Steroid Levels Research Articles

Biodistribution of synthesized polyethylene terephthalate fibers in adult zebrafish, their sex hormone disruption effect, and mitigation using natural organic matter

Although polyethylene terephthalate (PET) fibers are a representative form of plastic pollutants, studies on their toxicity are currently limited compared to other plastic types. Moreover, the effect of natural organic matter (NOM) on their toxicity has not been investigated. In this study, female and male adult zebrafish were exposed to synthesized PET fibers at concentrations of 0.1, 1, 10, and 100 mg/L in the presence and absence of 10 mg/L of NOM for 10 d. Bioaccumulation of PET fibers in zebrafish intestine, liver, and gills was identified and expression levels of reactive oxygen species (ROS) generation, sex hormones, and oxidative stress and sex hormone-related genes were measured. In addition, the developmental stages of gonadal cells were examined through histological analysis. We found that PET fibers bioaccumulated in the intestine and liver of zebrafish. ROS generation significantly increased at 100 mg/L of PET fibers, the expression of oxidative stress-related genes decreased in female and increased in male zebrafish. Exposure to 100 mg/L of PET fibers did not affect 17-beta estradiol, but significantly decreased the testosterone levels in male zebrafish. Sex hormone-related genes significantly decreased in both female and male zebrafish, except for androgen receptor in female zebrafish. However, these changes were exacerbated by the removal of NOM, suggesting a protective effect of NOM against PET fibers toxicity. We demonstrated that the accumulated PET fibers may lead to oxidative stress and sex hormone alteration, and disrupt the development of gonadal cells. Additionally, the NOM coating did not alter bioaccumulation considerably, but mitigated the adverse effects at the hormone level in PET fiber-exposed zebrafish. Thus, this study provides a basis for further research on the toxicity assessment of PET fibers and interactions between NOM and PET fiber-related toxicity.

The Antioxidant Activity of Atomized Extracts of the Leaves and Stems of Cnidoscolus diacanthus (Pax & K. Hoffm.) J.F. Macbr. from Peru and Their Effect on Sex Hormone Levels in Rats

In this research, we aimed to determine the antioxidant activity of an atomized extract of Cnidoscolus diacanthus (Pax & K. Hoffm.) J.F. Macbr., known in Peru as “huanarpo hembra”, and its effect on sex hormone levels. Its phytochemical profile was determined using liquid chromatography–mass spectrometry (LC–MS), while its total phenol content (TPC) and total flavonoids (TFs) were determined using the Folin–Ciocalteu method and the aluminum chloride method. Its antioxidant activity was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH), the radical 2,2-azino-bis-3-ethylbenzthiazolin-6 sulfonic acid (ABTS), and ferric-reducing antioxidant power (FRAP). The biological activity of C. diacanthus and its effect on sexual hormones were determined in Holtzman rats of both sexes. Phytochemical analysis revealed the presence of flavonoids and phenolic compounds in its leaves and stems, mainly rutin, quercetin, chlorogenic acid, and genistein. However, the stem extract contained higher total phenol (464.38 ± 4.40 GAE/g) and flavonoid (369.17 ± 3.16 mg QE/g of extract) contents than the leaf extract (212.38 ± 3.19 mg GAE/g and 121.49 ± 2.69 mg QE/g). For DPPH, ABTS, and FRAP, the Trolox-equivalent antioxidant capacity (TEAC) was 597.20 ± 5.40 µmol/g, 452.67 ± 5.76 µmol/g, and 535.91 ± 1.56 µmol/g, respectively, for the stems, while for the leaves, it was 462.39 ± 3.99 µmol/g, 202.32 ± 5.20 µmol/g, and 198.13 ± 1.44 µmol/g, respectively. In terms of the values for hormonal levels, at a dose of 100 mg/kg of the extract, testosterone levels of 1.430 ng/mL (with the leaf extract) and 1.433 ng/mL (with the stem extract), respectively, were found in the male rats. Regarding estradiol levels, in the female rats, these were 10.425 ng/mL (leaf extract) and 8.775 ng/mL (stem extract), while their levels of luteinizing hormone were 0.320 mIU/mL (leaf extract) and 0.273 mIU/mL (stem extract). For the follicle-stimulating hormone, levels of 0.858 mIU/mL (leaf extract) and 0.840 mIU/mL (stem extract) were found in the female rats, and levels of 0.220 mIU/mL (leaf extract) and 0.200 mIU/mL (stem extract) were found in the male rats. It is concluded that the C. diacanthus stem extract had a greater antioxidant capacity than the leaf extract, while both extracts had a superior effect on the sex hormone levels in the female rats compared to the male rats.

Minor changes to circulating steroid hormones in female rats after perinatal exposure to diethylstilbestrol or ketoconazole

Current chemical test strategies lack sensitive markers for detecting female reproductive toxicity caused by endocrine disrupting chemicals (EDCs). In search of a potentially sensitive readout, the steroidogenic disrupting effects of the well-known EDCs ketoconazole (KTZ) and diethylstilbestrol (DES) were investigated in vitro and on circulating steroid hormones in perinatally exposed female Sprague-Dawley rats. Twenty-one steroid hormones were analysed using LC-MS/MS in plasma from female rat offspring at postnatal day (PD) 6, 14, 22, 42 and 90. Most circulating steroid hormone levels increased with age except for estrone (E1), estradiol (E2) and backdoor pathway androsterone (ANDROST), which decreased after PD 22. Perinatal exposure to DES did not affect circulating steroid hormone levels at any dose or age compared to controls. KTZ exposure resulted in dose-dependent increase of corticosterone (CORTICO) at PD 6 and PD 14, with statistical significance only at PD 14. In the in vitro gold standard H295R steroidogenesis assay, twenty-one steroid hormones were measured instead of only T and E2. DES had subtle effects on steroidogenesis, whereas KTZ decreased most steroid hormones, but increased CORTICO, progesterone (P4), estriol (E3) initially (around 0.1–1 µM) before decreasing. Our data suggests that circulating steroidomic profiling may not be a sensitive readout for EDC-induced female reproductive toxicity. Further studies are needed to associate H295R assay steroidomic profiles with in vivo profiles, especially in target tissues such as adrenals or gonads. Expanding the H295R steroidogenic assay to include a comprehensive steroidomic profile may enhance its regulatory applicability.

Correlation Between Sex Hormones (Testosterone and Prolactin) and Anti-ds-DNA Antibody Levels in Systemic Lupus Erythematosus Patients: A Gender-Specific Analysis of the Hormonal Influence on Immune Responses.

Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that mostly affects women and has a noteworthy gender gap. Although the precise effects of sex hormones on SLE are yet unknown, they may modulate the immune response and affect the severity of the illness. Two important sex hormones that have apossible influence on autoimmune processes are prolactin and testosterone. The objective of this study was to assess the correlation between the levels of different sex hormones (testosterone and prolactin) and anti-double-stranded DNA (anti-ds-DNA) antibody levels in Sudanese anti-ds-DNA-positive SLE patients. Methodology A prospective cross-sectional study was conducted from February to July 2017 at Al-Rayan Specialized Medical Laboratory Complex and Omdurman Military Hospital, Sudan. There were 90 SLE patients who tested positive for anti-ds-DNA. Using commercial kits, serum levels of prolactin, testosterone, and anti-ds-DNA antibodies were tested from blood samples. SPSS version 21 was used for statistical analysis to find relationships between hormone levels and antibody levels. Results In this study of 90 patients with SLE, gender distribution was 14 males (16%) and 76 females (84%). The mean prolactin levels were significantly higher in males (17.99 ng/ml) compared to females (15.73 ng/ml, P < 0.001), and testosterone levels were also significantly higher in males (1.43 ng/ml) than females (0.37 ng/ml, P = 0.001). Although males had slightly higher mean levels of anti-ds-DNA antibodies (4.51) compared to females (4.08), this difference was not statistically significant. The results of correlation analyses indicated a weak and non-significant link between anti-ds-DNA antibody levels and hormone levels, with prolactin's Spearman's rho value of -0.054 (P = 0.616) and testosterone's Spearman's rho value of 0.080 (P = 0.456). Conclusion It was found that prolactin and testosterone levels differ by gender in SLE patients and that these hormones may have an impact on how the condition is managed. But the poor associations with anti-ds-DNA antibody levels suggest that further investigation is required to fully comprehend these intricate interactions.

Supraphysiological Dose of Testosterone Impairs the Expression and Distribution of Sex Steroid Receptors during Endometrial Receptivity Development in Female Sprague-Dawley Rats.

This study aims to investigate the effect of a supraphysiological dose of testosterone on the levels of sex steroid hormones and the expression and distribution of sex steroid receptors in the uterus during the endometrial receptivity development period. In this study, adult female Sprague-Dawley rats (n = 24) were subcutaneously administered 1 mg/kg/day of testosterone alone or in combination with the inhibitors (finasteride or anastrozole or both) from day 1 to day 3 post-coitus, while a group of six untreated rats served as a control group. The rats were sacrificed on the evening of post-coital day 4 of to measure sex steroid hormone levels by ELISA. Meanwhile, gene expression and protein distribution of sex steroid receptors were analysed by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC), respectively. In this study, treatment with a supraphysiological dose of testosterone led to a significant reduction in oestrogen and progesterone levels compared to the control. The mRNA expression of the androgen receptor increased significantly in all treatment groups, while the mRNA expression of both the progesterone receptor and the oestrogen receptor-α decreased significantly in all treatment groups. The IHC findings of all sex steroid receptors were coherent with all mRNAs involved. This study shows that a supraphysiological dose of testosterone was able to interrupt the short period of the implantation window. This finding could serve as a basis for understanding the role of testosterone in endometrial receptivity in order to develop further therapeutic approaches targeting androgen-mediated disorders of endometrial receptivity.

The long-term effects of norgestrel on the reproductive and thyroid systems in adult zebrafish at environmentally relevant concentrations

Progestins are crucial steroid hormones that have attracted wide attention due to their endocrine disrupting effects in fish. The aim of this study is to investigate the effects of long-term exposure to low concentrations of norgestrel (NGT) on the reproductive and thyroid endocrine systems of adult zebrafish. Adult zebrafish were exposed to 7 and 39 ng/L NGT for a duration of 90 days. The results revealed that exposure to 39 ng/L NGT led to a significant up-regulation of 3β-hydroxysteroid dehydrogenase (hsd3b) and 20β-hydroxysteroid dehydrogenase (hsd20b) genes in the ovary of female zebrafish. Additionally, there was a significant up-regulation of 11β-hydroxysteroid dehydrogenase 2 (hsd11b2) gene in the testis of male zebrafish. Furthermore, egg production decreased significantly, accompanied by notable alterations in the proportion of ovarian development stages, as well as reductions of sex hormone levels (E2, 11-KT, and T) in both females and males. However, long-term exposure to low concentrations of NGT did not lead to changes in thyroid hormone levels and thyroid histopathology in adult zebrafish. The overall results imply that environmental concentrations of NGT have a strong endocrine disrupting effect on the reproductive system of zebrafish, while the thyroid system is not sensitive to NGT exposure. The present study underscores the reproductive endocrine impacts of NGT and emphasizes the necessity for prolonged exposure at environmental concentrations.

Participation of the insulin-like growth factor system in the early maturity in juvenile male European sea bass

It is known that the insulin-like growth factor (Igf) system is involved in gonadal development and, in turn, reproduction in vertebrates. In this study, the circulating levels of Igf-1 and follicle-stimulating hormone (Fsh) were assessed as physiological signals related to gonadal maturation stage in juvenile male European sea bass at 1 year of age. The seasonal profiles of Igf-1 and Fsh were analyzed in non-precocious (NP) and precocious (PR) fish during the early onset of puberty. Subsequently, gonadal expression patterns of the three igf genes and their two receptors, igf-1r and igf-2r, were studied during their first year of life. The analysis was continued to evaluate the mRNA expression profiles of three genes (sox17, scf, nf2) mediating spermatogenesis progression. Collectively, these results demonstrated that PR males have higher circulating levels of Igf-1 as compared to NP fish before and during the putative gonadal development period (PGD). Plasma Fsh levels were significantly higher in PR males as compared to NP fish before the start of the PGD period, although this was followed by a decrease in Fsh levels and a subsequent recovery, coinciding with the reproductive season (February). Results showed that the total variance associated with the appearance of precocity may be explained by the contribution of factors such as body size and plasma levels of Igf-1, Fsh and sex steroids in male sea bass. Expression of igfs was high during stage I, and this was significantly correlated with the expression of genes related to cell cycle progression, including sox17, scf and nf2. Finally, the decreased expression of all these gonadal factors in precocious animals suggests their potential involvement in regulating the proliferative growth of spermatogonia and supporting cells during the early stages of spermatogenesis, thus evoking the onset of puberty in male sea bass.

Is Seven Days Enough? Comparing A 7-Day Exposure to the Classical 21-Day OECD TG 229 Fish Short-Term Reproduction Assay in Fathead Minnow.

The OECD (Organisation for Economic Co-operation and Development) test guidelines (TG) 229-fish short-term reproduction assay (FSTRA) is one of the gold standard methods used to identify endocrine disrupting chemicals (EDCs). While informative, the FSTRA's 5-6week duration makes it difficult to use routinely. Prior studies have shown that EDCs' impact on fecundity, vitellogenin (VTG) and steroid levels can be detected after less than 1week of exposure suggesting the FSTRA could be shortened. This study compares both 7- and 21-day FSTRAs using fathead minnows (Pimephales promelas) for three known EDCs: 17α-ethinylestradiol (EE2; 40ng/L), 17β-trenbolone (TRB; 50µg/L), and propiconazole (PRP; 500µg/L). All three compounds led to arrested fertility after 24h of exposure, except for the 7-day EE2 treatment which still decreased reproduction. Moreover, independently of time of exposure, EE2 induced VTG production in males, and decreased estrogen levels in females and testosterone levels in males. In contrast, TRB-induced VTG production in males, while the levels were not different from controls in females even though testosterone levels increased, and masculinization was observed. Finally, PRP led to a decrease in VTG levels which was only significant during the 21-day exposure, and surprisingly, no effect on steroid levels were observed despite its known effects on steroidogenesis. For two of the three EDCs tested, both times of exposure led to similar outcomes supporting the shortening of the FSTRA to seven days. This proposed 7-day FSTRA could be used to screen EDCs in routine monitoring of environmental samples.

Protective effect of active and nano-naringenin on methotrexate -induced oxidative stress in male rats’ reproductive system

In this study, which aimed to determine the preventive effect of Naringenin extracted from citrus aurantifolial on the damage caused by the methotrexate, in which 30 male rats were used, divided into five groups, which were control group dosed with Normal Saline (G1), second group dosed with methotrexate (G2) , third group dosed with Naringenin (15 to 15.5 mg) (G3), four group dosed with methotrexate and active Naringenin (G4) , fifth group dosed with methotrexate and Naringenin nanoparticles (G5) for two months, it was found that significantly increase the level of sex hormones and sperm parameters in G3 , G5 compared to G2 . It was also found that active Naringenin , Naringenin nanoparticles works to repair damage to the tissues of the testicles, epididymis and accessory glands caused by methotrexate the experimental group administered with G3,G4 and G5 had a typical testicular tissue shape characterized by tubules. Spermatozoa exhibit an elliptical morphology and are organized in a systematic and orderly fashion. the basement membrane envelops each tubule and contains sperm-generating cells, including dispersed Sertoli cells with triangle nuclei sperm progenitors In conclusion, the results of this article revealed It was found that Naringenin alone and Naringenin nanoparticles with the drug gave the best results on the methotrexate -induced male rats reproductive system

Effects of 17α-methyltestosterone and letrozole on growth and gonadal development in largemouth bass (Micropterus salmodies).

In order to optimize the parameters for reversing masculinization and establish the techniques for sex induction of pseudo-males and creation of all-female fry in largemouth bass (Micropterus salmodies, LMB), 15-day-old LMB (1.00 ± 0.10cm in length, 0.10 ± 0.01g in weight) were fed a diet supplemented with either 17α-methyltestosterone (MT) or letrozole (LE) and their combination. The experimental groups were M20 (20mg/kg MT), L20 (20mg/kg LE) and M10L10 (10mg/kg MT and 10mg/kg LE). The control group, named C, was not feed MT or LE. After 60 days, exogenous hormone in the diets was stopped and the effects of MT and LE on growth, male ratio, and gonadal development in LMB were evaluated. At 12-month-old, blood and gonadal tissue samples were collected to measure sex steroid hormones levels, analyze expression levels of dmrt1 and cyp19a1a genes, as well as examine the gonads morphology. The results showed no significant differences in growth between the experimental groups and the control group after a 60-day feeding period with the formulated diet (p > 0.05). The sex reversal ratio of M20, L20, M10L10 were 95.00%, 80.00%, 76.47%, respectively. The gonadal tissue sections showed that the gonadal structure of masculinized fish morphologic resembled that of control male fish. At 12-month-old, the sex reversal ratio in M20, L20, M10L10 and C groups were 100%, 86.67%, 73.33% and 50.00%, respectively. The testicular of pseudo-male fish in the M20 group exhibited well-developed morphology similarities to that of the control group males. However, the testes of pseudo-male fish in the L20 and M10L10 groups were smaller size Estradiol (E2) levels in the experimental groups was significantly lower than those in the control group females (p < 0.05), while testosterone (T) levels were significantly higher than that of the control group (p < 0.05). Compared to the female fish in the control group, pseudo-male fish from all experimental groups showed significantly upregulated expression of dmrt1 (p < 0.05), and significantly downregulated expression of cyp19a1a (p < 0.05). Pseudo-males selected from group M20 exhibited a significantly higher proportion of female offspring (92.00%) compared to the control group (46.50%). In summary, 20mg/kg MT was the optimal inducing concentration.

Gender-specific alteration of steroid metabolism and its impact on viral replication in a mouse model of hepatitis B virus infection

ABSTRACT Hepatitis B virus (HBV) is a sex-specific pathogen that is more severe in males than in females. Sex disparities in HBV infection have been attributed to hormonal differences between males and females. However, whether HBV infection affects the metabolic signatures of steroid hormones and how these influences viral replication remains unclear. In this study, we investigated whether HBV infection alters steroid metabolism and its effects on HBV replication. Serum samples from male and female mice obtained after the hydrodynamic injection of replication-competent HBV plasmids were subjected to quantitative steroid profiling. Serum steroid levels in mice were analyzed using an in vitro metabolism assay with the mouse liver S9 fraction. The alteration of steroids by HBV infection was observed only in male mice, particularly with significant changes in androgens, whereas no significant hormonal changes were observed in female mice. Among the altered steroids, dehydroepiandrosterone (DHEA) levels increased the most in male mice after HBV infection. An in vitro metabolism assay revealed that androgen levels were significantly reduced in HBV-infected male mice. Furthermore, the genes involved in DHEA biosynthesis were significantly upregulated in HBV-infected male mice. Interestingly, reduced dihydrotestosterone in male mice significantly inhibits viral replication by suppressing HBV promoter activity, suggesting a viral strategy to overcome the antiviral effects of steroid hormones in males. Our data demonstrated that HBV infection can cause sex-specific changes in steroid metabolism.

Features of true gynecomastia in adult males

In recent years, the incidence of gynecomastia in adult men has increased significantly. It is of interest to study the specific features of the disease in these patients. To identify the main characteristics of acute gynecomastia in adult men. A continuous one-stage study including 160 adult males with acute onset gynecomastia, who were he was treated in Endocrinology Research Centre, Moscow. Total bilirubin, hepatic transaminases, creatinine, urea, luteinizing hormone, prolactin, sex hormone binding globulin, estradiol, total testosterone, alpha-fetoprotein, chorionic gonadotropin and mammary gland condition were evaluated in all patients. Baseline significance threshold level of p&lt;0.05. The incidence of gynecomastia increased from 5,4% in 2020 to 14,4% in 2024. Tumor forms of gynecomastia were rare, with 1,2% (95% CI 0,0; 3,0) of cases. In 30% (95% CI 22,9; 37,1) of men, gynecomastia was due to the intake of anabolic steroids for athletic stimulation. In 11,2% (95% CI 6,4; 16,1) of patients, gynecomastia was hepatogenic. In 7,5% (95% CI 3,4; 11,6), it was due to elevated sex hormone binding globulin. 47,5% (95% CI 39,8; 55,2) were endocrine non-tumorigenic form of gynecomastia due to excess body weight with formation of changes in sex hormone levels. The patients who took anabolic steroids were characterized by young age, as well as decreased luteinizing hormone levels and increased testosterone levels. The group of patients with elevated sex hormone binding globulin had no clinically significant features. Men from the group of hepatogenic gynecomastia were characterized by hyperestrogenism. Patients in the group with altered sex hormone levels were characterized by high body mass index and either increased estradiol or decreased testosterone or a combination of both. The number of adult male patients with acute gynecomastia is progressively increasing. In the examined sample of patients, the main causes of gynecomastia were patients taking anabolic steroids, liver dysfunction and weight gain with the formation of changes in sex hormone levels. Patients taking anabolic steroids were characterized by a drug--induced increase in testosterone and estradiol levels, which was accompanied by suppression of pituitary gonadotropic function. Estradiol elevation was also characteristic of patients with hepatogenic form of gynecomastia and men with excess body weight with formation of changes in sex hormone levels.

Anti-Müllerian hormone deficiency leads to two distinct ovarian phenotypes with different alterations of sex hormones in gynogenetic carp

Anti-Müllerian hormone (Amh) plays conserved roles in gonadal development and function in vertebrates. Previous studies have demonstrated that amh deficiency results in severe gonadal hypertrophy in teleost. Here, we report a novel phenotype of gonadal atrophy caused by amh knockout in fish. Firstly, it was found that the amh gene had three alleles and was expressed in the cytoplasm of follicle cells in gynogenetic amphiploid gibel carp (Carassius gibelio). Subsequently, we constructed a mutant line of amh and identified two distinct ovarian abnormalities in gibel carp. Most mutants exhibited hypertrophic ovaries with increased proliferation and decreased differentiation of early germ cells, which is consistent with previously reported findings. Intriguingly, a small number of mutants displayed atrophic ovaries with decreased proliferation and premature differentiation of germ cells, which represents a novel phenotype in fish species. Transcriptome analysis revealed that these two distinct ovaries of amh mutants showed different alterations in the sex hormone biosynthesis pathway, when compared with wild-type ovaries. Furthermore, diverse gonadal sex hormone levels were also detected in these two abnormal ovaries, which were consistent with the transcriptional expressions of corresponding genes in the sex hormone synthesis pathway. These findings identify a novel atrophic ovarian phenotype of amh mutants and confirm the amh function in controlling the balance between proliferation and differentiation of germ cells in fish.

Association of LEAF-Q and EDE-QS scores with cholesterol levels in Finnish female athletes

ObjectiveLow energy availability (LEA) is common in athletes. Disturbances in sex hormone levels due to insufficient energy availability have been suggested to influence cholesterol metabolism and impact the overall risk...

Acrylamide exposure, sex hormones, and pubertal status in Japanese adolescents

ABSTRACT Acrylamide may affect sex hormone levels and the timing of sexual maturation. The present study cross-sectionally examined interrelationship between the urinary metabolite of acrylamide exposure, serum sex hormone levels, and pubertal status in 408 Japanese adolescents aged 13–14 years. Their caregivers completed a questionnaire concerning the health status of their children, including pubertal maturation, and the lifestyles of children and parents. Pubertal status was queried by the Pubertal Development Scale. A major metabolite of acrylamide, N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA) in first-void urine samples. In male students, urinary AAMA was significantly inversely associated with testosterone, puberty stage, and facial hair growth after controlling for covariates. Serum testosterone and DHEAS were significantly positively associated with puberty stage. In female students, urinary AAMA was not associated with puberty stage, the indices, or any measured hormones. The data suggest that exposure to acrylamide may impact the pubertal development of boys through the effects on testosterone level.

Sex-specific causal effects of serum sex hormones on COVID-19 susceptibility and severity: Evidence from the UK Biobank and COVID-19 Host Genetics Initiative

BackgroundSeveral hormone therapies, such as androgen receptor signaling inhibition, are being investigated for their potential effectiveness against coronavirus disease 2019 (COVID-19). However, the causal relationships between serum sex hormones and the predisposition to, as well as the severity of, COVID-19, with a particular emphasis on potential gender-specific impacts, remain elusive. MethodsIn this study, using the latest data from the UK Biobank (up to 424,907 individuals) and COVID-19 Host Genetics Initiative (up to 1,878,143 individuals), we conducted a two-sample Mendelian randomization (MR) to systematically assess the sex-specific causal effects of serum sex hormone levels, total testosterone (TT), bioavailable testosterone (BT) in particular, on COVID-19 outcomes. The inverse-variance weighted method was used in the main MR analysis. Furthermore, we additionally performed a series of sensitivity analyses to assess the robustness of MR effect estimates against potential biases caused by invalid genetic variants. ResultsOur MR analysis revealed novel causal associations between bioavailable testosterone and serum estradiol levels, and SARS-CoV-2 infection in women, but not men, except for a suggestive inverse causal association between estradiol levels and COVID-19 severity in men. ConclusionThese novel findings improve our understanding of the sex-specific causal nature of androgen and estrogen in relation to COVID-19 outcomes, and suggest that bioavailable testosterone and estradiol levels may serve as potential therapeutic targets for preventing SARS-CoV-2 infection and improving patient outcomes.

Testosterone treatment impacts the intestinal microbiome of transgender individuals.

Medical modulation of sex hormone levels is a cornerstone of treatment for many conditions that impact well-being, including cancer, fertility/infertility, gender dysphoria, and chronic metabolic diseases such as diabetes and obesity. The microbial residents of the intestine, known as the microbiota, interact with sex hormones in the intestine, and there is correlative evidence that this interaction is bidirectional. Based on these published findings, we hypothesized that transgender individuals receiving exogenous testosterone as part of their gender-affirming medical treatment might undergo changes in their intestinal microbiome. To test this, we collected 26 stool samples from nine individuals before and up to 8 months after initiation of treatment with exogenous testosterone and subjected these samples to metagenomic analysis. While no species were significantly associated with the duration of testosterone therapy, pathways that generate glutamate increased in abundance, while those that consume glutamate decreased. Glutamate is a precursor of arginine, and testosterone is known to increase levels of arginine and its metabolites in the plasma. We hypothesize that testosterone increases the uptake of glutamate by enterocytes, thus decreasing access of the microbiota to this amino acid. While this pilot study establishes the impact of testosterone therapy on the intestinal microbiome, a more comprehensive study is necessary to establish the impact of testosterone-driven metagenomic shifts on the stool metatranscriptome, the stool metabolome, and the plasma metabolome.IMPORTANCEThe human intestine is inhabited by a large community of microbes known as the microbiome. Members of the microbiome consume the diet along with their human host. Thus, the metabolomes of the host and microbe are intricately linked. Testosterone alters the plasma metabolome. In particular, plasma levels of arginine and its metabolites and testosterone are positively correlated. To investigate the impact of exogenous testosterone on the microbiome, we analyzed the stool metagenomes of transgender individuals before and after the initiation of testosterone treatment. In this pilot project, we found a modest impact on the microbiome community structure but an increase in the abundance of metabolic pathways that generate glutamate and spare glutamate consumption. We propose that the host uses glutamate to generate arginine, decreasing the amount available for the microbiome.

In situ active sampling of steroid hormones in water using a novel TIMFIE device: Validation and applicability

Monitoring trace levels of endocrine-disrupting steroid hormones in water is essential in environmental assessment, necessitating development of appropriate sampling techniques. Grab/passive sampling methods are commonly used, but use of time-integrated microflow in-situ extraction (TIMFIE) for sampling steroid hormones remains unexplored. This study aimed to evaluate the feasibility of TIMFIE samplers equipped with a hydrophilic-lipophilic balanced sorbent for monitoring seven different steroid hormones in different water matrices. Method validation demonstrated good reproducibility and accuracy of the TIMFIE samplers for extracting almost all target hormones in surface water and effluent wastewater, but not influent wastewater. Method quantification limit (0.4 ng L−1) of TIMFIE samplers for estrone (E1) in surface water and effluent wastewater met EU Water Framework Directive requirements. Comparison of TIMFIE samples and the parallel flow-based composite samples confirmed the consistency of E1, estradiol (E2), 17α-ethinylestradiol, and dienogest measurements in effluent wastewater. With TIMFIE samplers deployed in surface water, the time-weighted average concentrations of E1 (0.5–1.5 ng L−1) and E2 (0.3–0.4 ng L−1) were found below the predicted no-effect concentrations, indicating low risk to aquatic organisms. Given the challenges in assessing trace levels of steroid hormones in waters, TIMFIE as active, time-integrated samplers is a promising, green sampling tool for efficient, resource-conscious in situ extraction of steroid hormones, allowing a sustainable monitoring of these chemicals in the environment, including conditions under frozen-surfaced water bodies.

Unveiling the mechanisms of reproductive toxicity induced by full life-cycle exposure to environmentally relevant concentrations of tris(2-chloroethyl) phosphate in male zebrafish

Tris (2-chloroethyl) phosphate (TCEP), a commonly used organophosphate flame retardant, has garnered considerable concern owing to its pervasive presence in the environment and its toxic effects on living organisms. The perpetuation of populations and species hinges on successful reproduction, yet research into the mechanisms underlying reproductive toxicity remains scant, particularly in aquatic species. In this work, zebrafish embryos were exposed to TCEP (0, 0.8, 4, 20, and 100 µg/L) for 120 days until sexual maturation, and multiple reproductive endpoints were investigated in male zebrafish. Our results showed that the body weight, body length, and gonadal-somatic index (GSI) were remarkably decreased in all TCEP treatment groups (except GSI in the 0.8 µg/L TCEP-treated group). Long-term exposure to TCEP led to reduced reproductive capacity of male zebrafish, as evidenced by decreased fertilization. Histological observation gave an indication of delayed testicular development and inhibited spermatogenesis under TCEP stress. The content of testosterone (T) was significantly elevated in all TCEP treatment group, whereas 17 β-estradiol (E2) levels remained stable. Transcriptome analysis revealed a lot of downregulated genes involved in steroid hormone biosynthesis, energy metabolism, and sperm motility, which might account for the imbalance of steroid hormone levels, retarded spermatogenesis and declined fertilization success. Overall, these findings offered a thorough understanding of the mechanisms underlying the male reproductive toxicity caused by TCEP, highlight the risk of TCEP on reproductive health of fish.

Transcription repression of estrogen receptor alpha by ghrelin/Gq/11/YAP signaling in granulosa cells promotes polycystic ovary syndrome.

Polycystic ovarian syndrome (PCOS) is a prevalent endocrinological disorder affected by ghrelin. This study aimed to investigate the molecular mechanisms underlying the effects of ghrelin on PCOS manifestations in mice and to assess the therapeutic potential of ghrelin. Female C57BL/6 mice were subcutaneously injected with 6 mg/100 g dehydroepiandrosterone (DHEA) for 20 days to induce PCOS. Alterations in reproductive cycles, ovarian morphology, serum sex hormone levels, and related signaling markers were examined. Furthermore, ghrelin-induced effects on granulosa cells and the role of ghrelin/Gq/11/ Yes-associated protein (YAP) signaling were studied by silencing Gαq/11 or YAP using si-RNAs. Finally, we evaluated the therapeutic potential of anti-ghrelin antibodies in DHEA-induced PCOS mice. DHEA administration led to significant PCOS-associated changes including weight gain, disrupted estrous cycles, ovarian morphological alterations, and hormonal imbalances in mice, with elevated Gαq/11 and acylated ghrelin expression, which was also noted in PCOS patients. However, treatment with anti-ghrelin antibodies effectively managed DHEA-induced damage in PCOS mice. In vitro, ghrelin exposure resulted in granulosa cell injury and modulated estrogen receptors alpha (ERα) and YAP protein levels, whereas silencing YAP and Gαq/11 reversed ghrelin-induced detrimental effects and up-regulated ERα expression. This study revealed that DHEA-induced PCOS traits in mice could be improved by anti-ghrelin antibodies, with the ghrelin/Gq/11/YAP signaling pathway identified as a crucial mediator in granulosa cells, affecting ERα transcription to regulate PCOS. These findings suggest a potential therapeutic strategy for the treatment of PCOS.