FEATURES OF BLOOD PRESSURE DAILY MONITORING INDICATORS, STRUCTURAL AND FUNCTIONAL CHANGES OF THE LEFT VENTRICLE AND VESSELS IN WOMEN WITH HYPERTENSION II STAGE OF DIFFERENT REPRODUCTIVE AGE AND THEIR RELATIONSHIP WITH SEX HORMONES LEVEL.

Arterial hypertension (AH) ranks first among diseases of the cardiovascular system. The severity of clinical manifestations and prognosis in patients with AH is determined not only by the level of increased blood pressure (BP) but also by the degree of target organ damage. The aim - to evaluate indicators of daily BP monitoring, and structural and functional changes of the left ventricle and blood vessels in women with stage II hypertension of different reproductive age and to determine their relationship with the level of sex hormones. The study included 114 women with essential arterial hypertension II stage, I-II-degree, chronic heart failure 0-I degree of different reproductive age. Ambulatory blood pressure monitoring (24-h ABPM), the echocardiological examination, determination of the vascular function, and the level of sex hormones were performed in patients. It was noted that the process of reproductive aging is associated with the deterioration of BP parameters in women with AH. It was established that the process of reproductive aging of women suffering from AH and progressive hypoestrogenemia are associated with the deepening of a whole series of unfavorable changes in the structural and functional state of the heart and blood vessels. In the process of reproductive aging in women with AH, not only a decrease in the level of estradiol was determined, but also higher numbers of both systolic and diastolic BP, which led to a greater load of pressure on the heart as a target organ and more pronounced structural and functional changes. The process of reproductive aging is associated with the deterioration of BP parameters in women with AH. Extinction of reproductive function and progressive hypoestrogenemia in women with AH were associated with higher BP, increased mass of the myocardium of the left ventricular, progression of its diastolic filling disorder and deterioration of the vasoregulatory function of blood vessels.

Sexual dimorphism in skin immunity is mediated by an androgen-ILC2-dendritic cell axis.

Males and females exhibit profound differences in immune responses and disease susceptibility. However, the factors responsible for sex differences in tissue immunity remain poorly understood. Here, we uncovered a dominant role for type 2 innate lymphoid cells (ILC2s) in shaping sexual immune dimorphism within the skin. Mechanistically, negative regulation of ILC2s by androgens leads to a reduction in dendritic cell accumulation and activation in males, along with reduced tissue immunity. Collectively, our results reveal a role for the androgen-ILC2-dendritic cell axis in controlling sexual immune dimorphism. Moreover, this work proposes that tissue immune set points are defined by the dual action of sex hormones and the microbiota, with sex hormones controlling the strength of local immunity and microbiota calibrating its tone.

Associations of glyphosate exposure and serum sex steroid hormones among 6-19-year-old children and adolescents.

Glyphosate, ranked as one of the most widely used herbicides in the world, has raised concerns about its potential disruptive effects on sex hormones. However, limited human evidence was available, especially for children and adolescents. The present study aimed to examine the associations between exposure to glyphosate and sex hormones among participants aged 6-19 years, utilizing data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2016. Children and adolescents who had available data on urinary glyphosate, serum sex steroid hormones, including testosterone (TT), estradiol (E2) and sex hormone binding globulin (SHBG), and covariates were selected. Additionally, the ratio of TT to E2 (TT/E2) and the free androgen index (FAI), which was calculated using TT/SHBG, were also included as sex hormone indicators. Survey regression statistical modeling was used to examine the associations between urinary glyphosate concentration and sex hormone indicators by age and sex group. Among the 964 participants, 83.71% had been exposed to glyphosate (>lower limit of detection). The survey regression revealed a marginally negative association between urinary glyphosate and E2 in the overall population, while this association was more pronounced in adolescents with a significant trend. In further sex-stratified analyses among adolescents, a significant decrease in E2, FAI, and TT (p trend <0.05) was observed in female adolescents for the highest quartile of urinary glyphosate compared to the lowest quartile. However, no similar association was observed among male adolescents. Our findings suggest that exposure to glyphosate at the current level may decrease the levels of sex steroids in adolescents, particularly female adolescents. Considering the cross-sectional study design, further research is needed to confirm our findings.

Higher number of steps is related to lower endogenous progesterone but not estradiol levels in women.

OBJECTIVES: Sex steroid hormones are important not only for reproduction but also for many aspects of women's health, including the risk of breast cancer. Physical activity has been shown to influence sex hormone levels in women. This study aimed to investigate a relationship between the average daily number of steps and the sex hormone (estradiol and progesterone) levels in premenopausal women. MATERIALS AND METHODS: Data were collected from 85 healthy, urban women of reproductive age who performed at least 180 minutes/week of moderate physical activity for two complete menstrual cycles. Physical activity was measured using wrist bands. Estradiol and progesterone concentrations were measured in daily-collected saliva samples in the second menstrual cycle. RESULTS: There was a significant negative association between the average number of steps taken daily and salivary progesterone levels after adjusting for potential confounding factors (age, BMI). Women who took more than 10,000 steps a day had significantly lower progesterone levels compared to women who took less than 10,000 steps. The association between physical activity and estradiol levels was statistically insignificant. DISCUSSION: Our results indicate that taking at least 10,000 steps a day reduces progesterone levels, but this intensity of physical activity may not be high enough to affect estradiol levels. Daily step tracking is a valuable element of health promotion, but currently recommended levels of physical activity may not be high enough for healthy premenopausal women to significantly reduce both sex hormone levels and thus their risk of postmenopausal breast cancer.

Developmental and adult stress: effects of steroids and neurosteroids.

In humans, exposure to early life adversity has profound implications for susceptibility to developing neuropsychiatric disorders later in life. Studies in rodents have shown that stress experienced during early postnatal life can have lasting effects on brain development. Glucocorticoids and sex steroids are produced in endocrine glands and the brain from cholesterol; these molecules bind to nuclear and membrane-associated steroid receptors. Unlike other steroids that can also be made in the brain, neurosteroids bind specifically to neurotransmitter receptors, not steroid receptors. The relationships among steroids, neurosteroids, and stress are multifaceted and not yet fully understood. However, studies demonstrating altered levels of progestogens, androgens, estrogens, glucocorticoids, and their neuroactive metabolites in both developmental and adult stress paradigms strongly suggest that these molecules may be important players in stress effects on brain circuits and behavior. In this review, we discuss the influence of developmental and adult stress on various components of the brain, including neurons, glia, and perineuronal nets, with a focus on sex steroids and neurosteroids. Gaining an enhanced understanding of how early adversity impacts the intricate systems of brain steroid and neurosteroid regulation could prove instrumental in identifying novel therapeutic targets for stress-related conditions.

Association between sex hormones and bone age in boys aged 9-18 years from China.

This study aimed to analyse the association between sex hormones and bone age (BA) in boys aged 9-18 years, both individually and interactively, and further to explore whether nutritional status may influence this association. A retrospective analysis was performed among 1382 Chinese boys with physical measurements, sexual characteristics, BA radiographs and sex hormone indicators from February 2015 to February 2022. A total of 470 (34.0%) boys had advanced BA. BA was positively associated with estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone in both advanced and normal BA groups after adjusting for age, genetic height and body mass index. Multiple logistic regression showed that after adjusting for covariates, estradiol (odds ratio [OR] = 1.66, 95% confidence interval [CI]: 1.14-2.12), LH (OR = 1.43, 95% CI: 1.04-1.96), and testosterone (OR = 1.58, 95% CI: 1.17-2.13) were significantly associated with the increased risk of advanced BA in boys, and the association was reinforced when these hormones were interactively explored. Stratified by nutritional status, the interaction between estradiol, LH, and testosterone showed a strong association with advanced BA in boys with normal weight.

Sex-Biased Expression and Response of microRNAs in Neurological Diseases and Neurotrauma.

Neurological diseases and neurotrauma manifest significant sex differences in prevalence, progression, outcome, and therapeutic responses. Genetic predisposition, sex hormones, inflammation, and environmental exposures are among many physiological and pathological factors that impact the sex disparity in neurological diseases. MicroRNAs (miRNAs) are a powerful class of gene expression regulator that are extensively involved in mediating biological pathways. Emerging evidence demonstrates that miRNAs play a crucial role in the sex dimorphism observed in various human diseases, including neurological diseases. Understanding the sex differences in miRNA expression and response is believed to have important implications for assessing the risk of neurological disease, defining therapeutic intervention strategies, and advancing both basic research and clinical investigations. However, there is limited research exploring the extent to which miRNAs contribute to the sex disparities observed in various neurological diseases. Here, we review the current state of knowledge related to the sexual dimorphism in miRNAs in neurological diseases and neurotrauma research. We also discuss how sex chromosomes may contribute to the miRNA sexual dimorphism phenomenon. We attempt to emphasize the significance of sexual dimorphism in miRNA biology in human diseases and to advocate a gender/sex-balanced science.

[Weight gain during menopause: physiology and practical implications]. / Prise de poids pendant la ménopause : physiologie et implications pratiques.

Fluctuations in sex hormones at different stages of reproductive life, such as the menopausal transition, have been suggested as players in weight regulation. Indeed, the transition from a predominantly estrogenic state to an androgenic state characteristic of the menopausal transition contributes to changes in body composition with accumulation of fat and simultaneous loss of lean mass. However, whether these changes contribute to the weight gain remains debatable. Other physiological and psychosocial factors come into play. It is therefore important to offer individualized support with the objective to minimize the risk of weight gain and associated complications.

La fluctuation des hormones sexuelles à différentes étapes de la vie reproductive, telles que la transition ménopausique, a été proposée comme une des composantes de la régulation de poids. Effectivement, le passage d'un état principalement œstrogénique à un état androgénique, caractéristique de la transition ménopausique, contribue à des modifications de la composition corporelle avec une accumulation de graisse et une perte simultanée de masse maigre. Cependant, la question de savoir si ces changements contribuent à une prise de poids reste discutable. L'obésité est une maladie multifactorielle et d'autres facteurs d'ordre physiologique et psychosociaux rentrent en jeu. Il est donc important d'offrir un accompagnement individualisé aux femmes concernées pour les aider à minimiser le risque de prise pondérale et des complications associées.

Decreased levels of sex hormones in females with solitary pulmonary nodules were risk factors for malignancy.

OBJECTIVE: The purpose of this research was to detect the relationship between the levels of sex hormones in females with solitary pulmonary nodules (SPNs) and their potential malignancies. METHODS: A total of 187 consecutive patients with pathologically confirmed SPNs by chest CT were enrolled in our study. They were divided into two groups based on the pathologic findings of SPNs after surgery: benign and malignant SPNs. Progesterone (P), estradiol (E2), and testosterone (T) levels in the two groups were measured. Meanwhile, we used binary logistic regression analysis to analyze the risk factors for SPNs. RESULTS: Of these 187 patients, 73 had benign SPNs, while 114 had malignant SPNs. We found that the levels of progesterone (P), estradiol (E2), and testosterone (T) were decreased significantly in patients with malignant SPNs compared to patients with benign SPNs (all P < 0.05). Multivariate logistic regression analysis revealed that second-hand smoke, burr sign, lobulation sign, pleural traction sign, vascular convergence sign, vacuole sign, and ≥ 1 cm nodules were independent risk factors for malignant pulmonary nodules in females. CONCLUSIONS: Decreased levels of sex hormones in females were associated with malignant pulmonary nodules, suggesting that they can contribute to the diagnosis of lung cancer.

Postprandial glucose variability and clusters of sex hormones, liver enzymes, and cardiometabolic factors in a South African cohort of African ancestry.

INTRODUCTION: This study aimed to, first, determine the clusters of sex hormones, liver enzymes, and cardiometabolic factors associated with postprandial glucose (PPG) and, second to evaluate the variation these clusters account for jointly and independently with polygenic risk scores (PRSs) in South Africans of African ancestry men and women. RESEARCH DESIGN AND METHODS: PPG was calculated as the integrated area under the curve for glucose during the oral glucose tolerance test (OGTT) using the trapezoidal rule in 794 participants from the Middle-aged Soweto Cohort. Principal component analysis was used to cluster sex hormones, liver enzymes, and cardiometabolic factors, stratified by sex. Multivariable linear regression was used to assess the proportion of variance in PPG accounted for by principal components (PCs) and type 2 diabetes (T2D) PRS while adjusting for selected covariates in men and women. RESULTS: The T2D PRS did not contribute to the PPG variability in both men and women. In men, the PCs' cluster of sex hormones, liver enzymes, and cardiometabolic explained 10.6% of the variance in PPG, with PC1 (peripheral fat), PC2 (liver enzymes and steroid hormones), and PC3 (lipids and peripheral fat) contributing significantly to PPG. In women, PC factors of sex hormones, cardiometabolic factors, and liver enzymes explained a similar amount of the variance in PPG (10.8%), with PC1 (central fat) and PC2 (lipids and liver enzymes) contributing significantly to PPG. CONCLUSIONS: We demonstrated that inter-individual differences in PPG responses to an OGTT may be differentially explained by body fat distribution, serum lipids, liver enzymes, and steroid hormones in men and women.

The impact of PTSD on associations between sex hormones and cardiovascular disease symptoms.

Background: Women have twice the lifetime prevalence of posttraumatic stress disorder (PTSD) relative to men, and PTSD is a known risk factor for cardiovascular disease (CVD). Two sex hormones - estradiol and progesterone - have been found to impact both PTSD and CVD symptomatology, but the way in which sex hormones influence cardiovascular physiology among individuals with PTSD is not well understood.Objective: This study sought to clarify the association between sex hormones, PTSD, and CVD among trauma-exposed women.Method: Sixty-six trauma-exposed women (M age = 31.45, SD = 8.92) completed a clinical interview for PTSD and self-reported CVD symptoms; estradiol and progesterone were assayed from blood samples. The association between each sex hormone and CVD symptoms was analyzed, controlling for age, systolic blood pressure (BP), and diastolic BP.Results: Neither estradiol nor the PTSD-by-estradiol interaction was significantly associated with CVD symptoms. Higher progesterone and, relatedly, progesterone-to-estradiol ratio (PE ratio) were each significantly associated with greater CVD symptom severity, but only for individuals with lower relative PTSD severity.Conclusions: The findings indicate that PTSD moderates the relationship between progesterone and CVD symptoms, and further research is warranted to reconcile findings in existing literature regarding the direction of and mechanisms behind this relationship.

Posttraumatic stress disorder (PTSD) is a risk factor for cardiovascular disease (CVD) and sex hormones have been implicated in their link.The current study examined associations between sex hormones, PTSD, and CVD symptoms among 66 trauma-exposed women.Estradiol was not significantly associated with CVD symptoms, but higher progesterone was significantly associated with greater CVD symptom severity, but only for individuals with lower relative PTSD severity.

XX sex chromosome complement modulates immune responses to heat-killed Streptococcus pneumoniae immunization in a microbiome-dependent manner.

BACKGROUND: Differences in male vs. female immune responses are well-documented and have significant clinical implications. While the immunomodulatory effects of sex hormones are well established, the contributions of sex chromosome complement (XX vs. XY) and gut microbiome diversity on immune sexual dimorphisms have only recently become appreciated. Here we investigate the individual and collaborative influences of sex chromosome complements and gut microbiota on humoral immune activation. METHODS: Male and female Four Core Genotype (FCG) mice were immunized with heat-killed Streptococcus pneumoniae (HKSP). Humoral immune responses were assessed, and X-linked immune-related gene expression was evaluated to explain the identified XX-dependent phenotype. The functional role of Kdm6a, an X-linked epigenetic regulatory gene of interest, was evaluated ex vivo using mitogen stimulation of B cells. Additional influences of the gut microbiome on sex chromosome-dependent B cell activation was also evaluated by antibiotically depleting gut microbiota prior to HKSP immunization. Reconstitution of the depleted microbiome with short-chain fatty acid (SCFA)-producing bacteria tested the impact of SCFAs on XX-dependent immune activation. RESULTS: XX mice exhibited higher HKSP-specific IgM-secreting B cells and plasma cell frequencies than XY mice, regardless of gonadal sex. Although Kdm6a was identified as an X-linked gene overexpressed in XX B cells, inhibition of its enzymatic activity did not affect mitogen-induced plasma cell differentiation or antibody production in a sex chromosome-dependent manner ex vivo. Enhanced humoral responses in XX vs. XY immunized FCG mice were eliminated after microbiome depletion, indicating that the microbiome contributes to the identified XX-dependent immune enhancement. Reconstituting microbiota-depleted mice with select SCFA-producing bacteria enhanced fecal SCFA concentrations and increased humoral responses in XX, but not XY, FCG mice. However, exposure to the SCFA propionate alone did not enhance mitogenic B cell stimulation in ex vivo studies. CONCLUSIONS: FCG mice have been used to assess sex hormone and sex chromosome complement influences on various sexually dimorphic traits. The current study indicates that the gut microbiome impacts humoral responses in an XX-dependent manner, suggesting that the collaborative influence of gut bacteria and other sex-specific factors should be considered when interpreting data aimed at delineating the mechanisms that promote sexual dimorphism.

Male and female immune systems differ in their ability to respond to infectious challenge. While males tend to be more susceptible to infection and produce lower amounts of antibodies in response to vaccination, females are more prone to develop autoimmune and inflammatory diseases. Key contributors to these differences include sex hormones, sex chromosome complement (XX in females vs. XY in males), and distinct gut microbial communities capable of regulating immune activation. While each factor has been studied individually, this research underscores the potential for these factors to collaboratively impact immune activation. Here, possession of an XX vs. XY sex chromosome complement was demonstrated to enhance antibody responses to heat-killed Streptococcus pneumoniae vaccination. While attempting to determine the underlying cause of this immune enhancement, the gut microbiome was identified to play a critical role. In the absence of an intact gut microbiome, XX immune activation was reduced to levels similar to those seen in XY sex chromosome complement-possessing mice. Replacement of the depleted gut microbiomes with select SCFA-producing bacterial species enhanced SCFA levels in antibiotic-treated mice and rescued the XX-dependent immune enhancement, suggesting a SCFA-mediated contribution. Further studies are needed to determine exactly how these select bacteria impact immune activation in a sex chromosome complement-dependent manner. Our findings highlight the need to consider the collaborative effects of individual sex-specific factors when attempting to understand immune sex biases, as a better understanding of these interactions will likely pave the way for improving therapeutics and vaccines tailored to both sexes.

Reproductive endocrine disruption effect and mechanism in male zebrafish after life cycle exposure to environmental relevant triclosan.

Triclosan (TCS) is a wide-spectrum antibacterial agent that is found in various water environments. It has been reported to have estrogenic effects. However, the impact of TCS exposure on the reproductive system of zebrafish (Danio rerio) throughout their life cycle is not well understood. In this study, zebrafish fertilized eggs were exposed to 0, 10, and 50 µg/L TCS for 120 days. The study investigated the effects of TCS exposure on brain and testis coefficients, the expression of genes related to the hypothalamus-pituitary-gonadal (HPG) axis, hormone levels, vitellogenin (VTG) content, histopathological sections, and performed RNA sequencing of male zebrafish. The results revealed that life cycle TCS exposure had significant effects on zebrafish reproductive parameters. It increased the testis coefficient, while decreasing the brain coefficient. TCS exposure also led to a decrease in mature spermatozoa and altered the expression of genes related to the HPG axis. Furthermore, TCS disrupted the balance of sex hormone levels and increased VTG content of male zebrafish. Transcriptome sequencing analysis indicated that TCS affected reproductive endocrine related pathways, including PPAR signaling pathway, cell cycle, GnRH signaling pathway, steroid biosynthesis, cytokine-cytokine receptor interaction, and steroid hormone biosynthesis. Protein-protein interaction (PPI) network analysis confirmed the enrichment of hub genes in these pathways, including bub1bb, ccnb1, cdc20, cdk1, mcm2, mcm5, mcm6, plk1, and ttk in the brain, as well as fabp1b.1, fabp2, fabp6, ccr7, cxcl11.8, hsd11b2, and hsd3b1 in the testis. This study sheds light on the reproductive endocrine-disrupting mechanisms of life cycle exposure to TCS.

Comprehensive evaluation of inactivated SARS-CoV-2 vaccination on sperm parameters and sex hormones.

Background: The inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine has made significant contributions to fighting the epidemic in the past three years. However, the rapid development and application raised concerns about its safety in reproductive health, especially after several studies had observed a decrease in semen parameters following two doses of mRNA SARS-CoV-2 vaccination. Thus, it is necessary to comprehensively evaluate the effect of inactivated SARS-CoV-2 vaccine on male fertility. Methods: A retrospective cohort study was conducted in the Center for Reproductive Medicine of the Affiliated Hospital of Jining Medical University between July 2021 and March 2023. A total of 409 men with different vaccination status and no history of SARS-CoV-2 infection were included in this study. Their sex hormone levels and semen parameters were evaluated and compared separately. Results: The levels of FSH and PRL in one-dose vaccinated group were higher than other groups, while there were no significant changes in other sex hormone levels between the control and inactivated SARS-CoV-2 vaccinated groups. Most semen parameters such as volume, sperm concentration, total sperm count, progressive motility and normal forms were similar before and after vaccination with any single dose or combination of doses (all P > 0.05). Nevertheless, the total motility was significantly decreased after receiving the 1 + 2 doses of vaccine compared to before vaccination (46.90 ± 2.40% vs. 58.62 ± 2.51%; P = 0.001). Fortunately, this parameter was still within the normal range. Conclusion: Our study demonstrated that any single dose or different combined doses of inactivated SARS-CoV-2 vaccination was not detrimental to male fertility. This information could reassure men who want to conceive after vaccination and be incorporated into future fertility recommendations.

Effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus (COVID-19) vaccination on male fertility.

Coronavirus disease 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains an ongoing global public health challenge. This disease causes damage not only to the respiratory system, affecting the normal physiological function of the lungs, but also to other vital organs, such as the heart and testicles. Existing studies have shown that co-expression of angiotensin-converting enzyme 2 and transmembrane serine protease 2 is the main mechanism by which SARS-CoV-2 invades host cells. Angiotensin-converting enzyme 2-expressing cells are widespread in the corpus cavernosum, reproductive tract and testis of men, which has raised concerns. Furthermore, abnormal sex hormone levels and decreased semen parameters were observed in coronavirus disease 2019 patients. This study comprehensively assessed the effects of SARS-CoV-2 infection on the testis, semen parameters, sex hormone levels and erectile function, and discussed possible transmission routes during sexual intercourse and the effect of vaccination on male fertility.

Effect of Bakri balloon tamponade combined with different suture methods on preventing postpartum hemorrhage in women with pregnancy-induced hypertension undergoing cesarean delivery.

OBJECTIVE: To investigate the effect of Bakri balloon tamponade (BBT) combined with different suture methods on preventing postpartum hemorrhage in women with pregnancy-induced hypertension (PIH) undergoing cesarean delivery (CD). METHODS: This randomized, double-blind, controlled trial was conducted at The First Affiliated Hospital of Xingtai Medical College from October 2020 to June 2023. Patients with PIH who had persistent bleeding after CD and were unresponsive to uterine contractions, sutures, or uterine disconnection procedures were eligible participants. Eligible participants were randomly assigned to control and study groups, with 50 patients in each group. The control group used BBT combined with B-lynch uterine compression sutures, while the study group used BBT combined with modified Hayman suture. Intraoperative and postoperative bleeding and changes in vital signs were compared between the 2 groups. Moreover, changes in inflammation levels, coagulation function, and sex hormone levels were compared between the 2 groups before and after surgery. RESULTS: A total of 122 patients with persistent bleeding after CD were recruited, of whom 22 were excluded (16 cases of uterine contractions and/or local uterine myometrial sutures for hemostasis, 4 cases of preoperative uterine artery embolization, and 2 cases of uterine malformations). The intraoperative blood loss, postoperative blood loss at 2 hours, postoperative blood loss at 24 hours, and decrease in red blood cell and hemoglobin in the study group were significantly lower than those in the control group (P < .05). After surgery, the levels of inflammation, coagulation function, and sex hormone in both groups improved compared to before surgery, and the study group was significantly better than the control group (P < .05). In addition, the incidence of postoperative adverse events in the study group was significantly lower than that in the control group (P < .05). CONCLUSIONS: The hemostatic effect of BBT combined with B-lynch uterine compression sutures is comparable to that of BBT combined with modified Hayman suture for postpartum hemorrhage in pregnant women with PIH undergoing CD, but the latter has less blood loss, attenuated inflammatory response, reduced impact on coagulation function and ovarian function, and a lower incidence of adverse events.

The Level of Sex Hormones and Corticosterone in Female Rats during Modeling of Visceral Obesity, Subsequent Physical Activity, and Normalization of the Diet.

The effects of diet-induced visceral obesity and non-drug options of its correction on the level of sex hormones and corticosterone were evaluated in 84 female Wistar rats. During stage I, the rats received either a standard diet (STD) or a high-calorie diet (HCD) for 8 weeks. During stage II, the animals were divided into subgroups depending on obesity correction: without correction (STD control and HCD), transition from HCD to STD (HCD/STD) and/or physical activity (treadmill exercise) for the next 8 weeks (HCD/STD+exercise, STD+exercise, and HCD+exercise). Diet-induced visceral obesity resulted in hyperandrogenization and increased blood corticosterone levels in females. Transition from HCD to STD regardless of physical activity led to normalization of testosterone level and, accordingly, to return to the functional norm of estrogen-androgen balance. The positive effect of moderate physical activity on hormonal status is realized only against the background of a balanced diet or during the transition from HCD to STD.

Liraglutide improved the reproductive function of obese mice by upregulating the testicular AC3/cAMP/PKA pathway.

BACKGROUND: The incidence of male reproductive dysfunction is increasing annually, and many studies have shown that obesity can cause severe harm to male reproductive function. The mechanism of male reproductive dysfunction caused by obesity is unclear, and there is no ideal treatment. Identification of effective therapeutic drugs and elucidation of the molecular mechanism involved in male reproductive health are meaningful. In this study, we investigated the effects of the GLP-1 receptor agonist liraglutide on sex hormones, semen quality, and testicular AC3/cAMP/PKA levels in high-fat-diet-induced obese mice. METHODS: Obese mice and their lean littermates were treated with liraglutide or saline for 12 weeks. Body weight was measured weekly. Fasting blood glucose (FBG) was measured using a blood glucose test strip. The serum levels of insulin (INS), luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T), free testosterone (F-TESTO), estradiol (E2), and sex hormone binding globulin (SHBG) were detected using ELISA. The sperm morphology and sperm count were observed after Pap staining. The mRNA and protein expression levels of testicular GLP-1R and AC3 were measured by RT-qPCR and Western blot, respectively. Testicular cAMP levels and PKA activity were detected using ELISA. RESULTS: Liraglutide treatment can decrease body weight, FBG, INS, HOMA-IR, E2 and SHBG levels; increase LH, FSH, T, and F-TESTO levels; increase sperm count; decrease the sperm abnormality rate; and increase GLP-1R and AC3 expression levels and cAMP levels and PKA activity in testicular tissue. CONCLUSIONS: Liraglutide can improve the sex hormone levels and semen quality of obese male mice. In addition to its weight loss effect, liraglutide can improve the reproductive function of obese male mice, which may also be related to the upregulation of AC3/cAMP/PKA pathway in the testis. This work lays the groundwork for future clinical studies.

Prenatal phthalate exposure and sex steroid hormones in newborns: Taiwan Maternal and Infant Cohort Study.

BACKGROUND: Newborn anogenital distance (AGD) has been associated with prenatal exposure of phthalates. The association between prenatal phthalate exposure and sex steroid hormones in newborns is unclear. OBJECT: This study aimed to examine whether cord-blood sex hormone levels were associated with prenatal phthalate exposure and newborn anogenital distance (AGD). METHODS: In the Taiwan Maternal and Infant Cohort Study, we recruited 1,676 pregnant women in their third trimester in 2012-2015 in Taiwan. We determined 11 urinary phthalate metabolites in pregnant women, three maternal and five cord-blood steroid sex-hormone concentrations. Five hundred and sixty-five mother-infant pairs with sufficient data were included. Trained neonatologists measured 263 newborns' AGD. We examined the associations of prenatal phthalate metabolite levels with AGD and hormones using linear regression models and evaluated correlations between maternal and cord-blood sex hormone levels and AGD. RESULTS: Compared with the male newborns exposed to maternal phthalate metabolites at the first tertile, AGD was -3.75, -3.43, and -3.53 mm shorter among those exposed at the median tertile of di-2-ethylhexyl phthalate (DEHP) metabolites, monobenzyl phthalate (MBzP), and monomethyl phthalate (MMP), respectively. Compared with those who had exposed at the first tertile, cord-blood follicle-stimulating hormone (FSH) decreased among male newborns exposed at higher levels of MMP, mono-n-butyl phthalate (MnBP), MBzP and DEHP, and among female newborns exposed at higher levels of MMP, MBzP and mono(2-ethyl-5-hydroxyhexyl) phthalate. However, we did not observe significant correlations of maternal or cord-blood sex steroid hormones with newborns' AGDs. CONCLUSIONS: Alterations in cord-blood sex steroid hormone levels were associated with prenatal phthalate exposures, particularly in male newborns. Women aspiring to be pregnant should be alerted of the need of reducing phthalate exposure.

Changes in fecal microbiota during estrous cycle in healthy thoroughbred mares.

Gut microbiota plays a crucial role in various physiological processes, including the regulation of the reproductive system and steroid sex hormones. Throughout the normal estrous cycle of healthy mares, the levels of estradiol-17ß (E2) and progesterone (P4) in the blood exhibit periodic changes. To investigate the relationship between cyclic changes in steroid sex hormones and the gut microbiome of mares, we analyzed the fecal microbiota composition in healthy mares during the typical estrous cycle. Blood and fecal samples from five healthy mares were collected, E2 and P4 levels in serum were analyzed using radioimmunoassay (RIA), and the gut microbiome was analyzed by 16S rRNA sequencing. The overall richness and composition of the gut microbiota remained relatively stable during the normal estrous cycle in mares. The Linear Discriminant Analysis Effect Size analysis of the microbial composition during the follicular and luteal phases identified the Rhodococcus genus as differentially abundant. These findings indicate that the mare's gut microbiota's significant composition remains consistent throughout the estrous cycle. At the same time, specific low-abundance pathogenic bacteria exhibit changes that align with sexual hormonal fluctuations.