Estradiol Research Articles

INVESTIGATION OF SEX HORMONE CONCENTRATIONS IN MALE WHITE RATS AND THE QUANTITATIVE AND ANATOMICAL CHANGES IN THEIR OFFSPRING FOLLOWING CHRONIC HALOPERIDOL ADMINISTRATION

Objectives: To investigate the effects of chronic, dose-dependent haloperidol administration on the concentration of sex hormones (total testosterone (Ttotal), free testosterone (Tfree), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PL), progesterone (PG), estriol (ER), estradiol (ED)), as well as fertilization rates, and the quantitative and anatomical parameters of offspring in male white rats. Materials and Methods. The study was conducted on 54 white rats (both sexes, weighing 170-190 g) housed at the Scientific Research Center of Azerbaijan Medical University. The animals were divided into three groups, each consisting of 12 male rats and 6 female rats. The effects of chronic haloperidol administration on sex hormone concentrations and the quantitative and anatomical parameters of the offspring were examined. Results. Chronic administration of haloperidol at doses of 0.5 mg/kg and 3 mg/kg to male white rats resulted in a statistically significant, dose-dependent decrease in the levels of sex hormones: Ttotal, Tfree, FSH, LH, PG, ER, and ED (except PL). In females mated with haloperidol-treated males, significant alterations in pregnancy outcomes were observed. Compared to the control group, haloperidol administration reduced the number of offspring, caused abnormalities in their appearance, led to stillbirths, and delayed the opening of the auditory canal and the formation of the primary hairline. Additionally, a “reverse geotaxis” reaction was observed in the offspring. Conclusion. Compared to the control group, 2 offspring were born in the group receiving chronic haloperidol at a dose of 0.5 mg/kg, while 3 offspring with congenital anomalies were born in the group receiving chronic haloperidol at a dose of 3 mg/kg. Significant changes in the course of pregnancy and visible deviations from the norm during childbirth were observed in females mated with male rats treated with haloperidol. Visual inspection of the offspring 24-48 hours after delivery revealed abnormalities, including asymmetry of the skull and facial skeleton, abnormal limb, tail, eye socket, nostril, and oral slit development, in both experimental groups.

Evaluating the estrogenic activity and toxicity of Tectona grandis leaf extract on the reproductive and endocrine system of female wistar rats

Female reproductive complications continue to be a major health challenge worldwide. Medicinal plants richer in secondary metabolites such as phytoestrogens have been used over decades for the treatment of reproductive health problems like infertility, with limited knowledge on their toxicities. The present study was designed to evaluate the estrogenic potential and safety of Tectona grandis leaves extract on female wistar rats. Following acclimatization and pre-evaluation of the estrous cycle, female wistar rats, 6 weeks old were placed in groups of 3 animals each and T. grandis extracts administered daily in graded doses of 500, 1000, 2000mg/Kg body weight against controls for 28 days (Sub-acute toxicity). A dose dependent increase in 17-Beta estradiol was observed in the serum and ovary homogenates versus an increase in cholesterol when compared to the control groups. Results from the three animals per group showed an increase in the weights of the animals and a non-significant increase in alanine aminotransferase (ALT), white blood cells, haemoglobin and haematocrit at the dose of 2000 mg/kg. Also, there was no significant difference in the organ weights and histopathological examinations of necropsied animals showed no abnormalities in the various organs. T. grandis leave extract contains phytochemicals such as lignans that can be converted by microflora to phytoestrogens, which can compete with endogenous estrogen for the estrogen receptor potentiating similar activities like estrogens. This indicates that T. grandis could be explored as hormonal replacement therapies in infertility, menopausal and/or breast cancer related problems. Keywords: 17-β-estradiol, Tectona grandis, lignans, phytoestrogens, toxicity, hormonal replacement therapy

Estradiol deficiency as a consequence of aging contributes to the depletion of the satellite cell pool in female mice.

The effects of aging on the satellite cell pool have primarily been studied in male mice, where the role of cell-intrinsic versus environmental changes on satellite cell function remains contentious. Estradiol is necessary for maintenance of satellite cell pool size in adult female mice-here we investigate the hypothesis that in females, estradiol is a major environmental driver of age-associated effects on satellite cells. In 24-26 month-old ovarian senescent mice, we find the satellite cell pool size is severely diminished in certain muscles (TA and EDL) but only marginally affected in others (soleus and gastrocnemius). Supplementation with 17-beta estradiol significantly increases satellite cell pool size in the TA and EDL. To assess cell-intrinsic versus environmental regulation, we perform two transplantation experiments, Adult or Aged satellite cells transplanted into Adult recipients, and Adult satellite cells transplanted into Adult or Aged mice. These results demonstrate that the aged environment dominates over cell-autonomous age in terms of the specification of satellite cell pool size. Transcriptional profiling on satellite cells from Adult, Aged and ovariectomized mice revealed commonalities across the two estradiol-deficient conditions, Aged and ovariectomized, in GO terms from differentially expressed genes. Our findings support the hypothesis that the lack of estradiol contributes to reductions in satellite cell number in Aged female muscle, yet cells that remain are functional in terms of proliferative potential and self-renewal capacity. These findings have implications for sex hormone treatment of menopausal women and highlight the vital role of estradiol in the maintenance of the satellite cell pool.

The Potential Influence of the Presence of Mycotoxins in Human Follicular Fluid on Reproductive Outcomes.

The effect of mycotoxin exposure on follicular fluid composition and reproductive outcomes in women undergoing in vitro fertilisation (IVF) was investigated in this study. Twenty-five patients were included, and follicular fluid and serum samples were analysed for various mycotoxins. Principal observations:1. Mycotoxin presence: All examined mycotoxins were detected in follicular fluid. Follicular fluid (ff) levels: Deoxynivalenol (DON), alfa-Zearalenol (α-ZOL), Zearalenone (ZEN), and total aflatoxin (AFs) were significantly higher in follicular fluid than in serum. 2. Follicular fluid and reproductive outcomes: A positive correlation was observed between the ratio of oocytes to total follicles and the follicular Fumonisin B1 (FB1) levels. Multiple linear regression analysis revealed a significant relationship between DON and T-2/HT-2 toxins (T2/HT2) levels in the follicular fluid. 3. Hormone levels: Follicular 17-beta estradiol (E2) and progesterone (P4) levels were higher than the serum levels. Follicular P4 correlated with serum P4 and Anti-Müllerian hormone (AMH) levels. In contrast, follicular E2 did not correlate with plasma E2 levels. 4. Mycotoxin-hormone interactions: A positive correlation was observed between follicular P4 and T2/HT2 toxin levels, whereas a negative correlation was found between ffE2 and ffT2/HT2, and a positive correlation was found between ZEN and E2. Conclusion: This study elucidated the presence of various mycotoxins in the follicular fluid and their potential influence on reproductive outcomes. Further research is warranted to clarify the specific mechanisms underlying these effects and develop strategies for detecting mycotoxin exposure in women undergoing IVF.

Morphology-controlled composite of conductive Cu CATs nanorods and bimetallic PdPt nanospheres for electrochemical sensitive detection of 17β-estradiol

Different synthetic methods can effectively adjust the morphology of the composite to affect the electrochemical properties. In this paper, Cu-catecholates (Cu CATs) was synthesized by solvothermal method, and bimetallic PdPt nanospheres (PdPt) was prepared by controllable one-step reduction. Subsequently, Cu CATs and PdPt were compounded to form the composite Cu CATs/PdPt. The excellent conductivity of the Cu CATs/PdPt composite was derived from the strong charge delocalistion between the Cu active centers in the MOFs and the ligand triphenyl-2,3,6,7,10,11-hexanol (HHTP) with a two-dimensional (2D) π-conjugated structure and the large specific surface area of PdPt nanospheres. The catalytic performance was mainly attributed to the Cu active centers in Cu CATs, the synergistic interaction of Pd and Pt in PdPt nanospheres and the numerous active sites on account of the large specific surface of the Cu CATs/PdPt composite. Therefore, it can be used as a platform for electrochemical signal amplification. The Cu CATs/PdPt non-enzymatic electrochemical sensor can detect the concentration of estradiol (ED) from 5 nM to 30 μM (R2 = 0.9954), and the detection limit was 3.8 nM (S/N = 3). This sensor can be applied to the ED detection of real samples (human urine) and has promising application prospects in the fields of biosensing and environmental monitoring.

Abstract PR001: An immunomodulatory crosstalk between cancer cells and the hepatic microenvironment underlies mutant estrogen receptor-driven breast cancer-to-liver metastasis

Abstract While major advancements have been made in treatment of primary tumors in estrogen receptor-positive (ER+) breast cancer, reducing mortality from metastatic breast cancer (mBC) in treated patients who develop endocrine resistance to first line therapies remains an unmet clinical need. Wild-type ER activity or availability of its cognate ligand 17-beta estradiol (E2) are major factors in primary tumor progression, which are lost/reduced due to endocrine treatments, such as use of selective estrogen degraders (SERDs) and aromatase inhibitors (AIs), respectively. Over time, this leads to selection of rare cancer cells bearing point mutations in ESR1, the gene encoding ER-alpha, which become the dominant population at metastatic sites, and such mutations are now recognized as a frequent driver of endocrine resistance and metastasis, especially in patients with advanced ER+ breast cancer who have been heavily pre-treated with AIs. Analyses of clinical samples have shown a statistically significant association enrichment of ESR1 mutations in liver metastases, compared to the primary tumor. Other distant tissues commonly colonized by breast cancer cells, such as bones, lungs, or brain, although prevalent, do not display this strong association. While this might be due to ease of biopsy sampling in the liver compared to other sites, an alternate and intriguing hypothesis is that the liver offers a fertile soil for metastatic colonization by mutant ER-expressing cells, compared to other distant sites, such as lungs. Using a combination of pre-clinical models, we assessed if mutant ER could drive metastatic colonization at distant sites, such as the liver. We have uncovered a novel link between cancer cell-intrinsic immunomodulatory signaling pathways that are specifically upregulated in mutant ER-expressing breast cancer cells, which represents at least one major molecular mechanism underlying the observed liver tropism of mutant ER-associated, endocrine resistant ER+ breast cancer. We show that disseminated, mutant ER-expressing BC cells engage in crosstalk with the liver stromal and immune populations post-extravasation to further fuel metastatic outgrowth. Citation Format: Sunny Das, Joana Liu Donaher, Lisa Verhoeven, Ranjan Mishra, Ferenc Reinhardt, Sumeet Gupta, Zheqi Li, Kornelia Polyak, Robert A. Weinberg. An immunomodulatory crosstalk between cancer cells and the hepatic microenvironment underlies mutant estrogen receptor-driven breast cancer-to-liver metastasis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr PR001.

The Effect of Ginger (Zingiber Officinale Roscoe) and Turmeric (Curcuma Longa) Supplementation on 17-β Estradiol Level, Quality of Life and Body Composition in Postmenopausal Women: Secondary Outcomes of a Randomized, Placebo controlled Trial

The Effect of Ginger (Zingiber Officinale Roscoe) and Turmeric (Curcuma Longa) Supplementation on 17-β Estradiol Level, Quality of Life and Body Composition in Postmenopausal Women: Secondary Outcomes of a Randomized, Placebo controlled Trial

7606 Partial Xp Duplication and Xq Deletion in a Patient with Premature Ovarian Failure: A Rare Case Report

Abstract Disclosure: A. Pataco: None. C.S. Moniz: None. C. Chaves: None. R. Medeiros: None. M. Ponte: None. B.D. Pereira: None. J. Anselmo: None. I. Sousa: None. Premature ovarian failure (POF) is a heterogeneous condition characterized by the cessation of ovarian function leading to amenorrhea before age 40. While the etiology of POF is diverse, the majority of cases are idiopathic, with a likely genetic basis. Xq abnormalities are commonly linked to POF, whereas Xp abnormalities are rare and infrequently reported.We describe a case of a 30-year-old woman with a personal history of depression, presenting to the Endocrinology department with an 8-month history of amenorrhea. Notably, her menstrual cycles had been irregular since menarche. Previously, a gynecological assessment led to the initiation of bromocriptine 5 mg/day for suspected microprolactinoma, indicated by symptoms of galactorrhea, elevated prolactin levels (112 ng/mL; Normal: 5.18-26.53), and a pituitary MRI showing a 3.5mm microadenoma. It is important to note her concurrent use of risperidone, sertraline, and lorazepam at that time.In the first evaluation at the Endocrinology department, the patient reported amenorrhea and denied galactorrhea. The physical examination was unremarkable with no evidence of hirsutism. The blood tests indicated hypergonadotropic hypogonadism, low levels of prolactin and Anti-Müllerian hormone: FSH 17 mIU/mL (Normal: 3.03-8.08), LH 8.30 mIU/mL (Normal: 1.80-11.78), 17-Beta Estradiol 11 pg/mL (Normal: 21-251), Total testosterone 20.1 ng/dL (Normal: 7.21-79.31), TSH 1.84 uIU/mL (Normal: 0.35-4.94), T4L 1.06 ng/dL (Normal: 0.70-1.48), PRL 1.8 ng/mL (Normal: 5.18-26.53), ACTH 21 pg/mL (Normal: 7.2-63.3), Cortisol 11.5 ug/dL (Normal: 3.7-19.4), IGF-1 130.2 ng/mL (Normal: 177-382), Anti-Müllerian hormone <0.1 ng/mL (Normal: 0.3-11.2).A diagnosis of premature ovarian failure was established. Bromocriptine was discontinued, and the hyperprolactinemia was attributed to the iatrogenic effects of her medications. A pelvic ultrasound showed no abnormalities. Cytogenetic analysis revealed an abnormal karyotype: 46 chromosomes with one X chromosome showing an anomalous configuration—partial deletion of the long arm and partial duplication of the short arm [duplication X(p22.33p11.23) with over 100 genes and deletion X(q24q28) including the FMR1 gene].The patient started hormone replacement therapy with estradiol valerate and medroxyprogesterone acetate, achieving regular menstruation thereafter. Literature review reveals that POF cases involving both partial Xp duplication and partial Xq deletion are exceedingly rare (only 6 reported cases). Genetic counseling is recommended for these patients, particularly for those considering parenthood. It is also advisable to assess the chromosomal alteration in parents to determine if the change is inherited and to evaluate the risk to other family members. Presentation: 6/2/2024

7606 Partial Xp Duplication and Xq Deletion in a Patient with Premature Ovarian Failure: A Rare Case Report

Abstract Disclosure: A. Pataco: None. C.S. Moniz: None. C. Chaves: None. R. Medeiros: None. M. Ponte: None. B.D. Pereira: None. J. Anselmo: None. I. Sousa: None. Premature ovarian failure (POF) is a heterogeneous condition characterized by the cessation of ovarian function leading to amenorrhea before age 40. While the etiology of POF is diverse, the majority of cases are idiopathic, with a likely genetic basis. Xq abnormalities are commonly linked to POF, whereas Xp abnormalities are rare and infrequently reported.We describe a case of a 30-year-old woman with a personal history of depression, presenting to the Endocrinology department with an 8-month history of amenorrhea. Notably, her menstrual cycles had been irregular since menarche. Previously, a gynecological assessment led to the initiation of bromocriptine 5 mg/day for suspected microprolactinoma, indicated by symptoms of galactorrhea, elevated prolactin levels (112 ng/mL; Normal: 5.18-26.53), and a pituitary MRI showing a 3.5mm microadenoma. It is important to note her concurrent use of risperidone, sertraline, and lorazepam at that time.In the first evaluation at the Endocrinology department, the patient reported amenorrhea and denied galactorrhea. The physical examination was unremarkable with no evidence of hirsutism. The blood tests indicated hypergonadotropic hypogonadism, low levels of prolactin and Anti-Müllerian hormone: FSH 17 mIU/mL (Normal: 3.03-8.08), LH 8.30 mIU/mL (Normal: 1.80-11.78), 17-Beta Estradiol 11 pg/mL (Normal: 21-251), Total testosterone 20.1 ng/dL (Normal: 7.21-79.31), TSH 1.84 uIU/mL (Normal: 0.35-4.94), T4L 1.06 ng/dL (Normal: 0.70-1.48), PRL 1.8 ng/mL (Normal: 5.18-26.53), ACTH 21 pg/mL (Normal: 7.2-63.3), Cortisol 11.5 ug/dL (Normal: 3.7-19.4), IGF-1 130.2 ng/mL (Normal: 177-382), Anti-Müllerian hormone <0.1 ng/mL (Normal: 0.3-11.2).A diagnosis of premature ovarian failure was established. Bromocriptine was discontinued, and the hyperprolactinemia was attributed to the iatrogenic effects of her medications. A pelvic ultrasound showed no abnormalities. Cytogenetic analysis revealed an abnormal karyotype: 46 chromosomes with one X chromosome showing an anomalous configuration—partial deletion of the long arm and partial duplication of the short arm [duplication X(p22.33p11.23) with over 100 genes and deletion X(q24q28) including the FMR1 gene].The patient started hormone replacement therapy with estradiol valerate and medroxyprogesterone acetate, achieving regular menstruation thereafter. Literature review reveals that POF cases involving both partial Xp duplication and partial Xq deletion are exceedingly rare (only 6 reported cases). Genetic counseling is recommended for these patients, particularly for those considering parenthood. It is also advisable to assess the chromosomal alteration in parents to determine if the change is inherited and to evaluate the risk to other family members. Presentation: 6/2/2024

Exploring the protective effect of silver Croton tiglium nano-extract against azoxymethane induced toxicity in female reproductive organs in rats

Reproductive toxicity from food and environmental contaminants has greatly affected human life. Plants are a fundamental source of bioactive components for relieving the harmful effects of pollutants. Hydrazine metabolites pose health threats when they enter the food chain. Croton tiglium (C. tiglium) exhibits anti-inflammatory and anti-tumor properties. Silver nanoparticles enhance the chemical stability of C. tiglium. Reproductive toxicity of Azoxymethane (AOM) and anticancer effects of silver C. tiglium were evaluated. Thirty-six adult female rats were divided into six groups (n = 6) and treated with AOM with or without silver C. tiglium nano-extract as pre- and post-treatment. Sexual hormones and proteins were assessed under silver C. tiglium nano-extract and AOM. Histopathologically, AOM caused metaplastic myometrial endometriotic cysts and endometrial metaplasia. Silver C. tiglium in pre- and post-treated rats mitigated the carcinogenic effects of AOM. Immunohistochemically, AOM carcinogenicity was evident through moderate detection of the CK-7 tumor marker in the ovaries and uterus of the AOM-, simultaneous-, and post-treated groups. C. tiglium ameliorated this, with CK-7 slightly expressed in the pre-treated group. Furthermore, C. tiglium alleviated the negative impact on FSH, LH, and 17-β estradiol hormones. In conclusion, Silver C. tiglium nano-extract successfully prevented tumors in the ovaries and uterus of AOM-treated rats.

Positive effects of a mixture of fish oil and soybean oil as a dietary lipid source on the ovarian development and health of female giant river prawn, Macrobrachium rosenbergii broodstock

Lipids are key nutrients that affect the development of the ovary in aquatic animals. This study aimed to investigate the effects of different lipid sources on the ovarian development and health of Macrobrachium rosenbergii broodstock. The M. rosenbergii broodstock, with an initial body weight of 8.07±0.74 g, were fed diets containing 5 % fish oil (FO), soya bean oil (SO), rapeseed oil (RO), coconut oil (CO), and a 1:1 mixture of fish oil and soybean oil (MO) as lipid sources for a period of 56 days. The results indicated that there were no significant differences in survival rate (SR) and hepatopancreatic index (HSI) among the different groups (P > 0.05). However, the specific growth rate (SGR) and gonadosomatic index (GSI) in the MO group were significantly higher than other groups (P < 0.05). Additionally, fatty acid levels in diets directly influenced the fatty acid composition of prawn hepatopancreas, showing a similar trend to that observed in the diet itself. Furthermore, compared to the other trial groups, haemolymph levels of 17-β estradiol (E2) and progesterone (PROG) were significantly increased in the MO group (P < 0.05). The ovarian section also exhibited better histomorphology and larger oocyte diameter in this group. Moreover, total antioxidant capacity was significantly increased in the MO group (P < 0.05). Saturated fatty acids in RO and CO groups could promote the expression of lipid synthesis-related genes fatty acid synthase (fas) and acetyl-CoA carboxylase (acc), concurrently suppressing the expression of lipid catabolism-related genes acyl-CoA oxidase-1 (acox-1) and AMP-activated protein kinase alpha (ampkα) (P < 0.05). Conversely, polyunsaturated fatty acids in the MO group significantly up-regulated the expression levels of fatty acid binding protein-3 (fabp-3) and peroxisome proliferator-activated receptor gamma (pparγ) (P < 0.05). Based on the findings of hepatopancreatic tissue structure, it was determined that the use of a single vegetable oil resulted in some damage to the hepatopancreatic tissue structure of M. rosenbergii broodstock, leading to increased oxidative stress. In conclusion, it is recommended that a 1:1 mixture of fish oil and soybean oil be used as a dietary lipid source to effectively meet the nutritional requirements during the ovarian development period of M. rosenbergii broodstock. This combination also enhances antioxidant properties, promotes the synthesis of haemolymph steroid hormones and lipid metabolism in female prawns, thereby facilitating ovarian development and overall health of M. rosenbergii broodstock.

The Effects of Quercetin on the Expression of Collagen I, Collagen III and Elastin in Vaginal: An Experimental Animal Study

Background: Vulvovaginal atrophy is part of the genitourinary syndrome of menopause caused by hypoestrogenic changes. This pathophysiological mechanism alters the concentration of collagen and elastin, which modifies the vaginal mucosa and impairs the function of the pelvic floor muscles. Quercetin is one of the flavonols found in plants, fruits, and vegetables. Quercetin helps to improve the syndrome through a variety of actions and estrogen-like effects. This study aimed to analyze the impact of quercetin on collagen I, collagen III, and elastin in a vaginal menopausal rat model. Method: This study's research design was an in vivo randomized control group post-test. The research was conducted at the animal laboratory, Faculty of Medicine, Universitas Airlangga. Rattus norvegicus, used in the study, were divided into 5 groups: normal rat, menopausal model without treatment, menopausal model given 17-β estradiol valerate 0.18 mg/kg, quercetin 12.5 mg/kg, and quercetin 50 mg/kg. The effectiveness of therapy was assessed from the immunohistochemical expression of collagen I, collagen III, and elastin in vaginal tissue. Results: The standard group in this study had the highest average expression levels of collagen I and elastin. The group of menopausal models without treatment in the study had the highest average expression of collagen III. Collagen I expression (p &lt; 0.001), collagen III expression (p &lt; 0.001), and elastin expression (p &lt; 0.001) all showed significant differences. The menopausal rat model without treatment and the standard group showed the most differences in the expression of collagen I, collagen III, and elastin. Conclusions: The expression of collagen I, collagen III, and elastin in the vagina of the menopausal model was affected by the administration of quercetin at a level of 50 mg/kg. Thus, quercetin can be an alternative herbal treatment option to improve vulvovaginal atrophy in menopausal conditions.

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 GHSR1a antagonist LEAP2 regulates islet hormone release in a sex-specific manner.

LEAP2, a liver-derived antagonist for the ghrelin receptor, GHSR1a, counteracts the effects of ghrelin on appetite and energy balance. Less is known about its impact on blood glucose-regulating hormones from pancreatic islets. Here, we investigate whether acyl-ghrelin (AG) and LEAP2 regulate islet hormone release in a cell-type- and sex-specific manner. Hormone content from secretion experiments with isolated islets from male and female mice was measured by radioimmunoassay and mRNA expression by qPCR. LEAP2 enhanced insulin secretion in islets from males (P < 0.01) but not females (P > 0.2), whilst AG-stimulated somatostatin release was significantly reversed by LEAP2 in males (P < 0.001) but not females (P > 0.2). Glucagon release was not significantly affected by AG and LEAP2. Ghsr1a, Ghrelin, Leap2, Mrap2, Mboat4, and Sstr3 islet mRNA expression did not differ between sexes, whereas the SSTR3 antagonist MK4256 enhanced glucose-induced insulin secretion in islets from males only. In control male islets maintained without 17-beta oestradiol (E2), AG exerted an insulinostatic effect (P < 0.05), with a trend towards reversal by LEAP2 (P = 0.06). Both were abolished by 72 h E2 pre-treatment (10 nmol/L, P > 0.2). AG-stimulated somatostatin release was inhibited by LEAP2 from control (P < 0.001) but not E2-treated islets (P > 0.2). LEAP2 and AG did not modulate insulin secretion from MIN6 beta cells and Mrap2 was downregulated (P < 0.05) and Ghsr1a upregulated (P < 0.0001) in islets from Sst-/- mice. Our findings show that AG and LEAP2 regulate insulin and somatostatin release in an opposing and sex-dependent manner, which in males can be modulated by E2. We suggest that regulation of SST release is a key starting point for understanding the role of GHSR1a in islet function and glucose metabolism.

HFD feeding for seven months abolishes STING disruption-driven but not female sex-based protection against hepatic steatosis and inflammation in mice

Stimulator of interferon genes (STING) is positively correlated with the degrees of liver inflammation in human metabolic dysfunction-associated steatotic liver disease (MASLD). In addition, STING disruption alleviates MASLD in mice fed a high-fat diet (HFD) for 3 months (3-m-HFD). Here we investigated the role of the duration of dietary feeding in regulating MASLD in mice and explored the involvement of STING in sex differences in MASLD. Both male and female STING-disrupted (STINGgt) and wild-type C57BL/6J mice were fed an HFD for 3 or 7 months (7-m-HFD). Additionally, female STINGgt mice upon ovariectomy (OVX) and 3-m-HFD were analyzed for MASLD. Upon 3-m-HFD, STINGgt mice exhibited decreased severity of MASLD compared to control. However, upon 7-m-HFD, STINGgt mice were comparable with wild-type mice in body weight, fat mass, and MASLD. Regarding regulating the liver RNA transcriptome, 7-m-HFD increased the expression of genes indicating proinflammatory activation of various liver cells. Interestingly, the severity of MASLD in female mice was much lighter than in male mice, regardless of STING disruption. Upon OVX, female STINGgt mice showed significantly increased severity of MASLD relative to sham control but were comparable with male STINGgt mice. Upon treatment with 17-beta estradiol (E2), hepatocytes revealed decreased fat deposition while macrophages displayed decreases in lipopolysaccharide-induced phosphorylation of Nfkb p65 and Jnk p46 independent of STING. These results suggest that 7-m-HFD, without altering female sex-based protection, abolishes STING disruption-driven protection of MASLD, likely through causing proinflammatory activation of multiple types of liver cells to offset the effect of STING disruption.

Gallic acid counteracts tartrazine-induced testicular dysfunction in rats: biochemical, histopathological and ultrastructural evidences

BackgroundTartrazine (Tz) is one of the most commonly used colorants incorporated in the food manufacturing. Its toxicity is derived from metabolic byproducts representing health hazards to consumers. Gallic acid (GA) is known for its redox stabilizing, anti-apoptotic, and cytoprotective characteristics. Therefore, the aim of this study is to explore the possible defensive effect of GA against Tz-induced testicular dysfunction. To achieve this objective, 18 male Wistar adult rats were randomly and equally categorized into three groups for 30 days. The control group received no treatment. Tz at a dose of 30 mg/kg BW was administered to the Tz group. The Tz + GA group received GA at a dose of 200 mg/kg BW in concurrent with the previously described Tz dosage. Both Tz and GA were supplemented orally once daily by a stomach tube.ResultsThe marked decline in luteinizing hormone, follicle stimulating hormone, testosterone, and estradiol 17beta confirmed deviation in pituitary–gonadal axis of Tz-exposed rats. Imbalances in plasma redox equilibrium were evident, characterized by a notable increase in malondialdehyde and nitric oxide levels, along with a decrease in reduced glutathione and total antioxidant capacity. Deteriorations in histopathological features, fibrosis in testicular tissue, abnormalities in Sertoli cell, and up-regulation in caspase-3 were observed. Conversely, GA administration successfully reversed these issues.ConclusionThe ability of GA to counteract toxicological molecular targets in Tz-exposed testes is believed to be achieved through the restoration of oxidant/antioxidant balance and the prevention of the apoptotic cascade.

Pre-conceptional paternal diet impacts on offspring testosterone homoeostasis via epigenetic modulation of cyp19a1/aromatase activity

Paternal eating habits, before and at conception, have a strong impact on offspring future metabolism. By sending specific epigenetic signals through spermatozoa, paternal nutrition influences developing embryos and increases offspring risk of developing dysmetabolism and cardiovascular diseases. Among the intergenerational consequences, paternal epigenetic messages affect embryo DNA methylation altering programmed gene expression. The identification of offspring genetic loci that are epigenetically altered by paternal stimuli is of pivotal interest for timely post-natal treatment of offspring metabolic defects. We here use a murine model to show that, cyp19a1/aromatase, a gene coding for the cytochrome converting testosterone into 17-β estradiol (both potent hormonal mediators of embryo development and metabolism), is an epigenetic transducer of paternal intergenerational inheritance. By affecting cyp19a1 methylation status and alternative splicing, paternal diet coordinates androgens’ metabolism in the progeny affecting it in a sexually dimorphic way and promoting hypoandrogenism, growth retardation and diabetes in male pups.

Effectiveness and Safety of Different Estradiol Regimens in Transgender Females: A Randomized Controlled Trial.

A goal of gender-affirming hormone therapy (GAHT) for transgender women is to use estradiol to suppress endogenous production of testosterone. However, the effects of different estradiol regimens and route of administration on testosterone suppression is unknown. This is the first open-label randomized trial comparing different GAHT regimens for optimal estradiol route and dosing. To evaluate 1 month and 6 months testosterone suppression <50 ng/dL with pulsed (once- or twice-daily sublingual 17-beta estradiol) and continuous (transdermal 17-beta estradiol) GAHT. This study was conducted at an outpatient adult transgender clinic. Thirty-nine transgender women undergoing initiation of GAHT were randomly assigned to receive either once-daily sublingual, twice-daily sublingual, or transdermal 17-beta estradiol. All participants received spironolactone as an antiandrogen. Doses were titrated at monthly intervals to achieve total testosterone suppression <50 ng/dL. Transdermal 17-beta estradiol resulted in more rapid suppression of total testosterone, lower estrone levels, with no differences in estradiol levels when compared to once-daily and twice-daily sublingual estradiol. Moreover, there was no difference in the mean estradiol dose between the once-daily and twice-daily sublingual 17-beta estradiol group. Continuous exposure with transdermal 17-beta estradiol suppressed testosterone production more effectively and with lower overall estradiol doses relative to once or twice daily sublingual estradiol. Most transgender women achieved cisgender women testosterone levels within 2 months on 1 or 2 0.1 mg/24 hours estradiol patches. Given no difference between once- or twice-daily sublingual estradiol, pulsed 17-beta estradiol likely provides no benefit for testosterone suppression.

Follow-Up Study of 17-β Estradiol, Prolactin and Progesterone with the Kinetics and Prevalence of T. gondii Infection in Pregnant Women.

Toxoplasmosis is an infection caused by the parasite Toxoplasma gondii. One-third of the world's population has come into contact with this parasite. In Mexico, the prevalence is between 15% and 50% in the general population and 34.9% in women with high-risk pregnancies. In pregnancy, the highest incidence of infection occurs in the third trimester and fetal damage is inversely proportional to gestational age. Maternal hormones play a fundamental role in the immune response. There are very few studies, with controversial results, on the levels of increased hormones and their relationship to the kinetics of T. gondii infections during pregnancy. The aim was to determine the serum levels of 17-β estradiol, prolactin, and progesterone, and their association with anti-T. gondii antibodies' kinetics in pregnancy. Fifty-two pregnant patients were studied. A questionnaire with sociodemographic and clinical aspects was used. Afterward, 10 mL of venous blood was collected by venipuncture every trimester. The concentrations of 17-β estradiol, progesterone, and prolactin were measured, using the ELISA method. In addition, anti-Toxoplasma IgG and IgM antibodies were also determined in the first, second, and third trimester. The prevalence of anti-Toxoplasma IgG antibodies was 26.92% in the first and second trimester and 32.7% in the third trimester. In seropositive women, 17-β estradiol increased in the second and third trimesters of pregnancy. Progesterone increased significantly p < 0.039 in the third trimester in these women, while prolactin increased in the second trimester with a statistical significance of p < 0.021. In addition, 17-β estradiol, progesterone, and prolactin are associated with T. gondii infection during pregnancy. New studies are necessary to clarify the specific mechanisms of immune response related to these hormones during pregnancy.

Nutritional Value of Palm Meristem from Phoenix dactylifera L. and Its Effect on Polycystic Ovary Syndrome in Female Rats Induced with Estradiol Valerate

Abstract Objective: Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder in women of reproductive age. The objective of our investigation is to study the protective effect of hydroethanolic extract of palm meristem (HEPM) on female rats with PCOS. Materials and Methods: The experimental study involved the placement of 42 adult female Wistar rats (n = 7) into six groups, with the control group receiving 0.25 ml of physiological serum by gavage daily, the sham group getting 0.25 ml of olive oil, and the HEPM 250, 500, and 500 per se group taking HEPM by gavage daily. PCOS was induced with estradiol valerate (EV), which was administered through a subcutaneous injection at 2 mg/kg volume using 0.25 ml of olive oil. After experiments, all animals were subjected to anesthesia, and serums were extracted for biochemical and hormonal evaluation. Results: EV showed marked increases in serum levels of testosterone and luteinizing hormone when compared with the control group. Significantly, the EV group decreased 17-β estradiol, progesterone, and follicle-stimulating hormone. There was a significant alteration in hormonal levels across the treatment groups. The serum malondialdehyde levels and total oxidant status were elevated in the EV group. In addition, the serum levels of total antioxidant capacity, glutathione, and glutathione peroxidase were significantly lower in the EV group than in control rats. In the treatment groups, HEPM significantly reverses the oxidant/antioxidant balance and ameliorates the adverse effect of PCOS on oxidative stress. Conclusion: The study findings indicated that the HEPM effectively safeguarded ovarian tissue from developing PCOS in the presence of EV.