Plasma Estradiol Research Articles

Increased number of large non-atretic follicles and co-dominance effects account for high litter sizes in Bonga sheep.

To understand the ovarian basis for prolificacy of Bonga sheep, a total of 31 ewes were selected based on litter size (LS) records and divided into two groups: High Prolificacy (HP) (n=20) with LS≥2 and Low Prolificacy (LP) (n=11) with LS=1. At a synchronized estrus, follicular dynamics were determined using transrectal ultrasonography. Plasma estradiol concentrations were also monitored. In total 27 ewes were observed in estrus being 9/11 LP (82%) and 18/20 HP (90%). On the day of estrus (day 0), the mean number of large follicles was higher (p<.05) in HP (1.78±0.19) than in LP (1.0±0.28) ewes. Prior to estrus, more (p<.05) medium follicles were visible for HP compared to LP ewes. Plasma estradiol concentrations were higher in HP compared to LP ewes (18.91±0.41 vs. 14.51±0.65pg/ml; p<.05) and similarly was ovulation number (2.3±0.15 vs. 1.28±0. 14; p<.05). Higher ovulation rates and litter size in Bonga sheep are evidenced by the previous presence of more large follicles and the existence of co-dominance effects as most likely medium follicles are selected to ovulate.

Application value of estradiol in seminal plasma in predicting semen parameters of male infertile patients

Objective To research the correlation between estradiol in seminal plasma and semen parameters of male infertile patients and to explore the value of seminal estradiol in predicting sperm quality. Methods A total of 86 infertility men who visited the reproductive center of our hospital from October to December 2018 were randomly selected and were measured semen parameters according to the WHO laboratory standard. We also tested seminal plasma estradiol by chemiluminescence. The patients were divided into four groups according to the seminal parameters: oligozoospermia (group 1, n=12), asthenospermia (group 2, n=24), oligoasthenozoospermia (group 3, n=24), normozoospermia (group 4, n=26). Results The level of estradiol in seminal plasma in group 1 to 4 were respectively (56.97±10.55) pg/ml, (52.30±8.64) pg/ml, (54.02±11.63) pg/ml, and (45.79±5.87) pg/ml, with statistically significant difference (P<0.01). The correlation analysis showed that the seminal plasma estradiol was negatively correlated with sperm concentration and sperm progressive motility, was not correlated with sperm normal morphology and sperm acrosin activity. The ROC curve of estradiol was drawn for the diagnosis of abnormal sperm. The cut off value of curve was 42.50 pg/ml, the sensitivity was 90.00%, the specificity 69.23%, the area under the curve was 0.737 (P<0.01), and the 95% confidence interval was (0.634, 0.840). Conclusion Seminal plasma E2 more than 42.50 pg/ml may be connected with abnormal sperm counts and vitality. Therefore, seminal plasma estradiol has certain forecastable value, which can be used as evaluation index of the diagnosis and treatment of male infertility patients. Key words: Estradiol; Sperm motility parameters; Sperm morphology; Acrosin

The effect of standard laboratory diets on estrogen signaling and spatial memory in male and female rats

Phytoestrogens are plant-derived compounds that can modulate estrogen activity in the brain and periphery. Laboratory rodent diets are typically high in soy-based phytoestrogens and therefore may influence neurophysiological and behavioural measures that are sensitive to estrogen signaling. Here we assessed such measures in rats (males and females) fed Australian made diets that varied in their soy levels. We found that a low-soy diet promoted greater weight, and lower levels of plasma estradiol, particularly in male rats. It also produced sex-specific effects on estrogen receptor gene expression in the brain, increasing ESR2 expression in the hippocampus and prefrontal cortex in female rats, and decreasing dopamine D1 receptor gene expression in the striatum of both male and female rats. We also found a dietary effect on short-term place recognition memory, but this was independent of soy levels in the diet. These results demonstrate that the choice of rodent laboratory diet can influence physiology, neurobiology and behavior, particularly on measures related to estrogen signaling.

Enrichment of imidacloprid and its metabolites in lizards and its toxic effects on gonads

Soil contaminants can cause direct harm to lizards due to their regular swallowing of soil particles. As the world’s fastest growing insecticide with long half-life in soil, the endocrine disrupting effect of neonicotinoids on lizards deserves more attention. In this report, we assessed the endocrine disrupting effect of imidacloprid on Eremias argus during 28 days of continuous exposure. Among the imidacloprid and its metabolites, only the metabolite 6-chloropyridic acid had a significant accumulation in the gonads and was positively correlated with its blood concentration. Imidacloprid might cause endocrine disrupting effects on lizards in two ways. First, the desnitro metabolites of imidacloprid could accumulate in the brain, inhibited the secretion of gonadotropin-releasing hormone, and ultimately affected the feedback regulation of hypothalamic-pituitary-gonadal related hormones. Secondly, imidacloprid severely inhibited the gene expression of the corresponding enzymes in the gonadal anti-oxidative stress system, causing histological damage to the gonads and ultimately affecting gonadal function. Specifically, exposure to imidacloprid resulted in abnormal arrangement of spermatogenic epithelial epithelium, hyperplasia of epididymal wall, and oligospermia of male lizard. Meanwhile, gene expressions of cyp17, cyp19, and hsd17β were severely inhibited in the imidacloprid exposure group, consistent with decreased levels of testosterone and estradiol in plasma. Imidacloprid exposure could cause insufficient androgen secretion and less spermatogenesis in male lizards. The risk of imidacloprid exposure to female lizards was not as severe as that of male lizards, but it still inhibited the expression of cyp19 in the ovaries and led to a decrease in the synthesis of estradiol. This study firstly reported the endocrine disruption of imidacloprid to lizards, providing new data for limiting the use of neonicotinoids.

Blocking of Estradiol Receptors ERα, ERβ and GPER During Development, Differentially Alters Energy Metabolism in Male and Female Rats

Estradiol not only participates in the regulation of energy metabolism in adulthood, but also during the first stages of life as it modulates the alterations induced by under- and over-nutrition. The objectives of the present study were to determine: 1) If estradiol is involved in the normal programming of energy metabolism in rats; 2) If there is a specific window of time for this programming and 3) If males and females are differentially vulnerable to the action of this hormone. Estrogen receptors (ER) α, ERβ and GPER were blocked by their specific antagonists MPP, PHTPP and G15, respectively, from postnatal day (P) 1 (the day of birth) to P5 or from P5 to P13. Physiological parameters such as body weight, fat depots and caloric intake were then analysed at P90. Hypothalamic AgRP, POMC, MC4R, ERα, ERβ and GPER mRNA levels and plasma levels of estradiol, were also studied. We found that blocking ER receptors from P5 to P13 significantly decreases long-term body weight in males and hypothalamic POMC mRNA levels in females. The blocking of ERs from P1 to P5 only affected plasma estradiol levels in females. The present results indicate programming actions of estradiol from P5 to P13 on body weight in male and POMC expression in female rats and emphasize the importance of including both sexes in metabolic studies. It is necessary to unravel the mechanisms that underlie the actions of estradiol on food intake, both during development and in adulthood, and to determine how this programming differentially takes place in males and females.

156 Oestrus response, corpus luteum function, and pregnancy rates following aromatase inhibitor treatment in beef heifers

In a previous study involving the use of the aromatase inhibitor letrozole to synchronise ovulation, incomplete luteolysis appeared to confound the synchronising effect in letrozole-treated heifers. Experiments were done to determine whether letrozole treatment interferes with luteolysis and affects the timing of oestrus (Experiment 1) and whether pregnancy rate is affected by the stage of the oestrous cycle during which letrozole treatment is initiated (Experiment 2). In Experiment 1, Hereford heifers were fitted with a HeatWatch sensor and given prostaglandin F2α (PGF2α). Ovulation (Day 0) was determined by daily ultrasonography, and on Day 3 heifers were given an intravaginal letrozole-releasing device or a sham device for 4 days (n=16 per group). Half of the heifers in each group were given PGF2α on Day 7 (PGF 1×) or on Day 7 and 7.5 (PGF 2×). Ultrasonography and blood sampling were done daily from device insertion to removal, every 12h for 72h following PGF2α and daily for 14 days following ovulation. In Experiment 2, heifers were randomly assigned to three groups (n=10-11 per group) in which a 4-day letrozole-releasing device treatment was initiated during metoestrus (Days 0-2), diestrus (Days 7-9), or pro-oestrus (Days 15-17). Prostaglandin F2α was given at device removal and again 12h later. Heifers were inseminated with frozen-thawed semen and given gonadotrophin-releasing hormone 66h after device removal. Ultrasonography and blood sampling were done twice daily from device removal until ovulation. End points examined included dominant follicle and corpus luteum (CL) diameters, onset of oestrus, and plasma concentrations of oestradiol determined by radioimmunoassay. Nominal data were compared using GENMOD, analysis of variance, or mixed model for repeated-measures and were expressed as means±s.e.m. Proportional data were analysed using chi-square. In Experiment 1, no main effects or interactions were detected between device or PGF treatment for onset of oestrus following PGF2α (overall 60.0±2.5h) or CL diameter profiles during luteolysis. Residual variation was reduced in the timing of the first PGF to ovulation in the PGF 2× group versus the PGF 1× group (5.6±2.2h vs. 15.2±3.2 h; P&amp;lt;0.01). The CL diameter following ovulation was greater in the PGF 2× group compared with the PGF 1× group (P=0.03). Circulating plasma oestradiol during treatment was greater (P=0.04) in both the PGF 1× and sham groups. In Experiment 2, a greater proportion of heifers in the pro-oestrus group ovulated ≤24h after device withdrawal compared with the metoestrus and diestrus groups combined (6/11 vs. 0/22, respectively; P&amp;lt;0.05). Pregnancy rate tended to be greater in the metoestrus group than in the diestrus group (10/11 vs. 6/10; P=0.08), and pregnancy rate in both groups was greater than that in the pro-oestrus group (0/11; P&amp;lt;0.05). In conclusion, letrozole treatment did not interfere with luteolysis, and PGF2α given 2× at a 12-h interval on Day 7 after ovulation decreased variance in the timing to ovulation. Treatment initiated during metoestrus and diestrus yielded greater pregnancy rates than that started during pro-oestrus and warrants efficacy testing in a large fixed-time AI field trial. This research was supported by Alberta Agriculture and Forestry and by Dechra.

Characterization of gene expression in the hypothalamo-pituitary-gonadal axis during the preovulatory surge in the turkey hen

ABSTRACTA preovulatory surge (PS) of luteinizing hormone (LH) and progesterone triggers follicle ovulation, which is the first step of egg production and is orchestrated by the hypothalamo-pituitary-gonadal (HPG) axis. In the HPG axis, hypothalamic peptides, gonadotropin releasing hormone, and gonadotropin inhibitory hormone, control the production of follicle stimulating hormone and LH by the pituitary, which subsequently regulate ovarian production of estradiol and progesterone, respectively. The goal of this study was to characterize the HPG axis function of average egg producing hens by assessing plasma hormone profiles and hypothalamic, pituitary, and follicle gene expression outside and during the PS (n = 3 per group). Results were analyzed by a one-way ANOVA using the mixed models procedure of SAS. Plasma estradiol was not affected by the PS (P > 0.05), but plasma progesterone levels increased 8-fold during the PS when compared to basal progesterone levels (P < 0.05). HPG axis gene expression related to ovulation stimulation (e.g., GNRH, GNRHR, and LHB) was down-regulated during the PS; whereas gene expression related to follicle development (e.g., FSHB) was up-regulated during the PS. Additionally, in the hypothalamus and pituitary, estradiol receptor expression was up-regulated during the PS, whereas progesterone receptor expression was down-regulated during the PS. In the follicle cells, gene expression pertaining to progesterone (e.g., STAR), androgen (e.g., HSD17B1), and estradiol (e.g., CYP19A1) production was up-regulated during the PS. Prior to this study, the HPG axis had yet to be characterized during the PS in the turkey hen. This study showed that the PS significantly impacted gene expression in the hypothalamus, pituitary, and ovarian follicles. These results provide a foundation for further research into the regulation of ovulation and egg production in turkey hens.

The effects of early life adversity on growth, maturation, and steroid hormones in male and female rats.

Early life adversity is a risk factor for psychiatric disorders, yet the mechanisms by which adversity increases this risk are still being delineated. Here, we used a limited bedding and nesting (LBN) manipulation in rats that models a low resource environment to examine effects on growth, developmental milestones, and endocrine endpoints. In LBN, dams and pups, from pups' postnatal days 2-9, are exposed to an environment where dams lack proper materials to build a nest. This manipulation is compared to control housing conditions, where rat dams have access to ample nesting materials and enrichment throughout pups' development. We found that the LBN condition altered maternal care, increasing pup-directed behaviors while reducing self-care. This, perhaps compensatory, increase in nursing and attention to pups did not mitigate against changes in metabolism, as LBN reduced weight gain in both sexes and this effect persisted into adulthood. Although adult stress hormone levels in both sexes and vaginal opening and estrous cycle length in females were not disrupted, there was other evidence of endocrine dysregulation. Compared to controls, LBN rats of both sexes had shortened anogenital distances, indicating reduced androgen exposure. LBN males also had higher plasma estradiol levels in adulthood. This combination of results suggests that LBN causes a demasculinizing effect in males that could contribute to lasting changes in the brain and behavior. Importantly, alterations in metabolic and endocrine systems due to early life adversity could be one mechanism by which stress early in life increases risk for later disease.

Postnatal Feeding With a Fat Rich Diet Induces Precocious Puberty Independent of Body Weight, Body Fat, and Leptin Levels in Female Mice.

Puberty generally occurs when an individual has stored a sufficient amount of energy. Previous reports have shown that postnatal overfeeding, induced by a small litter size or maternal high fat diet (HFD) feeding during gestation and lactation increases body weight (BW), body fat, plasma leptin levels, and induces precocious puberty. The role of BW, body fat, and leptin in postnatal HFD-induced precocious puberty is poorly understood. In this study, we investigated if postnatal HFD feeding induces precocious puberty independent of BW, body fat, and leptin levels. Different litter sizes and different exposure time to HFD were used to produce HFD feeding pups with different BW and body fat. BW, body fat, and plasma hormones levels were checked at different time points to test their relation with HFD-induced precocious puberty. Our results showed that postnatal HFD feeding increases BW, body fat, adipocyte size, and induces precocious puberty. HFD-induced precocious puberty was independent of BW, body fat, and plasma leptin levels. Plasma gonadotrophin, estradiol, testosterone and insulin levels were comparable in most of the groups. Our results collectively suggest that postnatal HFD feeding induces precocious puberty independent of BW, body fat and plasma leptin levels. Our results also suggest that HFD feeding acts as a stimulator for puberty onset but further studies are needed to understand how it induces precocious puberty.

Effect of photoperiod on ovarian maturation in Cheirodon interruptus (Teleostei: Characidae).

Cheirodon interruptus is a ubiquitous small characid that inhabits the Pampean region and commonly used as bait. Its vast market is supplied from the wild population causing a significant environmental impact. In this study, we assess the effect of photoperiod on ovarian maturation in order to evaluate its potential as a tool to manipulate reproduction under artificial conditions. Four treatments in triplicate (light: dark, L: D) were tested: 24L: 0D, 12L: 12D, 0L: 24D and a progressive photoperiod corresponding to the daily photoperiod increments in wild during winter-spring transition, accelerated three times. The experiment was conducted for 45 days. Gonadosomatic index (GSI), oocyte mean diameter, vitellogenic oocyte proportions, plasma estradiol concentrations (E2), condition factor (Kn) and standard length were estimated. Values of mean GSI, oocyte diameter, vitellogenic oocyte proportions and E2 concentration were maximum in the progressive treatment indicating vitellogenesis stimulation. In turn the same parameters were minimum in the 24L: 0D, revealing the vitellogenesis inhibition. This study showed that photoperiodic regime play an important role in the onset of ovarian maturation in C. interruptus.

Transgender women on oral HIV pre-exposure prophylaxis have significantly lower tenofovir and emtricitabine concentrations when also taking oestrogen when compared to cisgender men.

IntroductionOral HIV Pre‐Exposure Prophylaxis (PrEP) with tenofovir (TFV) disoproxil fumarate (TDF)/emtricitabine (FTC) is highly effective. Transgender women (TGW) have increased HIV risk, but have been underrepresented in trials. For TGW on oestrogens for gender‐affirming hormone treatment (GAHT), TDF/FTC‐oestrogen interactions may negatively affect HIV prevention or gender‐affirming goals. Our aim was to evaluate any pharmacokinetic drug‐drug interaction between GAHT and TDF/FTC.MethodsWe performed a pharmacokinetic study, in an urban outpatient setting in 2016 to 2018, of the effects of GAHT on TFV, FTC and the active forms TFV diphosphate (TFV‐DP) and FTC triphosphate (FTC‐TP) in eight TGW and eight cisgender men (CGM). At screening, participants were HIV negative. TGW were to maintain their GAHT regimens and have plasma oestradiol concentrations >100 pg/mL. Under direct observation, participants took oral TDF/FTC daily for seven days. At the last dose, blood was collected pre‐dose, one, two, four, six, eight and twenty‐four hours, and colon biopsies were collected at 24 hours to measure drug concentration. TGW versus CGM concentration comparisons used non‐parametric tests. Blood and colon tissue were also obtained to assess kinase expression.ResultsPlasma TFV and FTC C24 (trough) concentrations in TGW were lower by 32% (p = 0.010) and 32% (p = 0.038) respectively, when compared to CGM. Plasma TFV and FTC 24‐hr area under the concentration‐time curve in TGW trended toward and was significantly lower by 27% (p = 0.065) and 24% (p = 0.028) respectively. Peak plasma TFV and FTC concentrations, as well as all other pharmacokinetic measures, were not statistically significant when comparing TGW to CGM. Oestradiol concentrations were not different comparing before and after TDF/FTC dosing. Plasma oestrogen concentration, renal function (estimated creatinine clearance and glomerular filtration rate), and TFV and FTC plasma concentrations (trough and area under the concentration‐time curve) were all correlated.ConclusionsGAHT modestly reduces both TFV and FTC plasma concentrations. In TGW taking GAHT, it is unknown if this reduction will impact the HIV protective efficacy of a daily PrEP regimen. However, the combination of an on demand (2 + 1 + 1) PrEP regimen and GAHT may result in concentrations too low for reliable prevention of HIV infection.

Sex differences in progression of diabetic nephropathy in OVE26 type 1 diabetic mice

AimsOVE26 mice (FVB background), genetically overexpressing calmodulin in pancreatic beta cells, develop early onset type 1 diabetes, leading to progressive diabetic nephropathy (DN), with features of established human DN. The role of gender in characteristics of renal lesions has remained unexplored. MethodsMale and female OVE26 mice were compared to age and sex matched wild-type, nondiabetic FVB mice at ages of 4, 12, 24 and 36 weeks. Nephropathy was examined by measuring urine albumin-to-creatinine ratio, histopathology, expression of pathological markers and immunochemistry in the same cohort of mice. ResultsProgression of diabetic kidney disease was evident first in the OVE26 glomerulus, initially as mesangial matrix expansion at 4 weeks followed by loss of podocytes, glomerular volume expansion and severe albuminuria at 12 weeks. Tubule dilation and initiation of interstitial fibrosis did not become significant until 24 weeks. T-lymphocyte infiltration into the renal parenchyma appeared at 36 weeks. OVE26 female mice developed more advanced DN than male OVE26 mice, such as more severe albuminuria, greater podocyte loss, additional fibrosis and significantly more inflammatory cell infiltration. The female OVE26 mice had lowest level of plasma estradiol in all 36 weeks old mice, as well as renal estrogen receptors. ConclusionsThis demonstration of the role of gender, combined with the detailed characterization of DN progression illustrates the value of OVE26 mice for understanding gender effects on DN and provides the basis for researchers to better select the age and sex of OVE26 mice in future studies of type 1 DN. Research in contextWhat is already known about this subject?•OVE26 mice, genetically overexpressing calmodulin in pancreatic beta cells, develop early onset type 1 diabetes.•OVE26 mice are a widely used and valuable rodent model which develop severe, progressive diabetic nephropathy, with features of established human diabetic nephropathy.What is the key question?•Does gender play a role in determining characteristics of renal lesions and severity of nephropathy?What are the new findings?•Female OVE26 mice had more severe albuminuria, greater podocyte loss.•Female OVE26 mice had additional fibrosis and significantly more inflammatory cell infiltration.•Diabetes induced reductions in estradiol levels and renal estrogen receptors may be responsible for the female sensitization to DN in OVE26 mice.How might this impact on clinical practice in the foreseeable future?•Our findings provide the basis for researchers to better select the age and sex of OVE26 mice in future studies of type 1 DN.

Dysregulation of endocrine disruption, apoptosis and the transgenerational toxicity induced by spirotetramat

Spirotetramat (SPT) is a new tetronic acid derivative insecticide used to control scales and aphids; the potential for endocrine disruptor effects in fish could not be finalized with the available data. In this study, zebrafish were selected to assess the endocrine-disrupting effects. Significant decrease of plasma estradiol (E2), testosterone (T) and 11-ketotestosterone (11-KT) were observed in both male and female following the spirotetramat exposure; the vitellogenin (VTG) level in females significantly decreased. The expression of the hypothalamic-pituitary-gonad (HPG) axis genes fshr, lhr and esr1 showed significant increase in the gonads, which expression in males is higher than in females. In addition, the activities of capspase-3 and caspase-9 significantly decreased in both males and females liver, while the capspase-3 and caspase-9 were increased in male testis, the mRNA expression levels of genes expression related to the apoptosis pathway were also significantly altered after the spirotetramat exposure. Additionally, we found the parental zebrafish exposed to spirotetramat induced the development delay of its offspring. Above all, the adverse effects induced by spirotetramat suggesting that spirotetramat is a potential exogenous hazardous agent.

Evaluation of molt induction using cassava meal varying the length of feeding period in older (90 week) laying hens.

Physiological changes during molt and postmolt egg production variables were compared among hens induced to molt by using cassava meal varying the length of the feeding period. Hens were randomly assigned to 3 treatments of 72 birds each: 1) molted by full feeding with cassava meal for 4 wk (CAS4); 2) molted by full feeding with cassava meal for 5 wk (CAS5); and 3) molted by full feeding with cassava meal for 6 wk (CAS6). All groups were fed a pullet developer diet for 2 wk following treatment. During the molt period, the birds were exposed to an 8L:16D photoperiod and had access to drinking water at all times. Thereafter, all hens were fed a layer diet (17.71% CP), and exposed to a 16L:8D photoperiod, and production performance was measured for 16 wk. The molt treatments resulted in total cessation of egg production in all treatments within 2 wk following feeding of the molt diet. BW loss of birds in the CAS6 treatment was approximately 41.81%, which was significantly higher (P < 0.05) than those in the CAS5 (37.63%) and CAS4 (31.89%) treatments. The CAS5 and CAS6 hens had significantly lower (P < 0.05) ovarian and oviducal weights than the CAS4 hens. No consistent differences were observed for concentrations of plasma estradiol and progesterone, bone quality, or mortality among the treatments. Postmolt feed consumption, egg weight, and mortality were not different (P > 0.05) as a result of molt induction method. However, the CAS4 hens had significantly higher (P < 0.05) cumulative egg production and lower feed conversion ratio than hens in the CAS6 treatment. Significant differences were found among treatments for Haugh units and shell thickness in some periods of the postmolt. It was concluded that cassava meal could be used to induce molt in laying hens effectively, feeding the molt diet for 4 wk produced optimum body weight loss and postmolt performance.

Anti-Osteoporotic Effect of Soy Isoflavones Intake on Low Bone Mineral Density Caused by Voluntary Exercise and Food Restriction in Mature Female Rats.

Female athlete triad (FAT) is an interrelationship between menstrual dysfunction, low energy availability with or without eating disorder, and decreased bone mineral density (BMD) in female athletes. The purpose of this study was to investigate whether isoflavone intake can prevent bone loss caused by voluntary wheel running under energy-restricted condition. We used a female rat model of osteoporosis for female athletes established previously. Fourteen female Sprague-Dawley rats (8-wk old) were fed ad libitum and had free access to wheels throughout the study. At 18 wk of age, the rats were divided randomly into the following groups: 1) running control (RC), 2) running energy restriction (RR), and 3) running energy restriction and isoflavone-fed (RR+Iso) groups. The RR group was 30% dietary restricted. The RR+Iso group was 30% dietary restricted and fed the diet containing 0.5% isoflavone powder (Fujiflavone P40). The experimental period lasted 31 wk. At the end of this experiment, BMD of the proximal femur in the RR group was significantly lower than that in the RC group. However, the BMD in the RR+Iso group was not significantly different from that in the RC group. Moreover, the plasma estradiol (E2) level in the RR and RR+Iso groups was significantly lower than that in the RC group. These findings suggest that isoflavone intake inhibited bone loss when the E2 level was low in female mature rat model. Our findings may reveal the possible novel role of isoflavone in osteoporosis among female athletes.

Transcriptomic analysis reveals potential mechanisms of toxicity in a combined exposure to dibutyl phthalate and diisobutyl phthalate in zebrafish (Danio rerio) ovary

Phthalate esters (PAEs), which are notable plasticizers, can be prolific contaminants in aquatic environments, and have been shown to induce reproductive toxicity. However, the studies concerning their toxicity towards aquatic species are based on individual chemicals, and the combined toxicity of PAEs to aquatic organisms remains unclear. The aim of this study was to explore the potential toxicity mechanisms associated with combined exposure to dibutyl phthalate (DBP) and diisobutyl phthalate (DiBP) in adult female zebrafish ovaries. Zebrafish were exposed to DBP, DiBP and their mixtures for 30 days, and their effects on ovarian histology, plasma sex hormones and ovarian transcriptomics were investigated. Plasma estradiol (E2) levels were significantly decreased by 38.9% in the DBP-1133 exposure group and 41.0% in the DiBP-1038 exposure group. The percentage of late/mature oocytes was also significantly decreased by 17.3% under DBP-1133 exposure and 16.2% under DiBP-1038 exposure, while that under combined exposure was not significantly affected. Nevertheless, transcriptome sequencing revealed 2564 differentially expressed genes (DEGs) in zebrafish ovaries after exposure to the mixtures. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the DEGs were involved in the neuroactive ligand-receptor interaction, GnRH, progesterone-mediated oocyte maturation, oocyte meiosis and steroid hormone biosynthesis signaling pathways. These results revealed that combined exposure exerts potential reproductive toxicity at the molecular level.

Endogenous Circadian Regulation of Female Reproductive Hormones.

Studies suggest that female reproductive hormones are under circadian regulation, although methodological differences have led to inconsistent findings. To determine whether circulating levels of reproductive hormones exhibit circadian rhythms. Blood samples were collected across ∼90 consecutive hours, including 2 baseline days under a standard sleep-wake schedule and ∼50 hours of extended wake under constant routine (CR) conditions. Intensive Physiological Monitoring Unit, Brigham and Women's Hospital. Seventeen healthy premenopausal women (22.8 ± 2.6 years; nine follicular; eight luteal). Fifty-hour CR. Plasma estradiol (E2), progesterone (P4), LH, FSH, SHBG, melatonin, and core body temperature. All hormones exhibited significant 24-hour rhythms under both standard sleep-wake and CR conditions during the follicular phase (P < 0.05). In contrast, only FSH and SHBG were significantly rhythmic during the luteal phase. Rhythm acrophases and amplitudes were similar between standard sleep-wake and CR conditions. The acrophase occurred in the morning for P4; in the afternoon for FSH, LH, and SHBG; and during the night for E2. Our results confirm previous reports of ∼24-hour rhythms in many female reproductive hormones in humans under ambulatory conditions but demonstrate that these hormones are under endogenous circadian regulation, defined as persisting in the absence of external time cues. These results may have important implications for the effects of circadian disruption on reproductive function.

Estrogen Receptor-β Mediates Estradiol-Induced Pregnancy-Specific Uterine Artery Endothelial Cell Angiotensin Type-2 Receptor Expression.

The pregnancy-augmented uterine vasodilation is linked to increased AT2R (angiotensin type-2 receptor) that mediates the vasodilatory effects of angiotensin II. However, the mechanisms controlling AT2R expression during pregnancy remain unclear. Estrogens are known to play a role in vascular adaptations during pregnancy. We hypothesized that estrogen stimulates uterine artery AT2R expression via ER (estrogen receptor)-β-dependent transcription in a pregnancy-specific endothelium-dependent manner. Plasma estradiol levels increased and peaked in late pregnancy and returned to prepregnant levels post-partum, correlating with uterine artery AT2R and ERβ upregulation. Estradiol stimulated AT2R mRNA expression in endothelium-intact but not endothelium-denuded late pregnant and nonpregnant rat uterine artery ex vivo. Consistently, estradiol stimulated AT2R mRNA expression in late pregnant but not nonpregnant primary human uterine artery endothelial cells in vitro, which was abolished by ER antagonist ICI 182,780. Higher ERα protein bound to ER-responsive elements in AT2R promoter in the nonpregnant arteries whereas higher ERβ bound in the pregnant state. ERα protein levels were similar but higher ERβ protein levels were expressed in pregnant versus nonpregnant human uterine artery endothelial cells. Estradiol stimulation recruited ERα to the AT2R promoter in the nonpregnant state and ERβ to the AT2R promoter in pregnancy; however, only ERβ recruitment mediated transactivation of the AT2R reporter gene in pregnant human uterine artery endothelial cells. Estradiol-induced AT2R expression was abolished by the specific ERβ (not ERα) antagonist 4-[2-Phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]phenol (PHTPP) and mimicked by the specific ERβ (not ERα) agonist 2,3-bis(4-Hydroxyphenyl)-propionitrile (DPN) in pregnant human uterine artery endothelial cells in vitro. This study demonstrates a novel role of pregnancy-augmented ERβ in AT2R upregulation in the uterine artery and provides new insights into the mechanisms underlying uterine vascular adaptation to pregnancy.

Relationships of Sex Hormone Levels with Activity of Daily Living in Chinese Female Centenarians.

Activity of daily living declines in female elderly, which not only increases hospitalization and mortality rates, but also aggravates individual and societal burden. Large samples are needed to elucidate the relationships of plasma sex hormone levels with activity of daily living in Chinese female centenarians to better understand the effects of hormone-replacing therapy. As the first time in the world, the current study was designed to investigate the relationships of plasma sex hormone levels with activity of daily living in Chinese female centenarians. China Hainan Centenarian Cohort Study was carried out in 18 cities and counties of Hainan Province. Home interview, physical examination and blood analysis were carried out in 583 female centenarians following standard procedures. Barthel Index was used to assess the activity of daily living. Median age of all female centenarians was 102 years, with the range from 100 to 115 years. Median values of Barthel Index were 85(60-90). In multivariate linear regression analyses, Barthel Index values were inversely associated with plasma luteinizing hormone (LH), follicle-simulating hormone (FSH), testosterone, progesterone and estradiol levels (P<0.05 for all). Plasma sex hormone levels, including LH, FSH, testosterone, progesterone and estradiol, had significant relationships with activity of daily living in Chinese female centenarians.

Role of ovarian sympathetic nerves and cholinergic local system during cold stress.

An increase in the sympathetic tone in the rat ovary induces a polycystic ovary (PCOS-like) phenotype. No information exists about its impact on fertility. In contrast, increased follicular development and improved fertility in rats were found after pharmacological inhibition of acetylcholinesterase, which increased intraovarian acetylcholine (ACh). Now, we studied the impact of sympathetic stress, followed by a recovery period without stress, on the cholinergic and noradrenergic systems of the rat ovary and on fertility. To activate ovarian sympathetic nerves, female Sprague-Dawley rats were exposed to cold stress (4°C/3 h day for 28 days; first period), followed by a 28-day period without cold stress (second period). No changes in estrous cyclicity during the first period was found. At the end of this period, ovarian levels of NA and ACh were increased. Morphometric analysis showed lower numbers of secondary and antral follicles, enhanced follicular atresia and fewer corpora lutea. Plasma progesterone was lower and testosterone was higher than that in controls. At end of the second period, ovarian ACh levels had returned to control levels, but NA levels remained elevated. The second period was also characterized by the presence of cystic follicles in the ovary, by elevated plasma testosterone and estradiol levels, while progesterone levels were decreased. Estrous cyclicity and ovulation during that period were irregular and fertility decreased. Thus, cold stress initially activated both ovarian noradrenergic and cholinergic system. After stress, the ovary did not fully recover and activation of the noradrenergic system persisted and correlated with cystic ovarian morphology and decreased fertility.