P4 levels ≥ 30 nmol/L. The E2 level ≥ 345 pmol/L on cycle day 10 proved to be predictive of a P4 level of ≥ 30 nmol/L on either day 20 or day 25 with a sensitivity of 57% and a specificity of 89%. No other covariates, including the FSH level cycle day 5, LH levels during the follicular phase, age, weight, AFC and AMH cycle day 5 correlated with LP P4 levels. CONCLUSIONS: A significant correlation between FP E2 levels cycle day 5 (> 131pmol/L) and cycle day 10 (> 345pmol/L) and a LP P4 level ≥ 30 nmol/l was found; thus, the FP E2 level is a predictor of corpus luteum competence. Our findings highlight the existence of suboptimal P4 levels during the LP and a significant inter-individual and intra-cycle variation in P4 levels during the LP in regular menstruating women.

Greater sensitivity of the circadian system of women to bright light, but not dim-to-moderate light.

Women typically sleep and wake earlier than men and have been shown to have earlier circadian timing relative to the light/dark cycle that synchronizes the clock. A potential mechanism for earlier timing in women is an altered response of the circadian system to evening light. We characterized individual-level dose-response curves for light-induced melatonin suppression using a within-subjects protocol. Fifty-six participants (29 women, 27 men; aged 18-30 years) were exposed to a range of light illuminances (10, 30, 50, 100, 200, 400, and 2000 lux) using melatonin suppression relative to a dim control (<1 lux) as a marker of light sensitivity. Women were free from hormonal contraception. To examine the potential influence of sex hormones, estradiol and progesterone was examined in women and testosterone was examined in a subset of men. Menstrual phase was monitored using self-reports and estradiol and progesterone levels. Women exhibited significantly greater melatonin suppression than men under the 400-lux and 2000-lux conditions, but not under lower light conditions (10-200 lux). Light sensitivity did not differ by menstrual phase, nor was it associated with levels of estradiol, progesterone, or testosterone, suggesting the sex differences in light sensitivity were not acutely driven by circulating levels of sex hormones. These results suggest that sex differences in circadian timing are not due to differences in the response to dim/moderate light exposures typically experienced in the evening. The finding of increased bright light sensitivity in women suggests that sex differences in circadian timing could plausibly instead be driven by a greater sensitivity to phase-advancing effects of bright morning light.

Silkworm (Bombyx mori L.) Has Beneficial Effects on Menopausal Symptoms by Enhancing Estrogen Receptor Signaling in Ovariectomized Mice.

Existing hormone replacement therapy for menopause has drawbacks, necessitating new treatment agents. Silkworms have demonstrated estrogenic properties, offering promising alternatives. We assessed the therapeutic effects of freeze-dried silkworm powder (SWP) on menopausal symptoms using an ovariectomized (OVX) mouse model. The experimental design comprised a sham surgery group (Sham), an OVX control group, a low-dose SWP group post-OVX (80 mg/kg, OVX-SWP-L), a high-dose SWP group post-OVX (160 mg/kg, OVX-SWP-H), and an estradiol treatment group post-OVX (OVX-E2). Treatments were administered orally thrice weekly over eight weeks; body weight was monitored weekly. The SWP-treated groups (SWP-L and SWP-H) exhibited less weight gain and increased uterine thickness than the OVX control. Molecular analyses demonstrated that SWP significantly enhanced the phosphorylation of estrogen receptor alpha (ERα), ERK, and AKT. Furthermore, biochemical assays revealed reduced serum neutral lipids across all SWP treatment groups. Notably, HDL-cholesterol levels were significantly increased in the SWP-L group compared to the OVX group. Serum estradiol concentrations were elevated in all the SWP groups, with significant increases in the high-dose group. These findings indicate that SWP may promote the activation of estrogen receptor signaling and improve symptoms associated with estrogen deficiency during menopause.

Pharmacokinetics and Safety of Estradiol Valerate Tablet and Its Generic: A Phase 1 Bioequivalence Study in Healthy Chinese Postmenopausal Female Subjects.

Purpose: Estradiol valerate (Progynova®) is used as hormone therapy to supplement estrogen deficiency. This study aimed to assess the bioequivalence of an estradiol valerate tablet and its generic form, under fasting and fed conditions. Methods: A randomized, open-label, single-dose, 2-period crossover study was conducted on healthy postmenopausal Chinese female volunteers under fasting and fed conditions. For each period, the subjects received either a 1 mg tablet of estradiol valerate or its generic. Blood samples were collected before dosing and up to 72 hours after administration. Plasma levels of total estrone, estradiol, and unconjugated estrone were quantified using a validated liquid chromatography-tandem mass spectrometry method. Results: A total of 54 volunteers were enrolled in this study. The primary pharmacokinetic parameters, including Cmax, AUC0-t, and AUC0-∞, were similar for the two drugs under both fasting and fed conditions, with 90% confidence intervals for the geometric mean ratios of these parameters, all meeting the bioequivalence criterion of 80-125%. A total of 48 adverse events (AEs) were reported in the fed study compared with 24 AEs in the fasting study. Conclusion: Estradiol valerate and its generic form were bioequivalent and well tolerated under both fasting and fed conditions.

The usefulness of peri-trigger female reproductive hormones (delta-FRH) in predicting oocyte maturation in normal ovarian reserve patients who received in vitro fertilization-embryo transfer: a retrospective study.

Objectives: To evaluate the efficacy of peri-trigger female reproductive hormones (FRHs) in the prediction of oocyte maturation in normal ovarian reserve patients during the in vitro fertilization-embryo transfer (IVF-ET) procedure. Materials and Methods: A hospital database was used to extract data on IVF-ET cases from January 2020 to September 2021. The levels of female reproductive hormones, including estradiol (E2), luteinizing hormone (LH), progesterone (P), and follicle-stimulating hormone (FSH), were initially evaluated at baseline, the day of the trigger, the day after the trigger, and the day of oocyte retrieval. The relative change in E2, LH, P, FSH between time point 1 (the day of trigger and baseline) and time point 2 (the day after the trigger and day on the trigger) was defined as E2_RoV1/2, LH_RoV1/2, P_RoV1/2, and FSH_RoV1/2, respectively. Univariable and multivariable regression were performed to screen the peri-trigger FRHs for the prediction of oocyte maturation. Results: A total of 118 patients were enrolled in our study. Univariable analysis revealed significant associations between E2_RoV1 and the rate of MII oocytes in the GnRH-agonist protocol group (p < 0.05), but not in the GnRH-antagonist protocol group. Conversely, P_RoV2 emerged as a potential predictor for the rate of MII oocytes in both protocol groups (p < 0.05). Multivariable analysis confirmed the significance of P_RoV2 in predicting oocyte maturation rate in both groups (p < 0.05), while the association of E2_RoV1 was not significant in either group. However, within the subgroup of high P_RoV2 in the GnRH-agonist protocol group, association was not observed to be significant. The C-index was 0.83 (95% CI [0.73-0.92]) for the GnRH-agonist protocol group and 0.77 (95% CI [0.63-0.90]) for the GnRH-antagonist protocol group. The ROC curve analysis further supported the satisfactory performance of the models, with area under the curve (AUC) values of 0.79 for the GnRH-agonist protocol group and 0.81 for the GnRH-antagonist protocol group. Conclusions: P_RoV2 showed significant predictive value for oocyte maturation in both GnRH-agonist and GnRH-antagonist protocol groups, which enhances the understanding of evaluating oocyte maturation and inform individualized treatment protocols in controlled ovarian hyperstimulation during IVF-ET for normal ovarian reserve patients.

Decoding connections in the European population: serum uric acid, sex hormone-binding globulin, total testosterone, estradiol, and female infertility - advanced bidirectional and mediative Mendelian randomization.

Background: Despite observational links between serum uric acid (SUA), sex hormone-related phenotypes, and female infertility, the causality behind these associations remains uncertain. Objective: This study utilizes Bidirectional Two-Sample and Mediation Mendelian Randomization to explore the causal relationships and mediation effects of sex hormone-binding globulin (SHBG), total testosterone (TT), and estradiol on these associations. Methods: We analyzed single-nucleotide polymorphisms (SNPs) associated with SUA and sex hormone levels using data from large-scale GWAS of European populations. Female infertility data were sourced from 6,481 cases and 75,450 controls in the FinnGen Consortium. We employed methods including Inverse Variance Weighted (IVW), Weighted Median, and MR-Egger regression to assess causality. Results: We found that elevated SUA levels causally increase the risk of female infertility (IVW OR: 1.13, P=0.047). Elevated SUA levels significantly decrease SHBG levels (ß=-0.261; P=2.177e-04), with SHBG mediating 27.93% of the effect of SUA on infertility (OR=0.854; 95%CI, 0.793-0.920; P=2.853e-05). Additionally, elevated TT levels, which were associated with decreased SUA levels (ß=-0.127), showed an indirect effect on infertility mediated by SUA (ß=-0.0187; 95% CI, -0.041 to -0.003; P=0.046). Conclusion: Our findings demonstrate causal links between high SUA and increased risk of female infertility mediated by hormonal factors such as SHBG and TT. These insights suggest new avenues for infertility treatment and highlight the need for further research into these mechanisms.

Levels of Sex Hormones and Abdominal Muscle Composition in Men from The Multi-Ethnic Study of Atherosclerosis.

Information on the associations of testosterone levels with abdominal muscle volume and density in men is limited, while the role of estradiol and SHBG on these muscle characteristics are unclear. Therefore, this study aimed to investigate the association between fasting serum sex hormones and CT-derived abdominal muscle area and radiodensity in adult men. Conducted as a cross sectional observational study using data from the Multi-Ethnic Study of Atherosclerosis, our analyses focused on a community-based sample of 907 men aged 45-84 years, with 878 men having complete data. CT scans of the abdomen were interrogated for muscle characteristics, and multivariable linear regressions were used to test the associations. After adjustment for relevant factors, higher levels of both total testosterone and estradiol were associated with higher abdominal muscle area (1.74, 0.1-3.4, and 1.84, 0.4-3.3, respectively). In the final analyses, levels of total testosterone showed a positive association, while an inverse relationship was observed for SHBG with abdominal muscle radiodensity (0.3, 0.0-0.6, and - 0.33, - 0.6 to - 0.1, respectively). Our results indicate a complex association between sex hormones and abdominal muscle characteristics in men. Specifically, total testosterone and estradiol were associated with abdominal muscle area, while only total testosterone was associated with muscle radiodensity and SHBG was inversely associated with muscle radiodensity.Clinical Trial: NCT00005487.

Menstrual cycle-driven hormone concentrations co-fluctuate with white and gray matter architecture changes across the whole brain.

Cyclic fluctuations in hypothalamic-pituitary-gonadal axis (HPG-axis) hormones exert powerful behavioral, structural, and functional effects through actions on the mammalian central nervous system. Yet, very little is known about how these fluctuations alter the structural nodes and information highways of the human brain. In a study of 30 naturally cycling women, we employed multidimensional diffusion and T1-weighted imaging during three estimated menstrual cycle phases (menses, ovulation, and mid-luteal) to investigate whether HPG-axis hormone concentrations co-fluctuate with alterations in white matter (WM) microstructure, cortical thickness (CT), and brain volume. Across the whole brain, 17ß-estradiol and luteinizing hormone (LH) concentrations were directly proportional to diffusion anisotropy (µFA; 17ß-estradiol: ß1 = 0.145, highest density interval (HDI) = [0.211, 0.4]; LH: ß1 = 0.111, HDI = [0.157, 0.364]), while follicle-stimulating hormone (FSH) was directly proportional to CT (ß1 = 0 .162, HDI = [0.115, 0.678]). Within several individual regions, FSH and progesterone demonstrated opposing relationships with mean diffusivity (Diso) and CT. These regions mainly reside within the temporal and occipital lobes, with functional implications for the limbic and visual systems. Finally, progesterone was associated with increased tissue (ß1 = 0.66, HDI = [0.607, 15.845]) and decreased cerebrospinal fluid (CSF; ß1 = -0.749, HDI = [-11.604, -0.903]) volumes, with total brain volume remaining unchanged. These results are the first to report simultaneous brain-wide changes in human WM microstructure and CT coinciding with menstrual cycle-driven hormone rhythms. Effects were observed in both classically known HPG-axis receptor-dense regions (medial temporal lobe, prefrontal cortex) and in other regions located across frontal, occipital, temporal, and parietal lobes. Our results suggest that HPG-axis hormone fluctuations may have significant structural impacts across the entire brain.

Sex-Specific Differences in Serum Kallikrein-8 (KLK8): An Exploratory Study.

Background: There are indications for sex-specific differences regarding the association between kallikrein-8 (KLK8) and cognitive impairment in early stages of Alzheimer's disease for which KLK8 may be an early blood-based biomarker. These may be due to different levels of sex hormones. To correctly interpret KLK8 blood concentrations, sex-specific analyses are needed. Objective: The aim of our exploratory study was to investigate sex-specific differences in blood-based KLK8 in participants of the population-based Heinz Nixdorf Recall study with different cognitive status and the association between KLK8 and sex hormones. Methods: In 290 participants (45% women, 69.7±7.4 years (mean±SD)) we investigated sex-specific serum KLK8 differences between cognitively unimpaired (CU, 43%) and cognitively impaired (CI) participants and the association between KLK8 and dehydroepiandrosteronsulfate (DHEAS), estradiol and testosterone, using adjusted multiple linear regression. Results: The mean±SD KLK8 was similar for CU men (808.1±729.6 pg/ml) and women (795.9±577.7 pg/ml); adjusted mean-difference [95%-CI]: -95.3 [-324.1;133.5] pg/ml. KLK8 was lower in CI women (783.5±498.7 pg/ml) than men (1048.4±829 pg/ml); -261 [-493.1; -29] pg/ml. In men but not women, there was a weak indication for a positive slope between estradiol (11.9 [-0.4;24.3] pg/ml) and DHEAS (1.4 [-0.5;3.3] pg/ml) with KLK8, while testosterone had no impact. Conclusions: The results suggested a different role for KLK8 in the development of cognitive impairment in men and women, potentially influenced by sex hormones. To use blood KLK8 as an early biomarker, further research on hormonal regulation of KLK8 expression is needed as a part of the investigation of the KLK8 involvement in cognitive impairment and Alzheimer's disease pathology.

Blood Sampling and Hormone Measurement for Determining the Stage in the Ovarian Cycle in Marmosets.

Common marmosets are small New World monkeys. Since many of their biological mechanisms are similar to those of humans, marmosets are potentially useful for medical and human biology research across a range of fields, such as neuroscience, regenerative medicine, and development. However, there is a lack of literature describing methods for many basic experiments and procedures. Here, detailed methods for determining the levels of sex hormones (progesterone, estradiol, and chorionic gonadotropin) in marmosets are described. The measurement of these hormones enables the prediction of the stage in the ovarian cycle, which is typically 26-30 days in marmosets; accurate determination is essential for the harvesting of oocytes/zygotes at the correct time point and for the preparation of host females for the generation of genetically modified marmosets. Additionally, the measurement of sex hormone levels is useful for endocrinology, ethology, early development, and reproductive biology studies. This protocol provides a detailed description of the methods for blood sampling from the femoral vein, separation of plasma for hormone measurement, measuring chorionic gonadotropin levels using urine and plasma, resetting the ovarian cycle using injections of a prostaglandin F2α analog to shorten and synchronize the cycle, and promoting follicular growth and ovulation by injecting follicle-stimulating hormone and chorionic gonadotropin. Using these protocols, the stages in the ovarian cycle can be determined for the timely collection of oocytes/zygotes.

Gender-Affirming Hormone Treatment and Metabolic Syndrome Among Transgender Veterans.

Importance: Gender-affirming hormone treatment (GAHT) is a common therapy for transgender individuals to reduce gender dysphoria and improve quality of life. Clarifying the long-term effects of GAHT remains a priority in transgender health research. Objective: To explore whether sex hormones (estradiol and testosterone) are associated with the development of metabolic syndrome in transgender veterans compared with cisgender veterans. Design, Setting, and Participants: This retrospective, longitudinal cohort study used International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes for gender dysphoria from the Veterans Health Administration national database to identify transfeminine and transmasculine veterans receiving documented feminizing (estradiol) or masculinizing (testosterone) treatment from January 1, 2006, to December 31, 2019, and for whom the GAHT initiation date and metabolic syndrome component-related data were available. Transgender veterans were matched to cisgender referents. Exposure: Gender-affirming hormone treatment. Main Outcomes and Measures: Metabolic syndrome z-scores were calculated based on body mass index, systolic blood pressure, and levels of high-density lipoprotein cholesterol, triglycerides, and blood glucose. Changes in mean z-scores were compared among the transgender and cisgender groups before and after the index date (corresponding to GAHT initiation) using a repeated-measures analysis of variance model. Results: The cohort included 1290 participants: 645 transgender (494 [38.3%] transfeminine, 151 [11.7%] transmasculine) and 645 cisgender (280 [21.7%] female, 365 [28.3%] male). Mean (SD) age at the index date was 41.3 (13.2) years. Metabolic syndrome z-scores changed significantly over time and differed significantly across groups. Overall, transmasculine veterans had the greatest percentage increase in mean (SEM) z-scores after vs before the index date (298.0% [57.0%]; P < .001), followed by cisgender females (108.3% [27.5%]; P < .001), cisgender males (49.3% [27.5%]; P = .02), and transfeminine persons (3.0% [10.7%]; P = .77). Conclusions and Relevance: In this cohort study, in both cisgender and transgender veterans, estradiol was associated with reduced metabolic syndrome risk, whereas testosterone was associated with increased risk. However, transmasculine individuals had the greatest risk and transfeminine individuals had the lowest risk of metabolic syndrome associated with these hormones. This is relevant for the management of metabolic syndrome risk factors in cisgender and transgender individuals and to potentially predict the risk of atherosclerotic cardiovascular disease, type 2 diabetes, systolic hypertension, insulin resistance, and nonalcoholic fatty liver disease.

The relationship between follicle-stimulating hormone and metabolic dysfunction-associated fatty liver disease in men.

OBJECTIVES: The present study aimed to investigate the relationship between male hormones and metabolic dysfunction-associated fatty liver disease (MAFLD) in males. METHODS: Data from the Fangchenggang Area Male Health and Examination Survey (FAMHES) were used to analyze the male hormone levels between MAFLD patients and controls. Univariate and multivariate logistic regression analyses were performed to identify risk factors for MAFLD. Receiver operating characteristic curve analysis was used to assess the diagnostic performance of male hormones for MAFLD. RESULT: A total of 1578 individuals were included, with 482 individuals (30.54%) of MAFLD, including 293 (18.57%) with mild disease and 189 (11.98%) with moderate-to-severe disease. The MAFLD patients were significantly older than those without MAFLD. The LH, FSH, and SHBG levels in the MAFLD patients were significantly greater than those in the control group. Age, FSH, LH, SHBG, and estradiol were all risk factors for MAFLD. Age, FSH, and LH were risk factors for moderate-to-severe MAFLD. FSH was an independent risk factor for MAFLD and moderate-to-severe MAFLD. FSH showed an excellent diagnostic value, with an AUC of 0.992 alone and 0.996 after adjusting age. CONCLUSIONS: Our findings indicate that FSH may be a potential diagnostic and predictive biomarker for MAFLD.

Estrogen deprivation and estrogen receptor α antagonism decrease DSS colitis in female mice.

The association of hormonal contraception with increased risk of inflammatory bowel disease (IBD) observed in females suggests involvement of ovarian hormones, such as estradiol, and the estrogen receptors in the progression of intestinal inflammation. Here, we investigated the effects of prophylactic SERM2 and estradiol supplementation in dextran sulfate sodium-induced colitis using mice with intact ovaries and ovariectomized (OVX) female mice. We found that graded colitis score was threefold reduced in the OVX mice, compared to mice with intact ovaries. Estradiol supplementation, however, aggravated the colitis in OVX mice, increasing the colitis score to a similar level than what was observed in the intact mice. Further, we observed that immune infiltration and gene expression of inflammatory interleukins Il1b, Il6, and Il17a were up to 200-fold increased in estradiol supplemented OVX colitis mice, while a mild but consistent decrease was observed by SERM2 treatment in intact animals. Additionally, cyclo-oxygenase 2 induction was increased in the colon of colitis mice, in correlation with increased serum estradiol levels. Measured antagonist properties of SERM2, together with the other results presented here, indicates an exaggerating role of ERα signaling in colitis. Our results contribute to the knowledge of ovarian hormone effects in colitis and encourage further research on the potential use of ER antagonists in the colon, in order to alleviate inflammation.

The GG genotype of rs743572 in CYP17A1 gene regulating the decrease of T/E ratio can be an independent risk factor for MetS-BPH: a retrospective cohort study.

PURPOSE: To confirm if the CYP17A1 gene regulates the ratio of T/E leading to MetS-BPH. METHODS: 824 men, aged 47-88 years, were recruited into this study through consecutive routine physical examination programs and long-term outpatient screening. Several parameters, including SNPs of CYP17A1 gene, total testosterone, estradiol, and the ratio of total testosterone to estradiol (T/E) were obtained for each participant. Based on the diagnosis of BPH, MetS, and MetS-BPH, the participants were divided into BPH and non-BPH groups, MetS and non-MetS groups, and MetS-BPH and non-MetS-BPH groups. Values of the obtained parameters were evaluated using one-way analysis of variance, Student's t-test, Chi-squared test, and logistic regression analysis. RESULTS: SNPs of the CYP17A1 gene, including the rs743572 genotypes (GG, GA, and AA), rs3781287 genotypes (GG, GT, TT), and rs4919686 genotypes (CC, CA, and AA), were present in every group. Only the GG genotype of rs743572 was independently associated with BPH (OR = 5.868, 95% CI: 3.363-7.974, P < 0.001), MetS (OR = 7.228, 95% CI: 3.925-11.331, P < 0.001), and MetS-BPH (OR = 3.417, 95% CI: 1.783-5.266, P < 0.001) after adjusting for age. In the population of genotype GG of rs743572, the decrease in T/E ratio was an independent risk factor for BPH (OR = 839.756, 95% CI: 36.978-1334.263, P = 0.001), MetS (OR = 376.988, 95% CI: 12.980-488.976, P < 0.003), and MetS-BPH (OR = 388.236, 95% CI: 24.869-495.363, P = 0.003). CONCLUSION: The GG genotype of rs743572 in CYP17A1 gene regulating the decrease of T/E ratio can be an independent risk factor for MetS-BPH populations. TRIAL REGISTRATION NUMBER: ChiCTR2200057632 "retrospectively registered". DATE OF REGISTRATION: March 15, 2022 "retrospectively registered".

Association between systemic immunity-inflammation index and sex hormones in children and adolescents aged 6-19.

Objectives: This study aimed to evaluate the relationship between systemic immune-inflammation index (SII) and sex hormones in children and adolescents aged 6-19 years. Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2016. Inclusion criteria comprised subjects aged 6-19 years with complete data on both SII and sex hormones. We employed weighted multiple regression analysis and subgroup analytical methods to independently estimate the relationship between SII and sex hormones. Results: In this study, a total of 3767 participants were included, with an average age of 12.32 ± 3.95 years. Males constituted 50.54%, and females 49.46%. Among males, a statistically significant negative correlation emerged between SII and sex hormone-binding globulin (SHBG). Similarly, in the female population, SII exhibited a statistically significant negative correlation with total testosterone (TT), SHBG, and the Ratio of TT to estradiol, while maintaining a positive correlation with free androgen index (FAI). Subgroup analysis underscored variances in the association between sex hormones and SII within cohorts distinguished by pubertal status or different body mass index (BMI). In addition, the relationship between SII and estradiol exhibited nonlinearity. Employing a two-segment linear regression model, we identified an inverted U-shaped association between SII and estradiol, with an inflection point of 748.09 (1000cell/ml). Conclusion: Our findings suggest that SII may be an independent risk factor for changes in sex hormones in both male and female children and adolescents. More prospective and experimental studies should be conducted to validate our results and elucidate the underlying molecular pathways.

Proliferation and apoptosis dynamics of the normal canine mammary gland during the oestrous cycle evaluated by Ki-67 and Caspase-3 indexes.

Understanding the normal physiology of the canine mammary gland (CMG) is crucial, as it provides a foundational reference for understanding canine mammary neoplasms. The relation between the Proliferation Index (PI) indicated by Ki-67 expression, along with the Apoptotic Index (AI) determined through Caspase-3 expression during the oestrous cycle, is inadequately documented in existing literature. This study seeks to offer insights into the interplay between PI and AI in the CMG across oestrous cycle phases. An extensive investigation was conducted on a diverse case series of bitches (n = 18). Oestrous cycle stages were determined through vaginal cytology, histological examination of the reproductive tract and serum progesterone and oestradiol concentrations. The entire mammary chain was histologically examined, and proliferation and apoptosis were assessed via double immunohistochemistry employing anti-Ki-67 and Caspase-3 antibodies. PI and AI were evaluated through a systematic random sampling approach, counting a minimum of 200 cells for each cell type. There was a significantly higher PI during early dioestrus in all mammary gland components, with a greater proportion of positive cells observed in epithelial cells compared to stromal cells. The highest PI was detected in epithelial cells within the end buds. Significant differences were found in Ki-67 labelling across the cranial mammary glands. A positive and strong correlation was noted between progesterone concentration and PI in epithelial cells. The AI remained consistently low throughout the oestrous cycle, with few differences observed across histological components. Caspase-3 labelling displayed the highest positivity in caudal mammary pairs. A negative and moderate correlation was identified between progesterone concentration and AI in interlobular mesenchymal cells. This study highlights the influence of endocrine regulation on cell proliferation indices in mammary tissue, emphasizing the need to consider these hormonal variations in toxicopathological studies involving canine mammary gland.

Associations between mycoestrogen exposure and sex steroid hormone concentrations in maternal serum and cord blood in the UPSIDE pregnancy cohort.

Zearalenone (ZEN) is a fungal-derived toxin found in global food supplies including cereal grains and processed foods, impacting populations worldwide through diet. Because the chemical structure of ZEN and metabolites closely resembles 17ß-estradiol (E2), they interact with estrogen receptors α/ß earning their designation as 'mycoestrogens'. In animal models, gestational exposure to mycoestrogens disrupts estrogen activity and impairs fetal growth. Here, our objective was to evaluate relationships between mycoestrogen exposure and sex steroid hormone concentrations in maternal circulation and cord blood for the first time in humans. In each trimester, pregnant participants in the UPSIDE study (n = 297) provided urine for mycoestrogen analysis and serum for hormone analysis. At birth, placental mycoestrogens and cord steroids were measured. We fitted longitudinal models examining log-transformed mycoestrogen concentrations in relation to log-transformed hormones, adjusting for covariates. Secondarily, multivariable linear models examined associations at each time point (1st, 2nd, 3rd trimesters, delivery). We additionally considered effect modification by fetal sex. ZEN and its metabolite, α-zearalenol (α-ZOL), were detected in >93% and >75% of urine samples; >80% of placentas had detectable mycoestrogens. Longitudinal models from the full cohort exhibited few significant associations. In sex-stratified analyses, in pregnancies with male fetuses, estrone (E1) and free testosterone (fT) were inversely associated with ZEN (E1 %Δ: -6.68 95%CI: -12.34, -0.65; fT %Δ: -3.22 95%CI: -5.68, -0.70); while α-ZOL was positively associated with E2 (%Δ: 5.61 95%CI: -1.54, 9.85) in pregnancies with female fetuses. In analysis with cord hormones, urinary mycoestrogens were inversely associated with androstenedione (%Δ: 9.15 95%CI: 14.64, -3.30) in both sexes, and placental mycoestrogens were positively associated with cord fT (%Δ: 37.13, 95%CI: 4.86, 79.34) amongst male offspring. Findings support the hypothesis that mycoestrogens act as endocrine disruptors in humans, as in animal models and livestock. Additional work is needed to understand impacts on maternal and child health.