17β-estradiol Levels Research Articles

Insights into the early gonad development of the protogynous ballan wrasse (Labrus bergylta)

The reproductive biology of ballan wrasse, a popular cleaner fish species now bred in captivity, is not well understood particularly the early stages of development and their accompanying endocrine changes. The protogynous nature of this species has been well documented in the wild, although it is still unclear if it follows a monandric or diandric hermaphroditism. In this study, we investigated the gonad development of hatchery produced ballan wrasse (n = 102) between 3 and 185 g body weight and 5–19 cm total length. About 90 % of all fish examined showed gonads undergoing primary oocyte growth, exhibiting chromatin-nucleolar stage, perinucleolar stage, and early cortical alveolar stage. Mean size of fish that entered primary oocyte growth (i.e., chromatin-nucleolar stage) is 26.2 ± 1.6 g and 10.9 ± 0.2 cm. The remaining 10 % were undifferentiated and constituted the smallest fish examined. The gonadosomatic index and circulating levels of 17β-Estradiol and Testosterone increased as fish progressed through the ovarian development. Expression levels of selected gonadal genes including cyp19a1a, figla, bmp15, dmrt1, amh, fshr, and lhr were also quantified. To the best of our knowledge, this paper is the first to investigate the early reproductive development of ballan wrasse, providing important insights into histological and endocrine changes. Results from this study provide basis for further research on the reproductive physiology of ballan wrasse as well as for the development of broodstock management techniques in this economically important cleaner fish.

Effects of light spectra on the ovarian maturation and maternal immunity in the little yellow croaker (Larimichthys polyactis)

Before spawning, fish ovaries undergo multiple events to prepare for embryogenesis. Although light plays a vital role in ovarian development and neuroendocrine activities, it is unclear how it affects ovarian maturation in the little yellow croaker (Larimichthys polyactis). This study aimed to investigate the influence of different light spectra [i.e., red, blue, dark, green, white, and ambient] on the gonadosomatic index (GSI) and hepatosomatic index (HSI); histology of the ovary; vitellogenin (VTG) levels in hepatic cells; plasma 17β-estradiol and growth hormone (GH) levels; total length; body weight; and innate/adaptive immune factors in captive-bred L. polyactis. The plasma 17β-estradiol levels gradually decreased from Jan 8 to Apr 9, and were higher in the red, green, and blue groups than in the white, dark, and control groups. By the end of the experiment, the VTG levels were significantly higher in the red group than in the control, white, and dark groups, while those in the blue group were the lowest among the treatments. The HSI fluctuated among the groups and was higher in the control, white, and green groups on Apr 9. The proportion of oocytes at stage IV was highest in the red group, which also exhibited the best synchronization of oocyte maturation. Maternal immunoglobulin M levels were significantly higher in the red and green groups than in the control, blue, dark, and white groups at the end of the experiment, while there was no significant difference in the complement component 3 (C3) levels. Collectively, these findings demonstrate that different light spectra affect 17β-estradiol secretion, VTG production, follicle synchronization and maternal immunity during ovarian maturation in L. polyactis.

Assessment of reproductive toxicity in adult zebrafish (Danio rerio) following sublethal exposure to penthiopyrad

Penthiopyrad (PO), a succinate dehydrogenase inhibitor (SDHI) fungicide, poses a potential risk to fish. Here, we investigated the adverse effects of PO on endocrine regulation and reproductive capacity in zebrafish during a 21-d sublethal exposure to PO concentrations ranging from 0.02 to 2.00 mg/L. Following exposure to PO (0.20 and 2.00 mg/L), female-specific effects including follicle necrosis, structural disturbance of the yolk follicle, fusion of cortical follicles appeared in ovarian tissue of adult females, which led to a significant reduction in fertility. Correspondingly, 0.20 and 2.00 mg/L PO led to a marked reduction in the GSI values of females, and 2.00 mg/L PO caused a 31% decline in the proportion of perinucleolar oocytes (PCO) in oocytes. In addition, testosterone (T) level was obviously suppressed and 17β-estradiol (E2) level was increased in females after exposure to 2.00 mg/L PO. Male zebrafish treated with 0.20 and 2.00 mg/L of PO exhibited significant interstitial enlargement, edema in the testes, and reduced diameter of seminiferous tubules, along with a thinner basement membrane. The effects of PO on males were associated with significant increase in E2 level, suggesting that PO has an estrogenic effect on male fish. Greater E2 levels in serum were further supported by increased transcription levels of genes linked to the hypothalamic-pituitary-gonad-liver (HPGL) axis. Notably, transcription levels of cyp19a, er2b, era, and cyp19b was remarkably increased, exhibiting a clear link with variations in E2 levels. Overall, the present study demonstrates that PO induces reproductive impairment in zebrafish by promoting steroidogenesis.

Activation or inhibition of NF-κB from the juvenile stage results in skewed sex ratios in common carp (Cyprinus carpio L.)

Due to sexual dimorphism in growth traits, all-female populations and populations with a high proportion of females hold significant economic value in common carp (Cyprinus carpio L.). However, the underlying mechanisms governing gonadal differentiation remain inadequately understood. NF-κB, as a crucial regulator of anti-apoptotic processes, plays a significant role in mammalian gonad formation and zebrafish oocyte maintenance. To investigate the potential roles of the NF-κB pathway in the gonad differentiation of common carp, juveniles with undifferentiated gonads were treated with an activator (DOC) or inhibitor (NAI) of NF-κB. Our findings revealed that juveniles exposed to DOC exhibited a significantly increased female-to-male ratio (from 0.97:1 to 4.30:1) and substantial increases in weight and body length. Conversely, inhibiting NF-κB with NAI resulted in a decreased female-to-male ratio (from 1.06:1 to 0.33:1). Furthermore, NAI also induced the occurrence of ovotestis. Additional in vivo and ex vivo experiments demonstrated that DOC activation of the NF-κB pathways led to inhibition of apoptosis, significant increases in serum 17β-estradiol (E2) levels and the E2/T ratio, and upregulation of the female-biased genes foxl2 and cyp19a1a. Simultaneously, it significantly suppressed serum 11-ketotestosterone (11-KT) levels and the expression of male-biased genes amh, dmrt1, and gsdf and induced VTG levels in the hepatopancreas of male carp. However, NAI exhibited contrasting effects. Both DOC and NAI disrupted the balance of the hypothalamus-pituitary-gonad (HPG) reproductive axis at multiple potential loci, including changes in the expression levels of steroid hormone synthesis-related genes in gonads. Transcriptomic analysis revealed comprehensive molecular changes in undifferentiated gonads during DOC-induced feminization and NAI-induced masculinization. The transcriptome results were consistent with the observed alterations in hormone content and the expression of genes involved in sex hormone synthesis, inflammation, and apoptosis following exposure to DOC or NAI. These findings suggest the involvement of NF-κB in the sex differentiation of common carp by regulating apoptosis and disrupting the HPG reproductive axis. Our study also explores a DOC-induced method of producing high ratios of females and discovers the underlying mechanism of NF-κB's contribution to sex differentiation in common carp.

Comparison of 17β-estradiol, bisphenol-A and caffeine concentration levels before and after the water treatment plant.

This article compares the concentration levels of 17β-estradiol (E2), bisphenol-A (BPA) and caffeine (CAF) in the Sinos River, Brazil, which is a source of drinking water and the presence of contaminants after the conventional treatment in a municipal water treatment plant (WTP). A total of nine sampling campaigns were carried out, with sample collection in the Sinos River, upstream and downstream of the WTP, in addition to a drinking water sample (DW). The samples were extracted with solid phase extraction (SPE) and the concentration by liquid chromatography coupled to mass spectrometry (LC-MS). The maximum concentration in the Sinos River was 6,127.99 ng·L-1 for E2, 3,294.63 ng·L-1 for BPA and 1,221.95 ng·L-1 for CAF. In drinking water, the concentration range of E2, BPA and CAF was from less than the Detection Limit (DL) up to 437.50 ng·L-1, <DL up to 2,573.34 ng·L-1 and <DL up to 832.30 ng·L-1, respectively. In conclusion, the concentrations of these pollutants present in the Sinos River are high, which may represent a negative environmental impact on this water source. Drinking water indicates the need for a new treatment process that could promote the removal of these compounds.

Integrated transcriptomic and metabolomic analyses identify key factors in the vitellogenesis of juvenile Sichuan bream (Sinibrama taeniatus)

Vitellogenesis is the most important stage of ovarian maturation in fish, involving the synthesis and transport of essential yolk substances and their complex mechanisms and coordination process. The liver is the main tissue involved in the vitellogenesis of oviparous animals, but studies of vitellogenesis in fish rarely include the liver and ovary as a whole. The aim of this study was to explore the molecular mechanism and associated regulatory factors behind vitellogenesis in Sichuan bream (Sinibrama taeniatus). The different stages of oogenesis were first identified by successive histological observations. Then, ovary and liver tissues that developed to 115 days (stage II, previtellogenesis stage), 165 days (stage III, vitellogenesis stage) and 185 days (stage IV, late-vitellogenesis stage) were collected for transcriptomic and metabolomic analyses, and serum testosterone (T), 17β-estradiol (E2), vitellogenin (Vtg), triiodothyronine (T3), and thyroxine (T4) levels were measured at the corresponding stages. We found that energy redistribution during vitellogenesis is mainly regulated through glycolysis, fatty acid biosynthesis and the citrate cycle pathway. In the liver, energy metabolism was promoted by activating glucolipid metabolic pathways to provide sufficient ATP, but at the same time, the ovary tends to retain nutrients rather than decompose them to produce energy. In addition, we have identified several key factors involved in the metabolism of neutral lipids, polar lipids, amino acids and vitamins, which are involved in the assembly and transport of important yolk nutrients. The initiation of vitellogenesis was found to be associated with a surge in serum E2 levels, but the sustained increase in Vtg levels in the late stage may be due more to upregulation of the estrogen receptor. These results provide valuable information about the regulation of ovarian development in cultured fish.

Protective Effects of Ginger Extract on Oxidative Stress and Steroidogenesis-related Genes in The Ovary of Streptozotocin-induced Diabetic Rats

Background and Aims: Ginger has anti-oxidant and anti-diabetic properties, but its beneficial effects have not been fully understood on ovarian disorders in diabetic conditions. In the current project, the impact of ginger extract was investigated on oxidative stress and steroidogenesis-related genes in streptozotocin (STZ)-induced female rats. &#x0D; Materials and Methods: The STZ-induced rats were utilized as a diabetic model and received 200 or 400 mg/kg/day ginger extract for eight weeks. The biochemical factors were measured by standard procedures in this study. Serum levels of insulin and sex hormones were assessed by the enzyme-linked immunosorbent assay (ELISA) technique, and the mRNA expression of target genes was assayed by real-time polymerase chain reaction.&#x0D; Results: An increase in the levels of glucose, testosterone, and malondialdehyde (MDA) as well as a decrease in the levels of insulin, glutathione peroxidase (GPx), 3β-hydroxysteroid dehydrogenase (3βHSD), steroidogenic acute regulatory protein (StAR), 17β-estradiol, and progesterone was observed in the diabetic rats. Ginger (200 mg/kg) exhibited a significant amelioration in the levels of glucose, testosterone, and MDA. Treatment with 200 mg/kg ginger enhanced the levels of GPx, StAR, and 17β-estradiol. Administration with 400 mg/kg ginger extract also ameliorated the level of glucose, testosterone, MDA, and elevated the level of insulin, GPx, 3βHSD, StAR, 17β-estradiol, and progesterone in the diabetic rats.&#x0D; Conclusion: The current study suggests ginger extract protects against ovarian damage in STZ-diabetic rats.

Fenugreek Seed Ethanolic Extract Improves Alveolar Bone Parameters by Attenuating Inflammation in Ovariectomized Rats.

Alveolar bone residual ridge resorption remains a major challenge for dental implant placement in patients with edentulism. Fenugreek seed extracts have been reported to have potential roles in bone metabolism. This study aimed to evaluate the effects of fenugreek seed ethanolic extract (FSEE) on bone cells, inflammation, hormones, and angiogenesis parameters of alveolar bone tissue following teeth extraction in an ovariectomized (OVX) model. A total of 30 adults female Wistar rats were assigned into two major groups. Each group consisted of control, OVX, OVX+FSEE 100 mg/kg BW, OVX+FSEE 200 mg/kg BW, and OVX+FSEE 400 mg/kg BW. The FSEE treatment was applied through the intragastric route for 7 days in the first group and for 30 days in the second group of animals. The first molar tooth of the right maxilla was extracted before the FSEE treatment. The level of 17β-estradiol was measured by the ELISA method. The dissected maxilla alveolar bone processus was sectioned for histological evaluation by hematoxylin-eosin staining and an immunohistochemistry assay. This study found that FSEE reduced the blood estrogen level and increased estrogen receptor-α (ER-α) expression. FSEE administration modified the number of bone cells, angiogenesis, vascular endothelial growth factor (VEGF), sclerostin, and the osteoprotegerin/receptor activator of nuclear factor kappa-β ligand (OPG/RANKL) ratio. Alterations were seen in the inflammatory markers interleukin-6 (IL-6), transforming growth factor-β1 (TGF-β1), and the macrophage-1/macrophage-2 (M1/M2) ratio. In this study, inflammation was found to be attenuated by reductions in IL-6 and sclerostin, and an increase in TGF-β1. The maturation of bone osteocytes increased along with the increase in ER-α expression and ratio of OPG/RANKL.

B-178 Clinical Routine Ultrasensitive LC-MS/MS Method Development for Analysis of 17β-Estradiol in Human Serum

Abstract Background The increasing clinical demand for the measurement of circulating 17β-Estradiol at very low concentrations consolidates the need of highly sensitive and specific analytical methodologies. These assays are suitable in situations such as antiestrogen therapy monitoring (use of aromatase inhibitor in breast cancer treatment); diagnosis of suspect inherited sex-steroid metabolic disorders; diagnosis of precocious and delayed puberty in female; hormone replacement therapy in postmenopausal women; and estrogen deficiency in men. Time-consuming methods and lack of sensitivity are common in the quantification of 17β-Estradiol in serum by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The strategy of chemical derivatization is common for analysis of estrogens because it enhances specificity and sensitivity, but this approach becomes laborious in the sample preparation process. For the purpose of solving these analytical challenges, the aim of this work was developing a reliable, sensitive and low-cost LC-MS/MS method without derivatization for clinical routine analysis. Methods Isotope-labeled internal standard 17β-Estradiol-D5 were added to calibrators, quality controls (QC) and serum samples before a liquid-liquid extraction with the organic solvent Diethyl Ether. After reconstitution, the extracts were injected into a Biphenyl column 50 × 2.1 mm, 2,6 µm, chromatographic separated by solvent gradient (Ammonium Fluoride in Water – Acetonitrile) and detected in positive electrospray ionization mode. The analytical method was validated using reference material grade standards and spiked QCs in charcoal stripped pool patient serum at 4 levels by the assessment of linearity, limit of quantification (LoQ), precision inter and intra-assay, accuracy, carryover, method comparison, cross-reactivity and stability (freeze-thawing cycles, bench top, postoperative and stock solution). Results The method has been validated with the analytical measurement range of 2–500 pg/mL. It was successfully optimized to achieve low levels of 17β-Estradiol as proposed with limit of quantitation of 2 pg/mL. Within-run and between-run precision (coefficient of variation) study yielded 1.3%–7.2% and accuracy within 95.7%–112.1%. No carryover, matrix effect and significant cross-reactivity was observed. Estradiol was found to be stable in serum samples under 3 freeze/thawing cycles, 4 h at ambient temperature and 72 h after extraction procedure in auto-injector. The stability of stock solutions was tested in −20 °C freezer and remained stable for 1 month. Method comparison between two reference laboratories (LC-MS/MS method) was performed and the results showed acceptable data for regression statistics (slope (a) = 0.9184; intercept (b) = −0.1576), t-test statistics (bias = 8.5%) and difference plot. Conclusion An ultrasensitive and derivatization-free LC-MS/MS method was developed and it may be beneficial for patients with endocrine disorders associated with estradiol levels.

Single and mixture toxicity evaluation of avobenzone and homosalate to male zebrafish and H295R cells

Avobenzone and homosalate are widely used in sunscreens to provide ultraviolet (UV) protection, either as single compounds or in combination. Some UV filters exhibit estrogenic or anti-androgenic activities, however, studies regarding their interactions and toxicity in mixtures are limited. In this study, the effect of the toxicity of a binary mixture comprising avobenzone (0.72 μg L−1) and homosalate (1.02 and 103 μg L−1) on steroid hormone biosynthesis were investigated using male zebrafish and human adrenocortical carcinoma (H295R) cells. In fish exposed to homosalate, a significant decrease in the gonadosomatic index, testosterone level, and transcription of several genes (e.g, hsd3b2, cyp17a1, and hsd17b1) and a significant increase in the hepatosomatic index, liver steatosis, 17β-estradiol level, and transcription of vtg gene were observed. These results suggest that estrogenic and anti-androgenic effects of homosalate were mediated by the steroidogenic pathway. The presence of 0.72 μg L−1 of avobenzone augmented the anti-androgenic responses in male fish. The testosterone level in the H295R cells were significantly decreased after they were exposed to homosalate alone or in combination with avobenzone, which is consistent with observations in male zebrafish. Further studies need to be conducted to understand the endocrine disrupting properties of long-term exposure to substances typically used in sunscreens.

Effects of Di-(2-Ethylhexyl) Phthalate (DEHP) on Gamete Quality Parameters of Male Koi Carp (Cyprinus carpio).

In this study, we evaluated gamete quality parameters of mature male koi carp (Cyprinus carpio) exposed to three different concentrations (1, 10, and 100 µg/L) of di-(2-ethylhexyl) phthalate (DEHP). After 60 days of exposure, there was a significant decrease in the gonadosomatic index (GSI) of males exposed to 10 and 100 µg/L of DEHP. Histological analysis of the testes revealed impaired histoarchitecture, including inflammatory cells, intratubular vacuoles, and swollen seminiferous tubules in treatment groups. Gamete quality parameters like sperm production, motility, spermatocrit, and sperm density values were significantly decreased at the 10 and 100 µg/L concentrations. Biochemical compositions, including glucose, cholesterol, and total protein levels, were significantly changed in the treatment groups. Similarly, the ionic compositions of seminal fluid (Na, K, Ca, and Mg) also varied in the treatment groups. Furthermore, the 11-ketotestosterone levels were decreased, and the 17-β estradiol levels were increased in the DEHP-treated groups. The mRNA expression levels of reproduction-related genes, including Fshr, Lhr, Ar, Erα, and Erβ, were significantly changed in the DEHP-treated males in a dose-dependent manner. In conclusion, the findings of this study confirmed that environmentally relevant exposure to DEHP may contribute to a decline in the gamete quality of male fishes.

Comparable bio-evaluation of curcumin and chitosan-encapsulated curcumin nanoparticles against the reprotoxic potential of fenpropathrin pyrethroid in rats: Genomic and morphometric prospectives.

This study delves into the intricate exploration of potential toxic effects resulting from subchronic exposure to fenpropathrin (FNP) on the reproductive system of male SD rats. Adding to the novelty, our study undertakes a pioneering comparison of the effects of curcumin (CUR) and curcumin-encapsulated chitosan nanoparticles (CS.CUR.NPs) on these toxic effects. The study involved a cohort of sixty male SD rats (six groups): vehicle control, CUR, Cs.CUR.NPs, FNP, and two combination groups (FNP with CUR or Cs.CUR.NPs). The synthesized Cs.CUR.NPs nanoparticles underwent meticulous characterization using Fourier Infrared spectroscopy (FT-IR) and transmission electron microscopy (TEM). The findings revealed that FNP caused oxidative stress, sperm abnormalities, reduced motility and sperm count FNP decreased serum LH, FSH, 17-β estradiol, and testosterone levels. FNP downregulated the mRNA expression of the spermatogenesis and steroidogenesis-related genes, While, downregulated hypothalamic KISS-1 and KISS-1r expression. Histopathological alterations were assessed and scored. Surprisingly, the treatment with CUR and Cs.CUR.NPs exhibited remarkable restorative effects on semen quality, sex hormone levels, antioxidant capacity, and mRNA expression of the targeted genes. Notably, Cs.CUR.NPs displayed superior properties when compared to CUR. Nevertheless, further research is imperative to evaluate their efficacy across various bodily tissues.

Dietary rumen-protected L-arginine or N-carbamylglutamate enhances placental amino acid transport and suppresses angiogenesis and steroid anabolism in underfed pregnant ewes

This study aimed to investigate the effects of dietary supplementation of underfed Hu ewes from d 35 to 110 of gestation with either rumen-protected L-arginine (RP-Arg) or N-carbamylglutamate (NCG) on placental amino acid (AA) transport, angiogenic gene expression, and steroid anabolism. On d 35 of gestation, 32 Hu ewes carrying twin fetuses were randomly divided into four treatment groups, each consisting of eight ewes, and were fed the following diets: A diet providing 100% of NRC's nutrient requirements for pregnant ewes (CON); A diet providing 50% of NRC's nutrient requirements for pregnant ewes (RES); RES diet plus 5 g/d NCG (RES + NCG); or RES diet plus 20 g/d RP-Arg (RES + ARG). On the d 110 of pregnancy, blood samples were taken from the mother, and samples were collected from type A cotyledons (COT; the fetal portions of the placenta). The levels of 17β-estradiol and progesterone in the maternal serum and both the capillary area density (CAD) and capillary surface density (CSD) in type A COT were decreased in response to Arg or NCG supplementation when compared to the RES group. The concentrations of arginine, leucine, putrescine and spermidine in type A COT were higher (P < 0.05) in the RES + ARG or RES + NCG group than in the RES group. The mRNA expression levels of inducible nitric oxide synthase (iNOS) and solute carrier family 15, member 1 (SLC15A1) were increased (P < 0.05) while those of progesterone receptor (PGR) and fibroblast growth factor 2 (FGF2) were decreased in type A COT by supplementation with either NCG or RP-Arg compared to the RES group. The results suggest that providing underfed pregnant ewes from d 35 to 110 of gestation with a diet supplemented with NCG or RP-Arg improves placental AA transport, and reduces the expression of angiogenic growth factor genes and steroid anabolism, leading to better fetal development.

Decamethylcyclopentasiloxane affects estradiol production in female rats but not H295R cells.

Sex hormones, such as androgens and estrogens, are predominantly produced in the gonads (ovaries and testes) and adrenal cortex. Endocrine-disrupting chemicals (EDCs) are substances that mimic, block, or interfere with hormones in the endocrine systems of humans and organisms. EDCs mainly act via nuclear receptors and steroidogenesis-related enzymes. In the OECD conceptual framework for testing and assessment of EDCs, several well-known assays are used to identify the potential disruption of nuclear receptors both in vivo and in vitro, whereas the H295R steroidogenesis assay is the only assay that detects the disruption of steroidogenesis. Forskolin and prochloraz are often used as positive controls in the H295R steroidogenesis assay. Decamethylcyclopentasiloxane (D5) was suspected one of EDCs, but the effects of D5 on steroidogenesis remain unclear. To establish a short-term in vivo screening method that detects the disruption of steroidogenesis, rats in the present study were fed a diet containing forskolin, prochloraz, or D5 for 14 days. Forskolin increased plasma levels of 17β-estradiol (E2) and testosterone as well as the mRNA level of Cyp19 in both the adrenal glands and ovaries. Prochloraz induced the loss of cyclicity in the sexual cycle and decreased plasma levels of E2 and testosterone. D5 increased E2 levels and shortened the estrous cycle in a dose-dependent manner; however, potential endocrine disruption was not detected in the H295R steroidogenesis assay. These results demonstrate the importance of comprehensively assessing the endocrine-disrupting effects of chemicals on steroidogenesis in vivo.

The Efficacy of Nigella sativa L. and Curcumin Nanomicelle Alone or Together on Lipid Profile, Glycemic Control Indices, and Serum 17-Β Estradiol in Postmenopausal Women.

Menopause is a condition for metabolic disorders. This study aimed to evaluate the effect of Nigella sativa (NS), curcumin nanomicelle (CN), lipid profile, glycemic status and 17-β estradiol (ES) levels in postmenopausal women. Triple-blind randomized clinical trial was conducted on 120 postmenopausal women. Participants were randomly assigned to four groups: 1) NS capsule 1000 mg and CN placebo, 2) 80 mg CN capsule and NS placebo, 3) both NS and CN capsules and 4) NS and CN placebo. Participants received a single dose daily for 6 months. The serum lipid profile, glycemic control biomarkers, and ES were measured pre-and post-intervention using biochemical methods. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, fasting blood sugar (FBS), fasting insulin (FI), insulin resistance (IR), and ES showed significant improvement in NS group. CN significantly reduced TC, FI, and IR, and significantly increased ES. The combination of NS-CN significantly decreased TC, LDL, FI, and IR, and increased HDL and ES. The comparison of the studied with the placebo groups showed that these changes were significant in glycemic indices and NS significantly increased estrogen. NS, CN and NS-CN improved lipid profiles, blood sugar, and hormone levels. However, this improvement was significant in glycemic indices and estrogen levels compared to the placebo group. No superiority of combined NS-CN over NS or CN was found in this trial.

Benzophenone-2 exerts reproductive toxicity in male rats

Benzophenone derivatives such as benzophenone-2 (BP-2) belong to the group of endocrine disrupting compounds (EDCs). Increased exposure to EDCs is considered to be an important factor behind the decline of human fertility. The main aim of the present study was to determine the effect of BP-2 on testicular function specified by sperm analysis, the level of sex hormones and their receptors. Since BP-2 has been shown to activate the immune system, another aim of the research was to verify the hypothesis that the immune system may be contributing to the testis toxicity of this compound and for this purpose changes in macrophage and lymphocyte populations in the testes were determined. BP-2 at a dose of 100 mg/kg was administered dermally, twice daily at a dose of 100 mg/kg for 4-weeks. It was shown that BP-2 reduced the number and motility of sperm and increased the number of sperm showing morphological changes. By determining the concentration of sex hormones, a significant decrease in testosterone levels and an increase in the blood levels of 17β-estradiol were demonstrated. Similar to the results obtained from the blood samples, testosterone levels in the testes were lowered, which could affect sperm parameters. The effect of BP-2 on lowering testosterone levels and the number of sperm cells may be due to immunoactivation in the testes, because it has been detected that this compound significantly decreased the number of the immunosuppressive resident testicular macrophages (TMs) (CD68-CD163+), but increased pro-inflammatory TMs with monocyte-like properties (CD68+CD163-).

Effect of long-term hypoxia on the reproductive systems of female and male yellow catfish (Pelteobagrus fulvidraco).

This study investigated the effects of different levels of hypoxia on the reproductive system of yellow catfish. Yellow catfish (Pelteobagrus fulvidraco) were exposed to three dissolved oxygen concentration levels: normoxia (6.5 ± 0.2 mg/L), moderate hypoxia (MH, 3.8 ± 0.3 mg/L) and severe hypoxia (SH, 1.9 ± 0.2 mg/L) for 30 days. The gonadosomatic index of males, not females, significantly decreased in the SH group. In the SH group, for the females, the ratio of vitellogenic follicles significantly decreased, whereas the number of atretic follicles significantly increased. In male fish, a significantly reduced number of spermatozoa was observed in both the MH and SH groups. Elevated apoptosis levels in the testes and ovaries were observed only in the SH group. Serum 17β-estradiol and vitellogenin levels in females and testosterone levels in males significantly decreased in the SH group. The concentration of 11-ketotestosterone in males significantly decreased in both the MH and SH groups. In female fish, dysregulated expression of the hypothalamic-pituitary-gonadal (HPG) axis, steroidogenesis genes, and hepatic genes related to vitellogenesis were observed only in the SH group. However, in male fish, moderate hypoxia altered the expression of HPG genes, including gnrh1, lhcgr, and amh. Moreover, the MH group significantly altered the expression of steroidogenesis genes like star, 17β-hsd, and cyp17a1. The results of this study suggest that severe hypoxia can cause reproductive defects in female and male yellow catfish. Moreover, the reproductive system of male yellow catfish is more sensitive to moderate hypoxia than that of female catfish. Our findings contribute to our understanding of the response of the teleost reproductive system to long-term hypoxia.

Correlation analysis of polyamine metabolism and reproductive hormone levels in goose ovarian follicles

To investigate the relationship between polyamine metabolism and reproductive hormones in ovarian follicles of Sichuan white geese, follicle polyamine content and reproductive hormone levels and gene expressions related to polyamine metabolism, steroidogenesis and steroid hormone receptors were detected by HPLC, ELISA and RT-qPCR. The results showed that the overall trend of spermidine and spermine levels increased first and then decreased as increasing follicle size, with the highest level in F3 and F5 follicles (P < 0.05). Putrescine and 17β-estradiol (E2) levels in hierarchical follicles were significantly lower than those in prehierarchical follicles (P < 0.05). Progesterone (P4) first increased and then decreased, with the highest level in the F5 follicle (P < 0.05). The expression levels of estrogen receptor 1 (ER1) showed an overall increase as increasing follicle size (except in F3 follicles), while estrogen receptor 2 (ER2) in hierarchical follicles was significantly lower than that in the prehierarchical follicles (P < 0.05). In addition, the overall expression level of progesterone receptor (PR) decreased, with no significant differences among F1, F2 and F3 follicles (P > 0.05). Yolk putrescine contents were positively correlated with yolk E2 concentrations and PR expression levels (P < 0.05), A significant positive correlation of spermidine levels with yolk P4 concentrations and PR expressions was also observed, as well as the spermine levels with yolk P4 concentrations (P < 0.05). In summary, polyamines were involved in the regulation of follicular development in geese, and this regulation played a role in affecting steroidogenesis and the expression of genes related to hormone receptors.

Women’s Brain Health: Midlife Ovarian Removal Affects Associative Memory

Women with early bilateral salpingo-oophorectomy (BSO; removal of ovaries and fallopian tubes) have greater Alzheimer’s disease (AD) risk than women in spontaneous/natural menopause (SM), but early biomarkers of this risk are not well-characterized. Considering associative memory deficits may presage preclinical AD, we wondered if one of the earliest changes might be in associative memory and whether younger women with BSO had changes similar to those observed in SM. Women with BSO (with and without 17β-estradiol replacement therapy (ERT)), their age-matched premenopausal controls (AMC), and older women in SM completed a functional magnetic resonance imaging face-name associative memory task shown to predict early AD. Brain activation during encoding was compared between groups: AMC (n=25), BSO no ERT (BSO; n=15), BSO+ERT (n=16), and SM without hormone therapy (n=16). Region-of-interest analyses revealed AMC did not contribute to functional group differences. BSO+ERT had higher hippocampal activation than BSO and SM. This hippocampal activation correlated positively with urinary metabolite levels of 17β-estradiol. Multivariate partial least squares analyses showed BSO+ERT had a different network-level activation pattern than BSO and SM. Thus, despite being approximately 10 years younger, women with BSO without ERT had similar brain function to those with SM, suggesting early 17β-estradiol loss may lead to an altered functional brain phenotype which could influence late-life AD risk, making face-name encoding a potential biomarker for midlife women with increased AD risk. Despite similarities in activation, BSO and SM groups showed opposite within-hippocampus connectivity, suggesting menopause type is an important consideration when assessing brain function.

Estradiol- and Progesterone-Associated Changes in microRNA-Induced Silencing and Reduced Antiseizure Efficacy of an Antagomir in Female Mice.

About one-third of individuals living with epilepsy have treatment-resistant seizures. Alternative therapeutic strategies are thus urgently needed. One potential novel treatment target is miRNA-induced silencing, which is differentially regulated in epilepsy. Inhibitors (antagomirs) of specific microRNAs (miRNAs) have shown therapeutic promise in preclinical epilepsy studies; however, these studies were mainly conducted in male rodent models, and research into miRNA regulation in females and by female hormones in epilepsy is scarce. This is problematic because female sex and the menstrual cycle can affect the disease course of epilepsy and may, therefore, also alter the efficacy of potential miRNA-targeted treatments. Here, we used the proconvulsant miRNA miR-324-5p and its target, the potassium channel Kv4.2, as an example to test how miRNA-induced silencing and the efficacy of antagomirs in epilepsy are altered in female mice. We showed that Kv4.2 protein is reduced after seizures in female mice similar to male mice; however, in contrast to male mice, miRNA-induced silencing of Kv4.2 is unchanged, and miR-324-5p activity, as measured by the association with the RNA-induced silencing complex, is reduced in females after seizure. Moreover, an miR-324-5p antagomir does not consistently reduce seizure frequency or increase Kv4.2 in female mice. As a possible underlying mechanism, we found that miR-324-5p activity and the silencing of Kv4.2 in the brain were differentially correlated with plasma levels of 17β-estradiol and progesterone. Our results suggest that hormonal fluctuations in sexually mature female mice influence miRNA-induced silencing and could alter the efficacy of potential future miRNA-based treatments for epilepsy in females.