Serum Estradiol Concentrations Research Articles

Association between aldehyde exposure and sex steroid hormones among adults.

Exogenous and endogenous exposure to aldehydes is seen worldwide. Aldehydes are closely associated with human diseases, especially reproductive toxicity. However, the effect of aldehyde exposure on sex steroid hormones among adults remains uninvestigated. A total of 851 participants aged over 18years were included in this cross-sectional analysis based on data from National Health and Nutrition Examination Survey (NHANES) 2013-2014. Serum aldehyde concentrations were quantified following an automated analytical method. Sex steroid hormones including total testosterone, estradiol, and sex hormone binding globulin (SHBG) were detected. Multivariate linear regression models, forest plots, generalized additive model (GAM), and smooth curve fitting analysis were used to assess the associations between quartiles of aldehydes and sex steroid hormones levels after adjusting for potential confounders. Butyraldehyde and propanaldehyde were found to be negatively associated with estradiol and SHBG in females and males, respectively. β values with 95% confidence intervals (95% CIs) were - 20.59 (- 38.30 to - 2.88) for Q2 vs. Q1 of butyraldehyde and - 8.13 (- 14.92 to - 1.33) and - 7.79 (- 14.91 to - 0.67) for Q2 vs. Q1 and Q4 vs. Q1 of propanaldehyde. No significant associations were observed between other aldehydes and sex hormones. In premenopausal women, isopentanaldehyde was inversely associated with serum total testosterone levels (Q4 vs. Q1: OR = - 7.95, 95% CI: - 15.62 to - 0.27), whereas propanaldehyde was positively associated with serum estradiol concentration (Q3 vs. Q1: β = 28.88, 95% CI: 0.83 to 56.94). Compared with Q1, Q3 of isopentanaldehyde was associated with 3.53pg/mL higher concentration of estradiol in postmenopausal women (β = 3.53, 95% CI: 0.08 to 6.97). Moreover, in males under 40years, butyraldehyde and heptanaldehyde were inversely proportional to total testosterone levels and heptanaldehyde and butyraldehyde were negatively associated with estradiol and SHBG. Decreased total testosterone, elevated estradiol, and decreased SHBG levels were found in higher quartiles of benzaldehyde, hexanaldehyde and isopentanaldehyde, and propanaldehyde, respectively, in males aged over 60years. In male participants aged 40-60years, only hexanaldehyde was observed to be correlated with higher serum estradiol levels. In conclusion, our current research presented the association between six serum aldehydes and sex hormones. Of note, stratification analyses were conducted in participants with different menopausal statuses and age among males and females. Sex- and age-specific effect of aldehyde exposure on alterations in sex hormone levels were observed. Further studies are warranted to confirm the causal relationship and explore the underlying mechanisms.

Assessing estrogen exposure from transdermal estradiol patch therapy using a dried urine collection and a GC–MS/MS assay

BackgroundTransdermal estradiol patch therapy is often dosed based on patient reported symptoms. Although dosing based on serum estradiol concentrations has been considered, serum sampling is too invasive and inconvenient to use in real-world settings. The primary aim of this study was to determine if a dried urine assay could be used to assess estrogen exposure resulting from transdermal estradiol patch therapy at increasing doses. MethodsThis was a retrospective analysis of clinical laboratory data. Urinary estrogen profiles of postmenopausal women being treated with transdermal estradiol patches at differing doses (age = 56.8 ± 7.5) were selected from the database along with the profiles of women on no therapy for comparison (age = 55.1 ± 9.5). Metabolite concentrations were obtained using a multi-spot dried urine collection and a gas chromatography-tandem mass spectrometry assay. The Jonckheere-Terpstra test was used to assess for ordered differences across dose groups to determine if dose-dependent increases in urinary estrogens occurred with increasing doses. ResultsMedian concentrations of estradiol and other estrogen metabolites increased with increasing doses of transdermal estradiol patch therapy (p < 0.001; Jonckheere-Terpstra test). For women who collected samples before and after initiating therapy, there were significant differences between before and after concentrations of estradiol and other estrogen metabolites. ConclusionThis large study conducted using real-world data demonstrated that a dried urine assay offers a viable method of assessing estrogen exposure differences that occur with the use of differing doses of transdermal estradiol patches. Further studies with prospective designs that include outcome measures are needed to confirm the findings of this study.

The impact of oocytes containing smooth endoplasmic reticulum aggregates on assisted reproductive outcomes: a cohort study

BackgroundThe impact of smooth endoplasmic reticulum aggregates (SERa) on assisted reproductive technology (ART) outcomes was still controversial. Our objective is to investigate the impact of the presence of SERa on intracytoplasmic sperm injection (ICSI) outcomes.MethodsThis was a retrospective cohort study. A total of 1,090 fresh ICSI cycles from 944 patients between January 2016 and June 2020 were included. Outcomes from clinical, embryological and neonatal aspects were compared between SERa + and SERa- cycles as well as between SERa + and SERa- oocytes.ResultsThe total gonadotropin (Gn) dose, number of oocytes retrieved, serum estradiol concentration and number of the available embryo were significantly higher in SERa + cycles than in SERa- cycles (P < 0.05). Comparable two pronuclei (2PN) fertilization rate and poly-pronucleus zygote rate were shown in SERa + and SERa- cycles (P > 0.05), but which were higher in SERa + oocytes than in SERa- oocytes (P < 0.05). No statistical difference in blastocyst formation rate was found in SERa + and SERa- cycles as well as in SERa + and SERa- oocytes (P > 0.05). Good-quality embryo rate was statistically higher in SERa- cycles than in SERa + cycles (P < 0.05), but the difference was comparable between SERa + and SERa- oocytes (P > 0.05). No statistical difference in clinical pregnancy rate, spontaneous abortion rate, live birth rate and premature delivery rate were found in SERa + and SERa- cycles as well as in SERa + and SERa- oocytes (P > 0.05). The implantation rate was comparable in SERa + and SERa- cycles (P > 0.05), but it is higher in the group of only SERa- embryo transfer when compared with the group of mixed SERa + and SERa- embryo transfer (P < 0.05). 159 newborns in SERa + cycles and 140 newborns in SERa- cycles were followed up. Comparable newborn malformation rate was observed between SERa + and SERa- cycles and oocytes (P > 0.05). Logistic regression analysis revealed number of oocytes and total dose of Gn were risk factors for SERa occurrence (aOR = 1.05 and 1.55, P < 0.001).ConclusionOocyte's SERa is correlated with a number of oocytes retrieved and higher Gn dose, but it does not affect pregnancy outcomes and increase newborn malformation rate.

Association of Vaginal Estradiol Tablet With Serum Estrogen Levels in Women Who Are Postmenopausal

Half of women who are postmenopausal have genitourinary discomfort after menopause. Recommended therapies include low-dose vaginal estrogen. Individuals with a history of breast cancer or venous thromboembolism may have concerns about the safety of this intervention. To compare serum estrogen concentrations with the use of vaginal estrogen, 10 μg, tablet vs placebo in women who are postmenopausal. This is a secondary, post hoc analysis of data from a randomized clinical trial of treatment for moderate to severe genitourinary syndrome in women who are postmenopausal. The study was conducted at Kaiser Permanente Washington Health Research Institute and the University of Minnesota from April 11, 2016, to April 23, 2017. Measurements and data analysis were performed from November 3, 2020, to September 23, 2022. Participants were randomly assigned to vaginal estradiol tablet (10 μg/d for 2 weeks and then twice weekly) plus placebo gel (3 times weekly) or dual placebo for 12 weeks. In this post hoc analysis, baseline and week 12 serum estradiol, estrone, and sex hormone-binding globulin (SHBG) concentrations were measured by a chemiluminescent assay. Week 12 values of the 3 analytes were compared by baseline participant characteristics. Linear models compared week 12 estradiol concentrations between treatment groups, adjusted for baseline characteristics. A total of 174 women, mean (SD) age 61 (4) years, were included. Those in the estrogen group (n = 88) were more likely to have higher geometric mean (SD) week 12 serum estradiol concentrations (4.3 [2.2 pg/mL]) than those in the placebo group (n = 86) (3.5 [2.1] pg/mL) (P = .01). Adjusted for pretreatment hormone concentrations, age, clinical site, and body mass index, assignment to the estrogen vs placebo treatment group was significantly associated with higher week 12 estradiol concentrations (23.8% difference; 95% CI, 6.9%-43.3%). Most (121 of 174 [69.5%]) participants had enrollment serum estradiol concentrations higher than 2.7 pg/mL. Of women starting treatment at estradiol levels lower than or equal to 2.7 pg/mL, 38.1% (8 of 21) in the estrogen group and 34.4% (11 of 32) in the placebo group had estradiol concentrations higher than 2.7 pg/mL after 12 weeks of study participation (P = .78). Treatment assignment was not associated with week 12 estrone or SHBG concentrations. In this secondary analysis of a randomized clinical trial, a significant, although small, increase in serum estradiol levels was noted after 12 weeks of vaginal estrogen administration. The clinical relevance of this small increase is uncertain. ClinicalTrials.gov Identifier: NCT02516202.

Hormonal therapies up-regulate MANF and overcome female susceptibility to immune checkpoint inhibitor myocarditis.

Immune checkpoint inhibitors (ICIs) have been increasingly used in combination for cancer treatment but are associated with myocarditis. Here, we report that tumor-bearing mice exhibited response to treatment with combinatorial anti-programmed cell death 1 and anti-cytotoxic T lymphocyte antigen-4 antibodies but also presented with cardiovascular toxicities observed clinically with ICI therapy, including myocarditis and arrhythmia. Female mice were preferentially affected with myocarditis compared to male mice, consistent with a previously described genetic model of ICI myocarditis and emerging clinical data. Mechanistically, myocardial tissue from ICI-treated mice, the genetic mouse model, and human heart tissue from affected patients with ICI myocarditis all exhibited down-regulation of MANF (mesencephalic astrocyte-derived neurotrophic factor) and HSPA5 (heat shock 70-kDa protein 5) in the heart; this down-regulation was particularly notable in female mice. ICI myocarditis was amplified by heart-specific genetic deletion of mouse Manf and was attenuated by administration of recombinant MANF protein, suggesting a causal role. Ironically, both MANF and HSPA5 were transcriptionally induced by liganded estrogen receptor β and inhibited by androgen receptor. However, ICI treatment reduced serum estradiol concentration to a greater extent in female compared to male mice. Treatment with an estrogen receptor β-specific agonist and androgen depletion therapy attenuated ICI-associated cardiac effects. Together, our data suggest that ICI treatment inhibits estradiol-dependent expression of MANF/HSPA5 in the heart, curtailing the cardiomyocyte response to immune injury. This endocrine-cardiac-immune pathway offers new insights into the mechanisms of sex differences in cardiac disease and may offer treatment strategies for ICI myocarditis.

Effect of human umbilical cord mesenchymal stem cells on ovarian function in lupus mice

AbstractBackgroundPatients with systemic lupus erythematosus (SLE) suffer from a high incidence of premature ovarian failure, which might be due to cyclophosphamide gonadal toxicity, immune abnormalities, or other reasons. This study aimed to investigate whether the transplantation of human umbilical cord mesenchymal stem cells (HUC‐MSCs) can improve ovarian reserve function in lupus mice.MethodsWe used MRL/lpr mice to observe changes in ovarian structure and secretory function in SLE. Lupus mice and controls were injected with HUC‐MSCs at Weeks 12 and 16. We detected serum concentrations of the sex hormones estradiol (E2), follicle‐stimulating hormone (FSH), and anti‐Müllerian hormone (AMH), using enzyme‐linked immunosorbent assays. Hematoxylin and eosin staining showed ovarian tissue structure and enabled the counting of follicles. Hepatocyte growth factor (HGF) and insulin‐like growth factor 1 (IGF‐1) expression in ovarian tissue was observed by immunohistochemistry.ResultsOvarian function in lupus mice was abnormal, as indicated by decreased serum E2 and AMH concentrations, and increased FSH concentrations. HUC‐MSC transplantation caused significant upregulation of serum E2 and AMH and downregulation of FSH (all p &lt; 0.05). Ovarian structure improved and the follicle number increased after HUC‐MSC transplantation. Multiple infusions of HUC‐MSCs at Weeks 12 and 16 resulted in a significantly higher number of primordial follicles than infusions of HUC‐MSCs at only Week 12 (p &lt; 0.05). Immunohistochemistry showed that IGF‐1 and HGF expression increased after HUC‐MSC transplantation, but this was not significant.ConclusionsHUC‐MSCs transplantation restores disturbed hormone secretion and folliculogenesis in lupus mice. HUC‐MSC transplantation should be repeated for the best treatment effect.

The Effects of BMI and Genetic Variation of Adipokines on Serum Concentrations of Hormones in Untreated Individuals with Breast Cancer; a Pilot Study

Background: Numerous studies have shown an association between hormones secreted by adipose tissues and cancer development. Objectives: This study aimed at investigating the effect of body mass index (BMI) and genetic variation of leptin and adiponectin on serum concentrations of leptin, adiponectin, and estradiol among untreated breast cancer. Methods: This case-control study was performed on 350 women (175 women with breast cancer and 175 healthy controls), who had not taken any medications. Serum levels of estradiol (17-beta estradiol), leptin, and adiponectin were measured, using the ELISA technique. Single-nucleotide polymorphisms of leptin gene (LepG2548A), leptin receptor (Q223, K109R, and K656N), and adiponectin gene (T45G, G276T, C11377G, and 11391A) in blood-isolated DNA were evaluated, using RFLP-PCR technique. Results: Body mass index can affect serum concentrations of hormones and is associated with breast cancer. Also, except for adiponectin C11377G polymorphism, other all genetic variations showed significant relationships with breast cancer. In both groups, BMI was significantly correlated with the mean serum concentrations of hormones, and the risk of breast cancer increased in G2548A, Q223R, K656N, and G276T polymorphisms. The effect of risk allele genotypes on serum concentration of hormones showed that changes in serum concentration of estrogen and leptin in all studied polymorphisms were associated with breast cancer in postmenopausal women. But adiponectin level was only affected by polymorphisms K109R, K656N, and G276 and G11391A. Conclusions: High BMI and genetic variation can affect cancer development by changing the serum concentrations of hormones in different genotypes. Studying various populations’ genetics and lifestyle can help definitive conclusions about genetics and obesity.

Relugolix/Estradiol/Norethisterone (Norethindrone) Acetate: A Review in Symptomatic Uterine Fibroids.

An oral fixed-dose combination of relugolix/estradiol/norethisterone (also known as norethindrone) acetate (Ryeqo®; Myfembree®) has been approved for the management of heavy menstrual bleeding associated with uterine fibroids in the USA and management of moderate to severe symptoms of uterine fibroids in the EU. Relugolix is a gonadotropin releasing hormone (GnRH) receptor antagonist that decreases serum estradiol and progesterone concentrations to postmenopausal levels. The addition of estradiol/norethisterone acetate to relugolix ameliorates relugolix-induced bone loss and hot flush. In the two phase 3 LIBERTY trials, relugolix + estradiol/norethisterone substantially decreased menstrual bleeding and improved a range of other uterine fibroid symptoms in women with uterine fibroids-associated heavy menstrual bleeding. The combination was generally well tolerated, with vasomotor symptoms being the most common adverse reaction. Treatment with this combination for over up to 2 years did not induce a clinically meaningful bone loss in the majority of women. Relugolix/estradiol/norethisterone acetate, with its convenient once-daily administration, is a useful addition to current pharmacological treatment options for premenopausal women with symptomatic uterine fibroids.

The Comparison the Impact of Flare-up GnRH Agonist with Delayed-Start GnRH Antagonist Protocols on the IVF Outcome of Poor Responder Patients: A Randomized Controlled Trial

Objectives: The current research was established to make a comparison between the delayed-start GnRH antagonist and flare-up GnRH agonist protocols in poor response patients. Methods: The present study is a randomized, prospective, controlled trial that was performed on 150 women who referred to two distinct in vitro fertilization (IVF) centers in Iran. Patients were randomly assigned to two experimental groups, as one group was treated with the delayed-start GnRH antagonist protocol (delayed-start group), while another group was treated with the flare-up protocol (flare-up group). Results: The serum concentrations of estradiol and progesterone, along with the thickness of endometrial tissue and the number of follicles ≥13 mm was significantly increased in the delayed-start group compared with the flare-up group. Also, the number of total oocytes, retrieved mature oocytes, total embryos, fertilized oocytes, as well as the quality of embryos were markedly higher in the delayed-start group when compared with the flare-up group. No statistically significant difference was found in the rates of fertilization, implantation, and pregnancy between the two experimental groups. Conclusions: According to the above evidence, it seems that the effect of delayed-start protocol on ovarian responsiveness was more pronounced during controlled ovarian stimulation in comparison with the flare-up protocol and the delayed start protocol probably lead to better implantation and pregnancy rates in comparison with the flare up agonist protocol cycle in poor responders.

Associations between Repeated Measures of Urinary Phthalate Metabolites with Hormones and Timing of Natural Menopause: The Study of Women&amp;#x27;s Health Across the Nation

Background and Aim: Studies on phthalate metabolites and sex hormones during the menopausal transition are limited and have yielded conflicting results. We aimed to examine the associations of phthalate metabolites with hormones including estradiol, testosterone, follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), anti-Müllerian hormone (AMH), and the timing of natural menopause. Methods: We examined 1,189 midlife women from the Study of Women’s Health Across the Nation aged 45-56 years in 1999-2000 who had complete information on phthalate metabolites and hormones while not receiving hormone therapy. Urinary concentrations of 12 phthalate metabolites were repeatedly measured in 1999-2000 and 2002-2003. Hormones were measured at the same time points. Linear mixed-effect models were used to calculate percent differences (%D) and 95% confidence intervals (CIs) in serum concentrations of estradiol, testosterone, FSH, SHBG, and AMH per doubling in urinary phthalate metabolites. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% CIs of natural menopause per doubling increase in urinary phthalate metabolites. Results: We observed significant associations of phthalate metabolites with lower testosterone concentrations: mono (7-carboxy-2-methyloctyl) phthalate (MCOP) (%D: -2.08%, 95% CI: -3.66, -0.47), and mono-n-butyl phthalate (MnBP) (%D: -1.99%, 95% CI: -3.82, -0.13), after adjusting for multiple comparisons with false discovery rates &amp;#x3c; 5%. Lower AMH concentrations were also found with higher MECPP (%D: -14.26%, 95% CI: -24.10, -3.14), MEHHP (%D: -15.58%, 95% CI: -24.59, -5.50), and MEOHP (%D: -13.50%, 95% CI: -22.93, -2.90). No associations were observed for other hormones or timing of natural menopause. Conclusions: These results suggest that exposure to phthalates may affect circulating levels of testosterone in midlife women. Exposure to phthalates may also dimmish the ovarian reserve. Given the endocrine-disrupting role of phthalates, future studies are warranted to evaluate their impact on health outcomes among midlife women. Keywords: Phthalates; endocrine-disrupting chemicals; hormones; midlife women; menopause

Nesfatin-1 as a potential marker for functional hypothalamic amenorrhea

Objective Nesfatin-1 plays an important role in regulating metabolism, appetite, gut motility, and eating behavior. It is suspected that abnormalities in nesfatin-1 secretion may be involved in the development of anorexia nervosa, and as such, this study aims to investigate the “circumstances of” nesfatin-1 in patients with functional hypothalamic amenorrhea (FHA). Materials and Methods One hundred and forty-seven patients with FHA were enrolled to the present study. A control group consisting of 88 healthy, age-matched subjects was used. Both study and control groups had blood samples drawn to establish baseline serum concentrations of luteinizing hormone, follicle-stimulating hormone, estradiol, prolactin, thyroid-stimulating hormone, fT4, morning cortisol, dehydroepiandrosterone sulfate, testosterone, glucose, and insulin. Nesfatin-1 was also measured with the use of enzyme-linked immunosorbent assay. Results Patients with FHA were found to have a significantly decreased concentration of serum nesfatin-1 when compared to healthy controls (6.21 ± 4.79 vs. 8.64 ± 6.63 respectively, p = 0.005). No statistically significant difference in nesfatin-1 levels was found between patients with normal and decreased BMI in the FHA group. Significant positive correlation was observed between serum nesfatin-1 concentration and 17-β-estradiol, while a significant negative correlation was observed between serum nesfatin-1 concentration and patient age, fasting glucose, and HDL levels. Conclusions This is the first known study to examine nesfatin-1 concentration in the context of clinical FHA. Patients with FHA were found to have decreased serum nesfatin-1 concentrations. This finding may prove instrumental in our future approach managing patients with FHA.

Influence Of The Menstrual Cycle On Muscle Damage Marker And Leukocyte Reaction Following Eccentric Exercise

PURPOSE:Ovarian hormone could inhibit exercise-induced muscle damage and leukocyte infiltration. Premenopausal women experience ovarian hormonal changes by the menstrual cycle (MC); therefore, MC could be related to muscle damage and leukocyte reaction, although it is not be clear. The purpose of this study was to investigate how MC could influence serum creatine kinase (CK) and leukocyte reaction following eccentric exercise. METHODS: Twenty-two untrained women with eumenorrhea (age 27.0 ± 6.4 years; height 160.1 ± 4.2 cm; weight 57.8 ± 7.0 kg; and body mass index 22.5 ± 2.3 kg/m2 [mean ± SD]) participated in the study. The subjects performed 10 sets of 6 repetitions of eccentric exercises with their nondominant arm in the early follicular phase (E-FP, n = 12) or midluteal phase (M-LP, n = 10). Blood samples were collected pre-exercise (PRE) and 4, 48, and 96 hours (h) post-exercise (POST) to analyze serum estradiol (E2) and progesterone (P4) concentration, serum CK, leukocyte count, and leukocyte fractionation (neutrophils, lymphocyte, monocyte, and other leukocytes). We assessed the isometric strength of elbow flexion, range of motion in the elbow joint, upper arm circumference and visual analog scale rating of perceived muscle soreness at PRE, immediately post, POST 4, 48, and 96 h. RESULTS: The serum E2 concentrations at PRE were significantly higher in the M-LP than the E-FP (E-FP 42.9 ± 18.6 vs. M-LP 186.4 ± 98.6 pg/mL; p < 0.01). The serum P4 concentrations at PRE were significantly higher in the M-LP than the E-FP (E-FP 0.2 ± 0.1 vs. M-LP 15.0 ± 3.1 ng/mL; p < 0.01). Significant time effects were present for serum CK at PRE to POST 48 h and 96 h (p < 0.05). No MC phase effect could be observed. The percent change in neutrophils at PRE to POST 4 h tended to be lower in the M-LP than the E-FP (E-FP 38.2 ± 32.6 vs. M-LP 11.4 ± 20.6%; p = 0.050). The serum E2 and P4 concentrations were not related to serum CK at all measurement points. A significant positive correlation could be observed between the PRE serum E2 concentration and PRE lymphocyte count (r = 0.470, p < 0.05). It was unrelated after the exercise. The POST 96 h serum CK was related to the POST 96 h neutrophil count (r = 0.469, p < 0.05). CONCLUSIONS: These results suggest that MC could affect the early leukocyte reaction following eccentric exercise without influencing the serum CK.

Methanol leaf extract of Abelmoschus caillei increased the serum levels of some hormones involved in follicule maturation in female Wister rats

There are ethnobotanical claims that the plant Abelmoschus caillei A.Chev. (Malvaceae) is beneficial for child bearing and in child labour. In fact, the inhabitants of Igboora town, South-West Nigeria claim the consumption of the leaf plays a role in the high incidences of multiple births experienced in the area. The study evaluated the effects of the methanol leaf extract of Abelmoschus caillei (MLAC) on some reproductive hormones involved in the maturation of graffian follicles of female wistar rats. The young leaves of authenticated Abelmoschus caillei plant were collected, air-dried, powdered and extracted with methanol. The extract (25, 50, 100, 200 and 400 mg/kg body weight, p.o.) was evaluated for its effects on the serum concentrations of oestradiol, lutenising hormone and follicle stimulating hormone using Enzyme Linked Immunosorbent Assay (ELISA) method. Clomiphene citrate was administered as standard drug. The analysis of the result showed that serum concentrations of the three hormones were significantly (P &lt; 0.05) higher at the administered doses compared with the negative control (distilled water) except at 25 mg/kg. The study concluded that Abelmoschus caillei A.Chev. (Malvaceae) significantly increased the serum conceentrations of LH, FSH and Oestradiol in female wistar rats and probably plays a role in the high incidences of multiple births observed in Igboora town in Nigeria.

Consumption of soy isoflavones during the prepubertal phase delays puberty and causes hypergonadotropic hypogonadism with disruption of hypothalamic-pituitary gonadotropins regulation in male rats

Isoflavones are phytoestrogens with recognized estrogenic activity but may also affect testosterone, corticosterone and thyroid hormone levels in experimental models. However, the molecular mechanisms involved in these alterations are still unclear. Isoflavones are present in soy-based infant formula, in breast milk after the consumption of soy by the mother and are widely used for the preparation of beverages consumed by toddlers and teenagers. In this sense, we proposed to investigate the effects of soy isoflavone exposure during the prepubertal period, a recognized window of sensitivity for endocrine disruption, over the hypothalamic-pituitary-testicular (HPT) axis. For this, 42 3-week-old male Wistar rats were exposed to 0.5, 5 or 50 mg of soy isoflavones/kg from postnatal day (PND) 23 to PND60. We evaluated body growth, age at puberty, serum concentrations of LH, FSH, testosterone and estradiol, and the expression of the transcripts (mRNA) of genes encoding key genes controlling the hypothalamic-pituitary-testicular (HPT) axis. In the hypothalamus, we observed an increase in Esr1 mRNA expression (0.5 and 5 mg). In the pituitary, we observed an increase in Gnrhr mRNA expression (50 mg), a reduction in Lhb mRNA expression (0.5 mg), and a reduction in Ar mRNA expression. In the testis, we observed an increase in Lhcgr mRNA expression (50 mg) and a reduction in Star mRNA expression (0.5 and 5 mg). The serum levels of LH (5 and 50 mg) and FSH (0.5 mg) were increased, while testosterone and estradiol were reduced. Puberty was delayed in all groups. Taken together, these results suggest that prepubertal consumption of relevant levels of soy isoflavones disrupts the HPT axis, causing hypergonadotropic hypogonadism and altered expression levels of key genes regulating the axis.

Impact of heat stress on follicular size, oestradiol concentration and oestrus expression in Nigerian Zebu cows

The study was conducted to evaluate the effect of heat stress on follicular size, oestradiol concentrations and oestrus expression in different seasons on Zebu cows. Twelve (n=12) matured, Zebu cows were utilized for over a year. The year was divided into 3 phases. Ambient temperature, relative humidity and rectal temperature were determined using. Cows were synchronized for oestrus. Ultrasonic follicular studies were carried out daily. Blood samples were collected after administration of a second dose of PFG2α to assess serum concentration of oestradiol. The enzyme-linked immunosorbent assay technique was used to determine the concentration of oestradiol. Oestrus activities were monitored by visual observation. Follicle diameters at 24 hr were lower (P&lt; 0.05) in the cold, dry season (6.34± 0.68 mm) than hot dry (8.09±0.52 mm) and the rainy season (8.62±0.9 mm). At 72 hr, follicular diameters were significantly higher P&lt;0.05 in the hot, dry season (17.01±1.41 mm) than cold dry (12.90±1.22 mm) and the rainy season (12.08±0.82 mm). Time to peak of oestradiol concentrations was shorter P&lt;0.05 in the cold, dry season (31.50±5.41 hr), followed by a hot, dry season (35.42±4.25 hr) and then rainy season (52.25±7.08 hr). The amplitude of oestradiol was higher P&lt;0.05 in the cold, dry season (39.13±5.27 pg/mL) than hot dry (19.50±2.52 pg/mL) and rainy seasons (17.63±1.89 pg/mL). Durations of proestrus oestradiol surges were significantly higher P&lt;0.05 in the rainy season (40.88±7.10 hr) followed by a hot, dry season (35.50±7.71 hr) and then cold dry season (24.25±3.27 hr.). The total number of mounting activities for two hr. was higher P&lt;0.05 in the cold, dry season (7.6±0.93/hr) followed by rainy season (6.2±1.28/hr) and then hot dry season (4.4±0.81/hr). In conclusion, the study showed that heat stress affected oestrus expression by lowering the number of mounts per hour, increasing follicular size and reducing oestradiol concentration of these cows.

Clinical and laboratory features in women with different phenotypes of polycystic ovary syndrome.

Misdiagnosis is still an obstacle in the workup of polycystic ovary syndrome. We compared patients' characteristics among phenotypes of the syndrome and assessed the association of the characteristics with oligo-anovulation, hyperandrogenism, and polycystic ovary. In the infertility department of a teaching hospital, we performed a cross-sectional study. Based on the Rotterdam Criteria, we included 136 patients with polycystic ovary syndrome and 46 healthy controls. The most common phenotype was A (N.=45;33%). Overall, A and C had larger Body Mass Index (P=0.019 and 0.030, respectively) and waist circumference (P=0.005 and 0.003) than control. Also, A and D had higher serum anti-mullerian hormone than control (both P<0.001) or phenotype C (P<0.001 and 0.01). Phenotypes A and C had higher insulin than control (both P=0.004). The highest level of estradiol was for control and the lowest for B. The lowest high-density lipoprotein was for C; and A to C phenotypes had higher triglyceride than control (P=0.002, <0.001, and 0.041). Larger body mass was associated with hyperandrogenism (adjusted Odds Ratio 95% CI=1.11 [1.01, 1.23], P=0.034); higher anti-mullerian hormone and high-density lipoprotein were related to oligo-anovulation (1.2 [1.07, 1.37], P=0.004; 1.1 [1.00, 1.13], P=0.041). Higher insulin and lower high-density lipoprotein were associated with polycystic ovary (1.11 [1.03, 1.21], P=0.013; 0.9 [0.82, 0.97], P=0.014). There are potentials in Body Mass Index, waist circumference, serum anti-mullerian hormone, insulin, estradiol, high-density lipoprotein, and triglyceride concentration for differentiating the phenotypes of polycystic ovary syndrome and for more precise diagnosis of hyperandrogenism, oligo-anovulation, and polycystic ovary morphology.

Relationship between serum vitamin D concentration and parameters of gonadal function in infertile male patients.

Vitamin D (vitD) deficiency could affect male reproductive function. Our objective was to investigate the relationship between serum vitD concentrations and hormonal and seminal parameters in infertile patients and to compare the results with those in healthy controls. Infertile patients (n = 29) and normozoospermic healthy donors (n = 27) were recruited for the study. Serum concentrations of vitD, total testosterone, estradiol, and sex hormone-binding globulin were determined using chemiluminescence assays, and free testosterone concentration was determined by radioimmunoassay. Semen analysis was performed as suggested by the World Health Organization. Statistical analysis was conducted using Student's t test, contingency tables, and linear regression studies. VitD concentrations were lower in patients than in controls (p < 0.001). A significant association (p < 0.001) was observed between vitD concentrations <20ng/mL and infertility. In the control group, significant correlations were reported between vitD concentrations >30 ng/mL and the concentrations of testosterone (p < 0.05), free testosterone (p < 0.01), and estradiol (p < 0.05). A direct correlation was found between vitD concentration and percentage of sperm vitality (p = 0.01). VitD also positively correlated with the percentage of progressive sperm motility (p <0.05) and sex hormone-binding globulin concentrations (p < 0.01). VitD may affect male reproductive parameters, and its deficiency could be associated with infertility.

Di-isononyl phthalate induces apoptosis and autophagy of mouse ovarian granulosa cells via oxidative stress

Di-isononyl phthalate (DINP) has been widely utilized in industrial, commercial and medical applications for the past few years. Therefore, more attention should be paid to the toxicity of DINP. DINP can cause damage to female reproductive system; however, the potential mechanism remains to be further investigated. In this study, female mice were orally administered with 0, 2, 20 and 200 mg DINP/kg/day for 14 days. We found that DINP significantly affected the arrangement of granulosa cells in ovarian follicles. In addition, DINP could induce apoptosis, autophagy and oxidative stress of the ovary tissue. Meanwhile, the serum estradiol concentration distinctly decreased in the 20 and 200 mg/kg DINP-treated groups, suggesting that DINP might affect the function of ovarian granulosa cells. Primary mouse ovarian granulosa cells were utilized for further investigation after the cells were treated with 0, 100, 200, 400 μM DINP for 24 h. Similar to the in vivo experiment, DINP could also induce apoptosis and autophagy of ovarian granulosa cells, as well as oxidative stress; while inhibition of oxidative stress by NAC could alleviate DINP-induced apoptosis and autophagy. Furthermore, inhibition of autophagy by 3-MA could also rescue the induction of apoptosis by DINP. Taken together, these results indicated that DINP induced apoptosis and autophagy of mouse ovarian granulosa cells via oxidative stress, and autophagy played a cytotoxic role in DINP-induced apoptosis.

Effects of the Sex Steroid Hormone Estradiol on Biofilm Growth of Cystic Fibrosis Pseudomonas aeruginosa Isolates.

Women with cystic fibrosis (CF) have a significantly lower life expectancy compared to men, which is indicated by an earlier impairment of lung function due to chronic colonization with biofilm formed by Pseudomonas aeruginosa. There is growing evidence that blood serum concentrations of the steroid sex hormone estradiol (E2) correlate with the occurrence of pulmonary exacerbations in CF but also play a role in the mucoid switch of P. aeruginosa. This study aims to shed light on possible microbiological reasons for sexual dimorphism in CF by investigating the influence of E2 on biofilm formation of P. aeruginosa CF isolates. For this purpose, 10 CF isolates of the respiratory tract derived from different CF patients have been treated with E2 in a microtiter plate biofilm model. Biofilms have been examined by crystal violet assays, field emission scanning electron microscopy (FE-SEM), 3D laser scanning microscopy (LSM), and quorum sensing (QS) reporter assays of the supernatants taken from biofilms. This allowed us to simultaneously investigate the effects of E2 on attached biofilm mass, biofilm ultrastructure, and QS activity. Upon E2 treatment, six out of 10 investigated CF isolates showed an increase of attached biofilm mass, whereas biofilms from two tested non-CF laboratory strains (PAO1 and ATCC19660) did not. Moreover, FE-SEM and 3D LSM analyses of the E2 responsive CF biofilms revealed ultrastructural remodeling of biofilm structure at different scales with increased formation of prominent biofilm spots, enhanced coverage with extracellular polymeric substance (EPS), and extended average surface roughness. QS activity measurements performed in biofilm supernatants via luminescence acyl homoserine lactone (AHL) reporter assays further showed that E2 treatment may also modulate QS signaling, as shown in an E2 sensitive CF isolate. Together, our results suggest the biofilm modulating effects of E2 on various clinical CF isolates that are documented by both biomass and ultrastructural changes of biofilms. The gained new insight into the influence of steroid hormones on P. aeruginosa biofilm phenotypes might pave the way for novel future approaches in personalized medicine based on the patients’ sex and hormonal status.

The value of serum estradiol concentration on the day of endometrial transformation in predicting the outcome of frozen-thawed embryo transfer in hormone replacement cycle

To analyze whether the serum concentration of estradiol on the day of progesterone conversion could predict the pregnancy outcome of frozen-thawed embryo transfer in hormone replacement cycle. In this paper, a case-control study was conducted to retrospectively analyze the 230 cycles of hormone replacement therapy-frozen thawed embryo transfer(HRT-FET)conducted by the Department of Reproductive Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University from January 2018 to December 2020. The concentration of serum estradiol was between 139.5-3 941.0 pg/ml. According to the percentile of serum estradiol concentration on the day of endometrial transformation, patients were divided into three groups: control group (<25th percentile, n=58), high estradiol group (25th-75th percentile, n=112) and ultra-high estradiol group (>75th percentile, n=60). Comparing the basic characteristics and pregnancy outcome of the three groups, the main observation index was the live birth rate, and the secondary observation index was the clinical pregnancy rate. F test and Kruskal-Wallis (H) test were used to compare the measurement data, and χ2 test was used to compare the counting data. The results showed that there was no significant difference in age, anti-Müllerian hormone(AMH), antral follicle count(AFC), body mass index(BMI), years of infertility and the proportion of primary infertility among the three groups(F=2.375, H=5.479, H=5.374, F=1.391, H=4.779, χ²=1.969, P>0.05). FET cycle treatment: There was no significant difference in the concentration of progesterone (P) before transformation, the thickness of endometrium on the day of transformation, the proportion of single embryo transfer and blastocyst transfer among the three groups (H=5.359, H=5.957, χ²=0.626, χ²=4.532, P>0.05). The days of estrogen administration before endometrial transformation in the three groups during the FET cycle were 13.0 (12.0, 14.0) days in the high estradiol group and 13.0 (12.0, 15.0) days in the ultra-high estradiol group, which were significantly longer than those in the control group 13.0(12.0, 13.3)days. The E2 concentration before intimal transformation in high estradiol group was 1 560.4 (1 170.2, 1 848.2) pg/ml, while that in ultra-high estradiol group was 2 420.9 (2 131.0, 2 849.2) pg/ml, which was significantly higher than that in control group 238.8 (206.9, 287.0) pg/ml. The pregnancy outcome of the three groups: the clinical pregnancy rate of the three groups was 37.9% in the control group, 51.8% in the high estradiol group and 40.0% in the ultra-high estradiol group, of which the high estradiol group had the highest clinical pregnancy rate, followed by the ultra-high estradiol group. But there was no significant difference among the three groups (χ²=3.853, P>0.05). The embryo implantation rate of the three groups was 19.3%, 25.0%, 32.8%, respectively, and the embryo implantation rate of the ultra-high estradiol group was the highest, but there was no significant difference among the three groups (χ²=5.544,P>0.05).The live birth rate of the three groups was 37.9%, 39.3%, 40.0%, respectively, and the difference was not statistically significant (χ²=0.05, P>0.05). A total of 14(13.5%) abortions occurred in 104 clinical pregnancies, all of which occurred in the high estradiol level group. Of the 104 clinical pregnancies, 24 (23.1%) had twin pregnancies, which occurred in the high estradiol level group (10 cases) and the ultra-high estradiol level group (14 cases). There were no twin pregnancies in the control group. Ectopic pregnancy occurred in 4 of 230 FET cycles (1.7%), 2 in control group and 2 in high estradiol group, and no ectopic pregnancy in ultra-high estradiol group.