Association Between the Oxidative Balance Score and Endometriosis: A Population-Based Study.

Purpose: To investigate the association between the oxidative balance score (OBS) and endometriosis. Methods: This cross-sectional study used four cycles of the National Health and Nutrition Examination Survey (NHANES) (1999-2000, 2001-2002, 2003-2004, and 2005-2006). OBS involved 16 dietary nutrients and 4 lifestyle factors, including 5 pro-oxidants and 15 anti-oxidants. According to weighted quartiles, the OBS was divided into four categories: < 12.54, 12.54-18.70, 18.71-24.68, and > 24.68. Endometriosis was diagnosed based on a question from the reproductive health questionnaire. Weighted multivariate logistic analysis was used to investigate the association between OBS and endometriosis. Subgroup analysis was performed based on menstrual regularity and female hormone use. Results: A total of 5095 women were included, with 1140 (22.37%), 1232 (24.18%), 1224 (24.02%), and 1499 (29.42%) women in the OBS < 12.54, of 12.54-18.70, of 18.71-24.68, and > 24.68 categories, respectively. After adjusting age, race, family poverty-to-income ratio (PIR), education level, uterine fibroids, menstrual regularity, oophorectomy, female hormone use, hypertension, dyslipidemia, and steroid drug, a high OBS (> 24.68) was found to be associated with lower odds of endometriosis [odds ratio (OR) = 0.70, 95% confidence interval (CI): 0.50-0.97, P = 0.033] compared to a low OBS (< 12.54). The similar result was also found in women with irregular menstruation (OR = 0.58, 95% CI: 0.37-0.91, P = 0.020) and with female hormone use (OR = 0.71, 95% CI: 0.52-0.98, P = 0.037). Conclusion: A high OBS was associated with lower odds of endometriosis, especially in women with irregular menstruation and female hormone use.

The effects of female sex hormones on the human cornea across a woman's life cycle.

The cornea is a hormone-responsive tissue that responds to changing levels of female sex hormones. This review focuses on the structural and functional changes in the human cornea associated with the hormonal milestones of menarche, pregnancy, and menopause, as well as consequences stemming from the use of exogenous sex hormones for fertility control and replacement. Articles were identified by searching PubMed without language or region restrictions. The primary outcomes evaluated were changes in central corneal thickness (CCT), intraocular pressure (IOP), and quality of the ocular tear film. The potential impact of hormone-associated changes on the diagnosis and surgical management of common eye diseases, as well as the potential use of sex hormones as therapeutic agents is also considered. Understanding the physiological effects of female sex hormones on the cornea is important because that knowledge can shape the management decisions physicians and women face about ocular health across their life stages.

Sex differences and the effect of female sex hormones on auditory function: a systematic review.

Aims: First, to discuss sex differences in auditory function between women and men, and whether cyclic fluctuations in levels of female sex hormones (i.e., estradiol and progesterone) affect auditory function in pre-menopausal and post-menopausal women. Second, to systematically review the literature concerning the discussed patterns in order to give an overview of the methodologies used in research. Last, to identify the gap in knowledge and to make recommendations for future work. Methods for the systematic review: Population, Exposure, Control, Outcome and Study design (PECOS) criteria were used in developing the review questions. The review protocol follows the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and was pre-registered in the Prospective Register of Systematic Reviews (PROSPERO; CRD42020201480). Data Sources: EMBASE, PubMed, MEDLINE (Ovid), PsycINFO, ComDisDome, CINAHL, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL) via Cochrane Library, and scanning reference lists of relevant studies, and internet resources (i.e., Mendeley) were used. Only studies published between 1999 and 2022, in English, or in English translation, were included. The quality of evidence was assessed using the Newcastle-Ottawa Scale (NOS). Results: Sex differences: Women had more sensitive hearing (measured at the level of peripheral and central auditory system) than men. Cyclic fluctuations: Auditory function in women fluctuated during the menstrual cycle, while no such fluctuations in men over the same time period were reported. Hearing sensitivity improved in women during the late follicular phase, and decrease during the luteal phase, implying an effect of female sex hormones, although the specific effects of estradiol and progesterone fluctuations on the central auditory system remain unclear. Hearing sensitivity in women declined rapidly at the onset of menopause. Conclusion: The review has shown the following. Consistent sex differences exist in auditory function across the auditory pathway with pre-menopausal women often showing better function than age-matched men. Moreover, pre-menopausal women show fluctuations in hearing function across the menstrual cycle with a better function during the peak of estradiol or when the ratio of estradiol to progesterone is high. Third, menopause marks the onset of hearing loss in women, characterized by a rapid decline in hearing sensitivity and a more pronounced loss than in age-matched men. Finally, the systematic review highlights the need for well-designed and -controlled studies to evaluate the influence of estradiol and progesterone on hearing by consistently including control groups (e.g., age-matched man), using objective tests to measure hormonal levels (e.g., in saliva or blood), and by testing participants at different points across the menstrual cycle. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020201480, identifier CRD42020201480.

Association of Polymorphisms in FSHR, INHA, ESR1, and BMP15 with Recurrent Implantation Failure.

Recurrent implantation failure (RIF) refers to two or more unsuccessful in vitro fertilization embryo transfers in the same individual. Embryonic characteristics, immunological factors, and coagulation factors are known to be the causes of RIF. Genetic factors have also been reported to be involved in the occurrence of RIF, and some single nucleotide polymorphisms (SNPs) may contribute to RIF. We examined SNPs in FSHR, INHA, ESR1, and BMP15, which have been associated with primary ovarian failure. A cohort of 133 RIF patients and 317 healthy controls consisting of all Korean women was included. Genotyping was performed by Taq-Man genotyping assays to determine the frequency of the following polymorphisms: FSHR rs6165, INHA rs11893842 and rs35118453, ESR1 rs9340799 and rs2234693, and BMP15 rs17003221 and rs3810682. The differences in these SNPs were compared between the patient and control groups. Our results demonstrate a decreased prevalence of RIF in subjects with the FSHR rs6165 A>G polymorphism [AA vs. AG adjusted odds ratio (AOR) = 0.432; confidence interval (CI) = 0.206-0.908; p = 0.027, AA+AG vs. GG AOR = 0.434; CI = 0.213-0.885; p = 0.022]. Based on a genotype combination analysis, the GG/AA (FSHR rs6165/ESR1 rs9340799: OR = 0.250; CI = 0.072-0.874; p = 0.030) and GG-CC (FSHR rs6165/BMP15 rs3810682: OR = 0.466; CI = 0.220-0.987; p = 0.046) alleles were also associated with a decreased RIF risk. Additionally, the FSHR rs6165GG and BMP15 rs17003221TT+TC genotype combination was associated with a decreased RIF risk (OR = 0.430; CI = 0.210-0.877; p = 0.020) and increased FSH levels, as assessed by an analysis of variance. The FSHR rs6165 polymorphism and genotype combinations are significantly associated with RIF development in Korean women.

A cocktail probe approach to evaluate the effect of hormones on the expression and activity of CYP enzymes in human hepatocytes with conditions simulating late stage of pregnancy.

PURPOSE: Pregnancy-mediated physiological and biochemical changes contribute to alterations in the pharmacokinetics of certain drugs. There is a paucity of data on the systematic evaluation of the underlying mechanisms. The objective of the current study was to examine the impact of changes in circulating and tissue hormonal concentration during the late stage of pregnancy on the activity and expression of hepatic cytochrome P450 (CYP) enzymes using a cocktail probe approach. METHODS: Freshly isolated primary human hepatocytes were incubated with third trimester physiologic (plasma) and projected liver (ten-fold higher) concentrations of female hormones: progesterone (2 µM), estradiol (0.3 µM), estriol (0.8 µM), estrone (0.2 µM), 17α-hydroxyprogesterone (0.1 µM), and human growth hormone (0.005 µM). The metabolic activity of the hepatocytes was assessed using a cocktail of isozyme-specific P450 probe substrates (CYP1A2 (phenacetin), CYP2C9 (diclofenac), CYP2C19 (S-mephenytoin), CYP2D6 (dextromethorphan), and CYP3A4 (testosterone)). A validated LC-MS/MS assay was used to measure the corresponding metabolite concentrations. CYP450 protein and mRNA levels were measured using western blot and qRT-PCR, respectively. RESULTS: Female hormones at projected third-semester hepatic concentrations significantly enhanced mRNA and protein expression and increased the metabolic activity of CYP3A4. The expression and activity of other CYP450 enzymes studied were not affected by mixtures of female hormones at concentrations used. CONCLUSION: The increased activity of CYP3A4 is consistent with the clinically observed increase in clearance of CYP3A4 substrates during pregnancy. Overall expression and activity of CYP450 isozymes are differentially regulated during pregnancy.

The female urethra: urethral function throughout a woman's lifetime.

INTRODUCTION AND HYPOTHESIS: The objective of this narrative review is to describe changes in urethral function that occur during a woman's lifetime. Evaluation of urethral function includes measurements of urethral closure pressure, at rest and during stress, leak point pressure, and the detailed study of anatomical and histological changes of the urethral sphincteric mechanism. METHODS: A literature search in MEDLINE, PubMed, and relevant journals from 1960 until 2020 was performed for articles dealing with urethral function and the impact of aging, pregnancy, and childbirth, female hormones, and menopausal transition on the urethral sphincteric mechanism. Longitudinal and cross-sectional epidemiological surveys, studies on histological changes in urethral anatomy during aging, and urodynamic data obtained at different points in a woman's lifetime, during pregnancy, after childbirth, as well as the effects of female hormones on urethral sphincter function are reviewed. Relevant studies presenting objective data are analyzed and briefly summarized. RESULTS AND CONCLUSIONS: The findings lead one to conclude that a constitutional or genetic predisposition, aging, and senescence are the most prominent etiological factors in the development of urinary incontinence and other pelvic floor disorders. Vaginal childbirth dilates and may damage the compressed pelvic supportive tissues and is invariably associated with a decline in urethral sphincter function. Pregnancy, hormonal alterations, menopausal transition, weight gain, and obesity are at best of secondary influence on the pathology of lower urinary tract dysfunction. The decline of circulating estrogens during menopausal transition may play a role in the transition of fibroblasts to cellular senescence.

Peripheral Neuroprotective and Immunomodulatory Effects of 5α-Reductase Inhibitors in Parkinson's Disease Models.

Gastrointestinal disorders in Parkinson's disease (PD) have been associated with neuronal alteration in the plexus of the gut. We previously demonstrated the immunomodulatory effect of female hormones to treat enteric neurodegeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. This study made the hypothesis of obtaining similar neuroprotection as with hormone treatments by affecting steroidogenesis with two 5α-reductase inhibitors, finasteride and dutasteride. These drugs are approved to treat benign prostatic hyperplasia and alopecia and display mitochondrial effects. In MPTP-treated mice, the dopaminergic and vasoactive intestinal peptide (VIP) neurons alteration was prevented by finasteride and dutasteride, while the increase in proinflammatory macrophages density was inhibited by dutasteride treatment but not finasteride. NF-κB response, oxidative stress, and nitric oxide and proinflammatory cytokines production in vitro were only prevented by dutasteride. In addition, mitochondrial production of free radicals, membrane depolarization, decreased basal respiration, and ATP production were inhibited by dutasteride, while finasteride had no effect. In conclusion, the present results indicate that dutasteride treatment prevents enteric neuronal damages in the MPTP mouse model, at least in part through anti-inflammatory and mitochondrial effects. This suggests that drug repurposing of dutasteride might be a promising avenue to treat enteric neuroinflammation in early PD.

Reproductive and hormonal risk factors for sarcoidosis: a nested case-control study.

BACKGROUND: Sarcoidosis incidence peaks in females around the fifth decade of life, which coincides with menopause, suggesting hormonal factors play a role in disease development. We investigated whether longer exposure to reproductive and hormonal factors is associated with reduced sarcoidosis risk. METHODS: We conducted a matched case-control study nested within the Mammography Screening Project. Incident sarcoidosis cases were identified via medical records and matched to controls on birth and questionnaire date (1:4). Information on hormonal factors was obtained through questionnaires prior to sarcoidosis diagnosis. Multilevel modelling was used to estimate adjusted odds ratios with 95% credible intervals (OR; 95% CI). RESULTS: In total, 32 sarcoidosis cases and 124 controls were included. Higher sarcoidosis odds were associated with older age at menarche (OR 1.19: 95% CI 0.92-1.55), natural menopause versus non-natural (OR 1.53: 95% CI 0.80-2.93), later age at first pregnancy (OR 1.11: 95% CI 0.76-1.63) and ever hormone replacement therapy (HRT) use (OR 1.40: 95% CI 0.76-2.59). Lower odds were associated with older age at menopause (OR 0.90: 95% CI 0.52-1.55), longer duration of oral contraceptive use (OR 0.70: 95% CI 0.45-1.07), longer duration of HRT use (OR 0.61: 95% CI 0.22-1.70), ever local estrogen therapy (LET) use (OR 0.83: 95% CI 0.34-2.04) and longer duration of LET use (OR 0.78: 95% CI 0.21-2.81). However, the CIs could not rule out null associations. CONCLUSION: Given the inconsistency and modest magnitude in our estimates, and that the 95% credible intervals included one, it still remains unclear whether longer estrogen exposure is associated with reduced sarcoidosis risk.

The acute effect of the menstrual cycle and oral contraceptive cycle on measures of body composition.

PURPOSE: This study aimed to investigate the effect of fluctuating female hormones during the menstrual cycle (MC) and oral contraceptive (OC) cycle on different measures of body composition. METHODS: Twenty-two women with a natural MC and thirty women currently taking combined monophasic OC were assessed over three phases of the menstrual or oral contraceptive cycle. Body weight, skinfolds, bioelectric impedance analysis (BIA), ultrasound, dual-energy X-ray absorptiometry (DXA), and peripheral quantitative computed tomography (pQCT) measurements were performed to assess body composition. Urine specific gravity (USG) was measured as an indication of hydration, and serum oestradiol and progesterone were measured to confirm cycle phases. RESULTS: Five participants with a natural MC were excluded based on the hormone analysis. For the remaining participants, no significant changes over the MC and OC cycle were found for body weight, USG, skinfolds, BIA, ultrasound and pQCT measures. However, DXA body fat percentage and fat mass were lower in the late follicular phase compared to the mid-luteal phase of the MC, while for the OC cycle, DXA body fat percentage was higher and lean mass lower in the early hormone phase compared with the late hormone phase. CONCLUSION: Our findings suggest that assessment of body fat percentage through BIA and skinfolds may be performed without considering the MC or OC cycle. Body adiposity assessment via DXA, however, may be affected by female hormone fluctuations and therefore, it may be advisable to perform repeat testing using DXA during the same phase of the MC or OC cycle.

Hysterectomy and ischemic heart disease: An observational study using propensity score methods in NHANES 2007-2018.

BACKGROUND AND AIMS: The association between hysterectomy and cardiovascular disease (CVD) remains controversial and research focusing on different types of CVD, especially ischemic heart disease, is scant. METHODS: This observational study was conducted with the National Health and Nutrition Examination Survey (NHANES) 2007-2018 using propensity score matching, propensity score overlap weighting, and logistic regression. RESULTS: Among 15,257 women, 3476 (22.78%) had hysterectomy. Compared with non-hysterectomized women, hysterectomized women are more likely to be older, obese, with lower education level, and lower annual family income. Less favorable outcomes often occurred in unadjusted analysis. In adjusted, matched, and weighted analyses, the associations between hysterectomy and all outcomes were consistent, including ischemic heart disease (ORunadjusted = 3.18[95%CI, 2.76-3.66]; ORadjusted = 1.38[95%CI, 1.09-1.73]; ORmatched = 1.37[95%CI, 1.07-1.75]; ORweighted = 1.38[95%CI, 1.12-1.71]), coronary heart disease (ORunadjusted = 3.31[95%CI, 2.71-4.05]; ORadjusted = 1.43[95%CI, 1.04-1.98]; ORmatched = 1.46[95%CI, 1.04-2.05]; ORweighted = 1.45[95%CI, 1.06-1.99]), heart attack (ORunadjusted = 3.04[95%CI, 2.51-3.68]; ORadjusted = 1.47[95%CI, 1.09-1.99]; ORmatched = 1.42[95%CI, 1.03-1.95]; ORweighted = 1.45[95%CI, 1.10-1.91]) and angina pectoris (ORunadjusted = 3.29[95%CI, 2.66-4.08]; ORadjusted = 1.34[95%CI, 0.95-1.89]; ORmatched = 1.30[95%CI, 0.91-1.87]; ORweighted = 1.33[95%CI, 0.98-1.81]). In hysterectomized women, there were no significant associations between bilateral ovariectomy and ischemic heart disease (ORunadjusted = 1.24[95%CI, 0.99-1.54]; ORadjusted = 1.05[95%CI, 0.80-1.38]; ORmatched = 1.16[95%CI, 0.86-1.55]; ORweighted = 0.93[95%CI, 0.68-1.27]), female hormones use and ischemic heart disease (ORunadjusted = 0.94[95%CI, 0.76-1.16]; ORadjusted = 0.81[95%CI, 0.62-1.07]; ORmatched = 0.89[95%CI, 0.66-1.20]; ORweighted = 1.14[95%CI, 0.88-1.49]). CONCLUSIONS: Hysterectomy may increase the risk of ischemic heart disease, especially for coronary heart disease and heart attack, but not for angina pectoris. As for the hysterectomized women, bilateral ovariectomy and female hormones use do not affect ischemic heart disease.

Potential Influence of Menstrual Status and Sex Hormones on Female Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Cross-sectional Multicenter Study in Wuhan, China.

BACKGROUND: Recent studies have indicated that females with coronavirus disease 2019 (COVID-19) have a lower morbidity, severe case rate, and mortality and better outcome than those of male individuals. However, the reasons remained to be addressed. METHODS: To find the factors that potentially protect females from COVID-19, we recruited all confirmed patients hospitalized at 3 branches of Tongji Hospital (N = 1902), and analyzed the correlation between menstrual status (n = 509, including 68 from Mobile Cabin Hospital), female hormones (n = 78), and cytokines related to immunity and inflammation (n = 263), and the severity/clinical outcomes in female patients <60 years of age. RESULTS: Nonmenopausal female patients had milder severity and better outcome compared with age-matched men (P < .01 for both). Menopausal patients had longer hospitalization times than nonmenopausal patients (hazard ratio [HR], 1.91 [95% confidence interval {CI}, 1.06-3.46]; P = .033). Both anti-Müllerian hormone (AMH) and estradiol (E2) showed a negative correlation with severity of infection (adjusted HR, 0.146 [95% CI, .026-.824], P = .029 and 0.304 [95% CI, .092-1.001], P = .05, respectively). E2 levels were negatively correlated with interleukin (IL) 2R, IL-6, IL-8, and tumor necrosis factor alpha in the luteal phase (P = .033, P = .048, P = .054, and P = .023) and C3 in the follicular phase (P = .030). CONCLUSIONS: Menopause is an independent risk factor for female COVID-19 patients. AMH and E2 are potential protective factors, negatively correlated with COVID-19 severity, among which E2 is attributed to its regulation of cytokines related to immunity and inflammation.

Influence of exogenous and endogenous estrogen on thermoregulatory responses to mild heat and the interaction with light and dark phases.

The present study aimed to determine the influence of estradiol (E2) and the interaction with circadian phases on thermoregulatory responses to mild heat in female rats. Heat loss and production during 3-h exposure to the environment at an ambient temperature of 28-34 °C were assessed by measuring abdominal temperature (Tabd), tail skin temperature, and oxygen consumption in ovariectomized rats with and without E2 replacement (OVX + E2 and OVX, respectively) and in control rats in the proestrus (P) and diestrus (D) phases. In the light phase, Tabd remained unchanged in all groups. Tabd increased in the dark phase, but was lower in the OVX + E2 and P groups than in the OVX and D groups. Oxygen consumption decreased at 34 °C, but to a lesser extent in the OVX + E2 group than in the OVX group. These results suggest that E2 activates thermoregulation in mild heat in the dark phase.

National survey of confirmed thromboembolism related to female hormones in Japan.

AIM: The aim of this study was to determine the number of thromboembolism patients among Japanese users of female hormones. METHODS: A survey of confirmed thromboembolism patients among Japanese users of female hormones was conducted at randomly selected hospitals from across Japan. The survey examined six types of venous thromboembolism (VTE) and arterial thromboembolism (ATE) in all users of female hormones, including women and men: pulmonary embolism (PE), deep vein thrombosis (DVT), other venous thrombosis (other VTE), cerebral infarction (stroke), myocardial infarction (MI) and other arterial thrombosis (other ATE). The survey covered 5 years from 2009 to 2013. This study was approved in an ethical review by the Hamamatsu University School of Medicine. RESULTS: The overall number of thromboembolism patients over the 5 years was estimated to be about 3211. They included 452 patients with PE, 795 with DVT, 157 with other VTE, 1228 with stroke, 478 with MI and 101 with other ATE. Among the abovementioned conditions, detailed information was available for 750 thromboembolism patients (645 women and 105 men), including 63 PE, 203 DVT, 159 PE + DVT, 65 other VTE, 189 stroke, 35 MI, 21 other ATE and 15 other cases. Thromboembolism increased year by year. The number of VTE was larger than that of ATE in younger people who used female hormones, while the number of ATE was larger than that of VTE in older people who used female hormones. CONCLUSION: The number and characteristics of thromboembolism patients among Japanese female hormone users were revealed in this national survey.

[Female hormones in renal physiology. Salt sensitivity and regulation of epithelial proliferation]. / Las hormonas femeninas en fisiología renal. Sensibilidad a la sal y regulación de la proliferación epitelial.

Female sex hormones participate in the regulation of blood pressure and renal epithelial proliferation, effects not related to their reproductive function. About one-third of the world's population has abnormally high levels of blood pressure, hypertension, which is responsible for almost 50% of deaths from stroke and coronary heart disease. Salt sensitivity is a risk factor for cardiovascular morbidity and mortality and other diseases as well. We reported a model of salt sensitive hypertension in adult ovariectomized (oVx) Wistar rats. oVx rats are normotensive under normal salt intake (NS, 0.24% NaCl), but upon a high salt intake (HS, 1% NaCl) oVx rats developed a blood pressure profile of salt-sensitive hypertension. Our studies on kidney molecules related to sodium balance found that the circuit dopamine D1-like receptor, cytochrome P450 4A and Na+, K+-ATPase is altered by the absence of ovary hormones which is accompanied by a reduced ability to excrete sodium. In oVx rats HS intake also promotes changes in the expression of proteins related to sodium transport in peripheral blood mononuclear cells, mainly peripheral lymphocytes. Therefore, sodium transport is modified at several levels of normal physiology. Lately, we described that estradiol increases the rate of renal epithelial cell proliferation in primary cultures developed from human renal cortex. Thus, salt sensitivity, adaptive immunity, blood pressure and renal cell proliferation are complex biological responses regulated by female sex hormones.

Un tercio de la población mundial tiene niveles anormalmente altos de presión arterial, hipertensión, responsable de casi el 50% de las muertes por accidente cerebrovascular y enfermedad coronaria. La sensibilidad a la sal es un factor de riesgo para la morbilidad y mortalidad cardiovascular y también para otras enfermedades. En estudios previos describimos un modelo de hipertensión sal sensible (HSS) en ratas Wistar ovariectomizadas (oVx) adultas. Las ratas oVx son normotensas con ingesta normal de sal (NS, 0.24% de NaCl), pero desarrollan un perfil de HSS con una ingesta elevada de sal (HS, 1% de NaCl). En los estudios en riñón encontramos que el circuito receptor D1 de dopamina, citocromo P450 4A y Na+, K+-ATPasa está alterado por la ausencia de hormonas ováricas, lo que se asocia a menor excreción de sodio e hipertensión arterial. La ingesta HS en ratas oVx también promueve cambios en la expresión de proteínas relacionadas con el transporte de sodio en células mononucleares de sangre periférica, principalmente linfocitos periféricos. Por lo tanto, el transporte de sodio se modifica en varios niveles de la fisiología normal. En estudios recientes observamos que el estradiol aumenta la proliferación y diferenciación de células epiteliales en cultivos de corteza renal humana. Sensibilidad a la sal, inmunidad adaptativa, presión arterial y proliferación de células epiteliales en riñón son fenómenos de gran importancia biológica regulados por estradiol.

Las hormonas femeninas en fisiología renal: Sensibilidad a la sal y regulación de la proliferación epitelial / Female hormones in renal physiology. Salt sensitivity and regulation of epithelial proliferation

Un tercio de la población mundial tiene niveles anormalmente altos de presión arterial, hipertensión, responsable de casi el 50% de las muertes por accidente cerebrovascular y enfermedad coronaria. La sensibilidad a la sal es un factor de riesgo para la morbilidad y mortalidad cardiovascular y también para otras enfermedades. En estudios previos describimos un modelo de hipertensión sal sensible (HSS) en ratas Wistar ovariectomizadas (oVx) adultas. Las ratas oVx son normotensas con ingesta normal de sal (NS, 0.24% de NaCl), pero desarrollan un perfil de HSS con una ingesta elevada de sal (HS, 1% de NaCl). En los estudios en riñón encontramos que el circuito receptor D1 de dopamina, citocromo P450 4A y Na+, K+-ATPasa está alterado por la ausencia de hormonas ováricas, lo que se asocia a menor excreción de sodio e hipertensión arterial. La ingesta HS en ratas oVx también promueve cambios en la expresión de proteínas relacionadas con el transporte de sodio en células mononucleares de sangre periférica, principalmente linfocitos periféricos. Por lo tanto, el transporte de sodio se modifica en varios niveles de la fisiología normal. En estudios recientes observamos que el estradiol aumenta la proliferación y diferenciación de células epiteliales en cultivos de corteza renal humana. Sensibilidad a la sal, inmunidad adaptativa, presión arterial y proliferación de células epiteliales en riñón son fenómenos de gran importancia biológica regulados por estradiol.

Female sex hormones participate in the regulation of blood pressure and renal epithelial proliferation, effects not related to their reproductive function. About one-third of the world's population has abnormally high levels of blood pressure, hypertension, which is responsible for almost 50% of deaths from stroke and coronary heart disease. Salt sensitivity is a risk factor for cardiovascular morbidity and mortality and other diseases as well. We reported a model of salt sensitive hypertension in adult ovariectomized (oVx) Wistar rats. oVx rats are normotensive under normal salt intake (NS, 0.24% NaCl), but upon a high salt intake (HS, 1% NaCl) oVx rats developed a blood pressure profile of salt-sensitive hypertension. Our studies on kidney molecules related to sodium balance found that the circuit dopamine D1-like receptor, cytochrome P450 4A and Na+, K+-ATPase is altered by the absence of ovary hormones which is accompanied by a reduced ability to excrete sodium. In oVx rats HS intake also promotes changes in the expression of proteins related to sodium transport in peripheral blood mononuclear cells, mainly peripheral lymphocytes. Therefore, sodium transport is modified at several levels of normal physiology. Lately, we described that estradiol increases the rate of renal epithelial cell proliferation in primary cultures developed from human renal cortex. Thus, salt sensitivity, adaptive immunity, blood pressure and renal cell proliferation are complex biological responses regulated by female sex hormones.

Dynamics of Vaginal and Rectal Microbiota Over Several Menstrual Cycles in Female Cynomolgus Macaques.

The composition of the microbiota in cynomolgus macaques is only partially characterized, although this animal model is often used to study pathogenesis and preventive strategies against infections. We thus performed, for the first time, a longitudinal characterization of the vaginal and rectal microbiota of five cycling female cynomolgus macaques. Samples were collected weekly for 15 weeks and the V3/V4 regions of the16S rRNA gene sequenced. Sequences were analyzed with QIIME for OTU detection and taxonomic assignment. Progesterone levels were also determined to evaluate hormonal influence on bacteria relative abundance. The rectal and vaginal bacterial composition in cynomolgus macaques is polymicrobial and clearly distinct, with larger individual variability in the vagina. Rectal microbiota profiles were consistent between animals, whereas they were highly variable and animal-specific in the vagina. In the rectum, the most abundant taxa were Ruminococcaceae, Prevotella, and Clostridiales. In the vagina, the most abundant genera were Sneathia, Porphyromonas, Prevotella, and Fusobacterium. Lactobacillus were found at relative abundances higher than 1% in only one animal and were not predominant. Comparison of the vaginal cynomolgus macaque microbiota with that of humans showed similarity to community state type IV-A usually associated with dysbiosis. In the vagina, the relative abundance of 12 bacterial genera was found to be associated with progesterone levels. Our study provides a detailed characterization of the rectal and vaginal microbiota in female cynomolgus macaques and opens new perspectives of this animal model.

Passive Stiffness of Left Ventricular Myocardial Tissue Is Reduced by Ovariectomy in a Post-menopause Mouse Model.

Background: Heart failure (HF) - a very prevalent disease with high morbidity and mortality - usually presents with diastolic dysfunction. Although post-menopause women are at increased risk of HF and diastolic dysfunction, poor attention has been paid to clinically and experimentally investigate this group of patients. Specifically, whether myocardial stiffness is affected by menopause is unknown. Aim: To investigate whether loss of female sexual hormones modifies the Young's modulus (E) of left ventricular (LV) myocardial tissue in a mouse model of menopause induced by ovariectomy (OVX). Methods: After 6 months of bilateral OVX, eight mice were sacrificed, fresh LV myocardial strips were prepared (∼8 × 1 × 1 mm), and their passive stress-stretch relationship was measured. E was computed by exponential fitting of the stress-stretch relationship. Subsequently, to assess the relative role of cellular and extracellular matrix components in determining OVX-induced changes in E, the tissues strips were decellularized and subjected to the same stretching protocol to measure E. A control group of eight sham-OVX mice was simultaneously studied. Results: E (kPa; m ± SE) in OVX mice was ∼twofold lower than in controls (11.7 ± 1.8 and 22.1 ± 4.4, respectively; p < 0.05). No significant difference between groups was found in E of the decellularized tissue (31.4 ± 12.05 and 40.9 ± 11.5, respectively; p = 0.58). Conclusion: Loss of female sexual hormones in an OVX model induces a reduction in the passive stiffness of myocardial tissue, suggesting that active relaxation should play a counterbalancing role in diastolic dysfunction in post-menopausal women with HF.

Is oestrogen associated with mandibular condylar resorption? A systematic review.

A systematic review of the literature was performed regarding the influence of oestrogen on the occurrence of mandibular condylar resorption. Search terms for oestrogen were used in combination with terms related to the effect on condylar remodelling. A search of the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases yielded 419 articles published between October 1993 and March 2017. An additional 48 articles were retrieved through manual searching of the reference lists. After initial abstract selection, 94 eligible articles were screened in detail, resulting in a final number of 33 articles included in the review. From this review, no evidence was found that oestrogen (deficiency) contributes to mandibular condylar resorption. The conclusions are limited by the lack of studies with a high level of evidence. Further investigations on serum oestrogen concentrations in women with condylar resorption are needed. Moreover, future studies should focus on the effects of the different types of medication and diseases influencing oestrogen concentrations, the utility of oestrogen concentrations during preoperative screening, and the policies for managing orthognathic surgery patients with an oestrogen deficiency. Finally, whether the mechanisms and risk factors that lead to idiopathic condylar resorption are the same in condylar resorption following orthognathic surgery remain to be elucidated.

Diurnal changes of arterial oxygen saturation and erythropoietin concentration in male and female highlanders.

In Caucasians and Native Americans living at altitude, hemoglobin mass is increased in spite of erythropoietin concentrations ([Epo]) not markedly differing from sea level values. We hypothesized that a nocturnal decrease of arterial oxygen saturation (SaO2) causes a temporary rise of [Epo] not detected by morning measurements. SaO2 (continuous, finger oximeter) and [Epo] (ELISA, every 4 h) were determined in young highlanders (altitude 2600 m) during 24 h of usual daily activity. In Series I (six male, nine female students), SaO2 fell during the night with the nadir occurring between 01:00 and 03:00; daily means (range 92.4-95.2%) were higher in females (+1.7%, P < 0.01). [Epo] showed opposite changes with zenith occurring at 04:00 without a sex difference. Mean daily values (22.9 ± 10.7SD U/L) were higher than values obtained at 08:00 (17.2 ± 9.5 U/L, P < 0.05). In Series II (seven females), only SaO2 was measured. During follicular and luteal phases, SaO2 variation was similar to Series I, but the rhythm was disturbed during menstruation. While daily [Epo] variations at sea level are not homogeneous, there is a diurnal variation at altitude following changes in SaO2 Larger hypoventilation-dependent decreases of alveolar PO2 decreases during the night probably cause a stronger reduction of SaO2 in highlanders compared to lowlanders. This variation might be enlarged by a diurnal fluctuation of Hb concentration. In spite of a lower [Hb], the higher SaO2 in women compared to men led to a similar arterial oxygen content, likely explaining the absence of differences in [Epo] between sexes.