Dapagliflozin prevents reproductive damage caused by acute systemic inflammation through antioxidant, anti-inflammatory, and antiapoptotic mechanisms.

Dapagliflozin (DPG) is a sodium-glucose cotransporter-2 (SGLT2) inhibitor that has been suggested to possess anti-inflammatory properties in diabetes. The aim of this study is to evaluate the role of DPG administration in preventing lipopolysaccharide (LPS)-induced damage in the female genital system. Thirty-two female Wistar Albino rats were randomly allocated into four groups: control group, LPS group, LPS + DPG group and DPG group. At the end of the experimental phase, ovary, fallopian tube and uterus tissues were collected for histopathological, immunohistochemical, genetic and biochemical analyses. The findings showed that LPS caused histopathological changes characterized by marked hyperaemia, mild to moderate haemorrhage, oedema and neutrophil leucocyte infiltrations and degenerative and necrotic changes in the female genital tract. In addition, it decreased total antioxidant status (TAS), increased total oxidant status (TOS) and oxidative stress index (OSI) levels. LPS also increased the expressions of Cas-3, G-CSF and IL-1ß in the ovary, fallopian tubes and uterus immunohistochemically. While Claudin-1 expression decreased, NLRP3 and AQP4 gene expressions increased due to LPS. However, DPG treatment prevented all these changes. The results of this study indicate that, DPG can be used to prevent LPS-induced lesions in the female reproductive system.

Association between parity and female mortality: the mediative role of depressive symptoms.

STUDY QUESTION: Is parity associated with all-cause and cause-specific mortality among women in a nationally representative cohort of the US population, and does depression mediate this association? SUMMARY ANSWER: Nulliparous women have a higher risk of all-cause and cause-specific mortality, with depression partially mediating the relationship between parity and women's all-cause and cause-specific mortality. WHAT IS KNOWN ALREADY: Parity, a significant state in reproductive life, has enduring implications for women's health. There is also a complex relationship between depression, a prevalent mental and emotional disorder, and female fertility. Previous studies have elucidated the relationships between parity and depression, both of which are associated with mortality. However, findings from studies examining parity and women's mortality have been inconsistent. Moreover, few studies have investigated whether the effect of parity on mortality is mediated by depression. STUDY DESIGN, SIZE, DURATION: We conducted a cross-sectional study using data from seven cycles of the National Health and Nutrition Examination Survey (NHANES) spanning 2005-2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study cohort comprised adult women with available parity and survival follow-up data. Parity data were self-reported and sourced from the Reproductive Health Questionnaire. Depression scores were derived from the Patient Health Questionnaire 9, and cause-specific deaths were identified using the International Statistical Classification of Diseases, 10th Revision (ICD-10). Weighted multivariable Cox regression was applied to analyze the association between parity, depression, and mortality. Weighted linear regression was performed to examine the relationship between parity and depression. Mediation analyses were employed to determine whether and to what extent depression mediated the effect of parity on mortality. MAIN RESULTS AND THE ROLE OF CHANCE: Our study ultimately encompassed 16 962 American women. Following multivariable adjustment, compared to nulliparous women, those with one to three live births exhibited a 17% and 33% reduction in all-cause and cancer mortality, respectively (all-cause mortality: HR = 0.83, 95% CI = 0.69-0.99, P = 0.040; cancer mortality: HR = 0.67, 95% CI = 0.45-0.99, P = 0.045). Women with more than four live births demonstrated lower all-cause mortality and mortality from other (not cancer or cardiovascular disease) diseases (all-cause mortality: HR = 0.73, 95% CI = 0.58-0.93, P = 0.011; other diseases mortality: HR = 0.66, 95% CI = 0.47-0.91, P = 0.013). No correlation was detected between parity and the risk of cardiovascular disease mortality among women. Furthermore, depression was found to partially mediate the impact of parity on all-cause mortality and mortality from other diseases in women. LIMITATIONS, REASONS FOR CAUTION: Firstly, a single index of parity was used as an exposure factor, and other reproductive factors such as birth spacing, age at first birth, and mode of delivery were not taken into account. Secondly, despite accounting for important potentially confounders in our analysis, such as BMI, smoking status, and educational level, the influence of unmeasured confounders (e.g., social class, latent reproductive system diseases) on reproductive behavior or mortality cannot be dismissed. Thirdly, women's vulnerability to depression fluctuates across reproductive stages, and the effect of depression on female fertility varies over time. Due to data constraints, we were unable to obtain information on women's mental health status at different reproductive stages. Fourthly, due to the data accessibility limitations of NHANES, we were unable to specifically explore the relationship between parity and different specific types of cancer, a limitation that may obscure potential correlations. Additionally, despite our efforts to control for various confounding factors in subgroup analyses, the smaller sample sizes in some subgroups may limit the statistical power, affecting the ability to detect effects. Finally, studies exploring the association between parity and depression are cross-sectional designs, making it difficult to infer causality. These results should be interpreted with caution, and further research is warranted to corroborate our findings. WIDER IMPLICATIONS OF THE FINDINGS: Our study underscores the elevated risk of all-cause and cause-specific mortality in nulliparous women and reveals that depression partially mediates the negative correlation between parity and women's all-cause mortality and mortality from other diseases. These results should be interpreted with caution, and further investigation is needed to support our findings. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Key Research and Development Program of China (2023YFC2705700), the Key Research & Developmental Program of Hubei Province (2022BCA042), and the Interdisciplinary Innovative Talents Foundation from Renmin Hospital of Wuhan University (JCRCWL-2022-001). The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Body Mass Index and Risk of Female Reproductive System Tumors Subtypes: A Meta-Analysis Using Mendelian Randomization.

Introduction: A strong association was previously established between body mass index (BMI) and female reproductive system tumors; however, the causal relationship is unclear. We conducted a Mendelian randomization (MR) study to further explore this association. Methods: Genetic information for BMI was retrieved from a published genome-wide association study involving 339,224 participants. Genetic associations with five common female reproductive system tumors were obtained from the FinnGen, UK Biobank studies, and other large consortia. Results: Genetic predisposition towards BMI exhibits a significant association with multiple tumors of the female reproductive system. Specifically, for every 1-unit increase in BMI log-transformed odds ratio (OR). The OR fluctuations overall for patients with breast cancer ranged from 0.661 to 0.996 (95% confidence interval [CI],0.544-1.000, P < 0.05). When stratified by estrogen receptor (ER) status, the OR for patients with ER (+) breast cancer ranged from 0.782 to 0.844 (95% CI, 0.616-0.994, P < 0.05) and that for those with ER (-) breast cancer ranged from 0.663 to 0.789 (95% CI, 0.498-0.991, P < 0.05). Additionally, ORs were as follows for cancer types: 1.577-1.908 (95% CI, 1.049-2.371, P < 0.05) for endometrial carcinoma; 1.216-1.303 (95% CI, 1.021-1.591, P < 0.05) for high-grade serous ovarian cancer; 1.217 (95% CI, 1.034-1.432, P < 0.05) for low-grade malignant serous ovarian cancer; and 1.502 (95% CI, 1.112-2.029, P < 0.05) for endometrioid ovarian carcinoma. Furthermore, our findings indicated that genetic predisposition towards BMI did not exhibit a causal association with uterine fibroids, cervical precancerous lesions, or cervical cancer itself. Conclusion: A genetic association was established between a high BMI and high risk of developing multiple tumors of the female reproductive system and their associated subtypes. This underscores the significance of taking measures to prevent reproductive system tumors in women who have a high BMI.

Correlation of Serum Prolactin Levels With Metabolic and Cardiovascular Risk in Greek Women With Polycystic Ovarian Syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder among females. PCOS is associated with various metabolic and cardiovascular complications, including insulin resistance, dyslipidemia, and an increased risk of type 2 diabetes mellitus and cardiovascular disease. The role of serum prolactin (PRL) in the development of these complications in PCOS is not well understood. AIM: This study aims to investigate the correlation between serum PRL levels and metabolic and cardiovascular risk factors in Greek women with PCOS. METHODS: The study utilized secondary outcomes from a prospectively collected patient database at the Third Department of Obstetrics and Gynecology, Medical School of the University of Athens. Data were collected from patients who visited the Gynecological Endocrinology - Pediatric and Adolescence Endocrinology Outpatient Clinic between January 2007 and December 2015. Measurements of various parameters, including PRL levels, BMI, waist circumference, hormone levels, lipid profiles, and insulin sensitivity, were obtained. Statistical analyses, including Mann-Whitney tests, chi-square tests, Spearman correlations, and multiple linear regression analyses, were conducted using SPSS software (IBM Corp., Armonk, NY, USA). RESULTS: The study included 247 women with PCOS, with a mean age of 24.7 years. Participants were divided into two groups based on the median PRL level. Women with higher PRL levels (>14.9) had lower BMI and waist circumference, higher levels of certain hormones and insulin sensitivity, and lower levels of fasting insulin, total cholesterol, and total lipids. Factors associated with lower PRL levels included being overweight/obese and smoking more than 10 cigarettes per day. Higher age, BMI, waist circumference, and certain hormone levels were associated with lower PRL levels. CONCLUSION: The findings suggest a correlation between serum PRL levels and metabolic and cardiovascular risk factors in Greek women with PCOS. Further research is needed to elucidate the role of PRL in the pathophysiology of PCOS and to explore its potential as a diagnostic and therapeutic target.

The marijuana, cannabinoids, and female reproductive system.

The marijuana is considered as widely used recreational illicit drug that has become popular among women of reproductive age. It is believed that the marijuana use may have negative impacts on the female fertility. However, the exact mechanisms of its reproductive toxicity remain unclear. The studies suggest that the exogenous cannabinoids may interfere with endocannabinoid system and disrupt hypothalamic-pituitary-ovary axis. Consequently, it impacts the female fertility by disruption of normal secretion of ovarian sex hormones and menstrual cycles. However, other studies have shown that medical marijuana is useful analgesic agent for pain management. But, given that the wide range of cannabinoids side effects are reported, it seems that caution should be taken in the recreational use of these substances. In summary, this article aimed to review the possible impacts of marijuana and its derivatives on the main female reproductive organs and embryonic growth and development.

Impact of dioxins on reproductive health in female mammals.

Extensive research has been conducted to investigate the toxicological impact of dioxins on mammals, revealing profound effects on the female reproductive system in both humans and animals. Dioxin exposure significantly disrupts the intricate functions of the ovary, a pivotal organ responsible for reproductive and endocrine processes. This disruption manifests as infertility, premature ovarian failure, and disturbances in sex steroid hormone levels. Comprehensive studies, encompassing accidental human exposure and experimental animal data, have raised a wealth of information with consistent yet varied conclusion influenced by experimental factors. This review begins by providing an overarching background on the ovary, emphasizing its fundamental role in reproductive health, particularly in ovarian steroidogenesis and hormone receptor regulation. Subsequently, a detailed examination of the Aryl hydrocarbon Receptor (AhR) and its role in governing ovarian function is presented. The review then outlines the sources and toxicity of dioxins, with a specific focus on AhR involvement in mediating reproductive toxicity in mammals. Within this context, the impact of dioxins, notably 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), on Folliculogenesis and Preimplantation embryos is discussed. Furthermore, the review delves into the disruptions of the female hormonal system caused by TCDD and their ramifications in endometriosis. Notably, variations in the effects of TCDD on the female reproductive and hormonal system are highlighted in relation to TCDD dose, animal species, and age. As a forward-looking perspective, questions arise regarding the potential involvement of molecular mechanisms beyond AhR in mediating the female reproductive toxicity of dioxins.

Therapeutic effects of saffron (Crocus sativus L) on female reproductive system disorders: A systematic review.

The effect of Crocus sativus on several disorders has been discussed or even confirmed, but the efficacy of this herb on the female reproductive system has not been well presented. In this regard, this systematic review comprehensively discussed the efficacy of C. sativus and its main phytochemical compounds on the female reproductive system and its disorders for the first time. In this systematic review, scientific databases, including PubMed, Web of Sciences, Google Scholar, Scopus, and Scientific Information Database, were explored profoundly. In vivo, in vitro, and human studies published until the end of July 2023, which had investigated the pharmacological properties of C. sativus, crocin, crocetin, safranal, or picrocrocin on the female reproductive system, were selected. A total of 50 studies conducted on the effect of C. sativus on the female reproductive system were acquired. These studies confirmed the efficacy of C. sativus or its main phytochemical ingredients in several aspects of the female reproductive system, including regulation of sex hormones, folliculogenesis, ovulation, and protection of the ovary and uterus against several oxidative stress. Several retrieved studies indicated that this herb also can alleviate the symptoms of patients suffering from dysmenorrhea, premenstrual syndrome, menopause, polycystic ovary disease (PCOD), and sexual dysfunction. Furthermore, it is a promising candidate for future studies or even trials regarding ovarian and cervical cancers. This review concluded that C. sativus can improve the symptoms of several female reproductive system disorders, which is particularly due to the presence of phytochemical ingredients, such as crocin, crocetin, and safranal.

Mechanisms of female reproductive toxicity in pigs induced by exposure to environmental pollutants.

Environmental pollutants, including endocrine disruptors, heavy metals, nanomaterials, and pesticides, have been detected in various ecosystems and are of growing global concern. The potential for toxicity to non-target organisms has consistently been raised and is being studied using various animal models. In this review, we focus on pesticides frequently detected in the environment and investigate their potential exposure to livestock. Owing to the reproductive similarities between humans and pigs, various in vitro porcine models, such as porcine oocytes, trophectoderm cells, and luminal epithelial cells, are used to verify reproductive toxicity. These cell lines are being used to study the toxic mechanisms induced by various environmental toxicants, including organophosphate insecticides, pyrethroid insecticides, dinitroaniline herbicides, and diphenyl ether herbicides, which persist in the environment and threaten livestock health. Collectively, these results indicate that these pesticides can induce female reproductive toxicity in pigs and suggest the possibility of adverse effects on other livestock species. These results also indicate possible reproductive toxicity in humans, which requires further investigation.

Low doses of malathion impair ovarian, uterine, and follicular integrity by altering oxidative profile and gene expression of rats exposed during the peripubertal period.

Malathion serves as a pivotal pesticide in agriculture and the management of the Aedes aegypti mosquito. Despite its widespread use, there is a notable absence of studies elucidating the mechanisms through which malathion may affect the female reproductive system. Consequently, the objective of this investigation was to assess whether exposing juvenile female rats to low doses of malathion during the juvenile and peripubertal periods could compromise pubertal onset, estradiol levels, and the integrity of the ovaries and uterus while also examining the underlying mechanisms of damage. To achieve this, thirty juvenile female rats were subjected to either a vehicle or malathion (10 mg/kg or 50 mg/kg) between postnatal days 22 and 60, with subsequent verification of pubertal onset. Upon completion of the exposure period, blood samples were collected for estradiol assessment. The ovaries and uterus were then examined to evaluate histological integrity, oxidative stress, and the expression of genes associated with cell proliferation, antiapoptotic responses, and endocrine pathways. Although estradiol levels and pubertal onset remained unaffected, exposure to malathion compromised the integrity and morphometry of the ovaries and uterus. This was evidenced by altered oxidative profiles and changes in the expression of genes regulating the cell cycle, anti-apoptotic processes, and endocrine pathways. Our findings underscore the role of malathion in inducing cell proliferation, promoting cell survival, and causing oxidative damage to the female reproductive system in rats exposed during peripubertal periods.

The utilization of nanotechnology in the female reproductive system and related disorders.

The health of the reproductive system is intricately linked to female fertility and quality of life. There has been a growing prevalence of reproductive system disorders among women, particularly in younger age groups, resulting in significant adverse effects on their reproductive health. Consequently, there is an urgent need for effective treatment modalities. Nanotechnology, as an advanced discipline, provides innovative avenues for managing and treating diseases of the female reproductive system by enabling precise manipulation and regulation of biological molecules and cells. By utilizing nanodelivery systems, drugs can be administered with pinpoint accuracy, leading to reduced side effects and improved therapeutic efficacy. Moreover, nanomaterial imaging techniques enhance diagnostic precision and sensitivity, aiding in the assessment of disease severity and progression. Furthermore, the implementation of nanobiosensors facilitates early detection and prevention of ailments. This comprehensive review aims to summarize recent applications of nanotechnology in the treatment of female reproductive system diseases. The latest advancements in drug delivery, diagnosis, and treatment approaches will be discussed, with an emphasis on the potential of nanotechnology to improve treatment outcomes and overall quality of life.

Prolonged testosterone 17ß-cyclopentylpropionate exposition induces behavioral, ovarian, oviductal, uterine and reproductive disturbances in female mice.

Anabolic-androgenic steroids (AAS) abuse is often associated with metabolic disorders and infertility. However, the current evidence on AAS-induced reproductive toxicity is mainly based on male studies. Thus, AAS repercussions on female reproductive capacity remain poorly understood, despite scarce evidence that fertility determinants may be more severely impaired in females than males exposed to these drugs. Accordingly, this study used an integrated framework to investigate the impact of different testosterone 17ß-cyclopentylpropionate (TC) doses on pain sensitivity, aggressiveness, anxiety, sexual behavior, ovarian, oviductal, uterine and reproductive morphofunctional and molecular outcomes. These parameters were used to explore the reproductive capacity in female mice exposed to this synthetic testosterone ester. The animals were untreated or intraperitoneally treated with 5, 10 and 20 mg/kg TC every 48 h for 12 weeks. Our findings indicated that testosterone was upregulated while the hormones luteinizing, follicle-stimulating, estrogen and progesterone were down-regulated by TC. This AAS also exerted deleterious effects on anxiety, aggressivity, nociception, exploratory and sexual behavior in female mice. Concurrently, TC attenuated ovarian follicle maturation, interrupted the estrous cycle, induced oviductal and uterine hypotrophy. Estrous cyclicity was reestablished 60 days after AAS treatment. However, TC-treated mice still exhibited impaired reproductive capacity, a disturbance potentially related to deficiency in folliculogenesis, sex hormones production, and endometrial receptivity mediate by ER-α, PR, HOXA-10 and LIF down-regulation. Taken together, our findings indicated that in addition to female behavior, reproductive organs microstructure and function are markedly impaired by TC in a dose-dependent manner, whose time-dependent reversibility remains to be clarified.

Therapeutic effects of garlic (Allium sativum) on female reproductive system: A systematic review.

Complementary and alternative medicine, including Persian medicine (PM), offers a variety of disease prevention and treatment methods, including the application of medicinal plants. The health of the reproductive system is an important issue for women, and understanding the potential effect of garlic (Allium sativum) for preventive and therapeutic purposes in this field is of interest. This systematic review focused on the effects of garlic on the female reproductive system. The method involved a comprehensive search of relevant literature on experimental animal studies using electronic databases from January 2010 to September 2023, followed by selection of eligible studies and data extraction. A total of 18 studies met the inclusion criteria and were included in the review. This review reported that garlic may have positive effects on women's reproductive health, such as improving hormonal balance, relieving PMS symptoms, and potentially supporting fertility outcomes. This review revealed that garlic compounds such as allicin and ajoene can modulate various aspects of the female reproductive system, including regulation of the menstrual cycle, hormonal balance, fertility, and reproductive disorders. This review determined that further research is needed to elucidate the molecular pathways and direct effects of garlic on the female reproductive system. Although garlic has many potential health benefits, it should not be used as a substitute for medications.

Prognostic value of insulin resistance in patients with female reproductive system malignancies: A multicenter cohort study.

BACKGROUND: Insulin resistance (IR) and systemic inflammation are common in patients with cancer and are associated with poor prognosis. Few studies have reported IR in female reproductive system malignancies. This study investigated the prognostic value of IR and systemic inflammation in this population. METHODS: A prospective multicenter real-world cohort study involving 571 patients diagnosed with female reproductive system malignancies was conducted. Lipid ratios (low-density lipoprotein-cholesterol/high-density lipoprotein-cholesterol [LHR], total cholesterol/HDL-cholesterol [TCHR], triglyceride/HDL-cholesterol [TGHR], fasting triglyceride/glucose [TyG]) were used to reflect IR. Optimal cut-off values were determined using maximally selected rank statistics. The Kaplan-Meier and Cox regression were used to calculate the hazard ratios for overall survival. RESULTS: Over half (55.90%) of the 571 patients with female reproductive system malignancies (mean age: 52 years) had cervical cancer. Both IR and inflammation were negatively correlated with overall survival in female reproductive system cancer patients. Multivariate survival analysis showed that patients with high LHR (hazard ratio [HR]: 1.51, 95% confidence interval [CI]: 1.01-2.25, p = .046), high TCHR (HR: 1.90, 95% CI:1.22-2.95, p = .005), high TGHR (HR: 1.66, 95% CI:1.17-2.36, p = .004), high TyG (HR: 1.64, 95% CI:1.13-2.40, p = .010), high neutrophil lymphocyte ratio (NLR, HR: 2.03, 95% CI:1.44-2.86, p = .004) were significantly associated with worse prognosis. By calculating the concordance index of the four IR surrogate indicators, TyG was the most valuable indicator for the prognosis of patients with malignant tumors of the female reproductive system. High TyG combined with high NLR had improved prognostic value (HR: 3.22, 95% CI: 1.97-5.26, p < .001). CONCLUSIONS: IR can be used as an independent predictor of prognosis in the female reproductive system malignancy population regardless of the IR substitution index. The combination of TyG and NLR could better predict the prognostic outcomes of women with breast cancer.

Effect of COVID-19 on Menstruation and Lower Reproductive Tract Health.

Background: To evaluate the dynamically impact of the coronavirus disease 2019 (COVID-19) on the female reproductive system. Methods: An online survey was shared to women of reproductive age who had been infected with COVID-19 and recovered in China between January and March 2023. Results: In total, 610 women of childbearing age completed the menstrual component of the survey and 82.6% (n=504) women self-purchased medications without hospitalization. 254 women were menstruating during COVID-19 infection. 66.9% of them reported changes in menstruation, including cycle length (64.7%), menstrual flow (72.4%), and duration (53%), compared to pre-COVID-19. COVID-19-related chest tightness (OR: 9.5; 95% CI: 1.9-46.3), COVID-19-related stress (OR: 18.4; 95% CI: 1.4-249.7), and COVID-19-related low mood (OR: 6.2; 95% CI: 1.4-28.2) were associated with these menstrual changes. However, over 73% of women who menstruated during and after COVID-19 regained their pre-infection menstrual cycle (73%), duration (79.6%), and flow (75.2%) during their first menstruation after COVID-19 recovery. Compared to pre-infection, 19.7% (n=124) women reported changes in lower reproductive tract during COVID-19, including volume and color of vaginal discharge, vulvar pruritus, and vaginitis. These changes were significantly increased in those with a history of pelvic inflammatory disease (OR: 12.1; 95% CI: 3.1-48.2), ovarian cysts (OR: 4.9; 95% CI: 1.2-19.4), and vaginitis (OR: 5.5; 95% CI: 2.1-14.4) prior to COVID-19. However, 52.4% reported that their lower reproductive tract health had returned to its pre-infection within the first month after recovery from COVID-19, while 73.5% reported a return to the pre-infection within 2 months. Conclusion: Changes in menstruation and lower reproductive tract associated with COVID-19 are transient. Menstruation and lower reproductive tract health will gradually return to pre-COVID-19 status within 2 months of recovery, which can help alleviate excessive concerns about the effects of COVID-19 on the reproductive system.

Revolutionizing the female reproductive system research using microfluidic chip platform.

Comprehensively understanding the female reproductive system is crucial for safeguarding fertility and preventing diseases concerning women's health. With the capacity to simulate the intricate physio- and patho-conditions, and provide diagnostic platforms, microfluidic chips have fundamentally transformed the knowledge and management of female reproductive health, which will ultimately promote the development of more effective assisted reproductive technologies, treatments, and drug screening approaches. This review elucidates diverse microfluidic systems in mimicking the ovary, fallopian tube, uterus, placenta and cervix, and we delve into the culture of follicles and oocytes, gametes' manipulation, cryopreservation, and permeability especially. We investigate the role of microfluidics in endometriosis and hysteromyoma, and explore their applications in ovarian cancer, endometrial cancer and cervical cancer. At last, the current status of assisted reproductive technology and integrated microfluidic devices are introduced briefly. Through delineating the multifarious advantages and challenges of the microfluidic technology, we chart a definitive course for future research in the woman health field. As the microfluidic technology continues to evolve and advance, it holds great promise for revolutionizing the diagnosis and treatment of female reproductive health issues, thus propelling us into a future where we can ultimately optimize the overall wellbeing and health of women everywhere.

Destination integration: linking physiology, histology, and embryology content in foundational sciences.

Anatomy and physiology are tightly linked disciplines that complement each other, however, in medical education delivery of this content is often siloed and divided. To address this, we created combined anatomy and physiology content for the female reproductive system, and team-taught designated histology and embryology topics integrated with the physiology content. Collectively, this created a more holistic incorporation of topics for student learning. Here we describe the format and approach for this teaching innovation.

Icariin, A Novel Promising Complementary Therapeutic Strategy in the Management of Female Infertility: A Literature Review:.

The prevalence of pre-menopausal female infertility is increasing considerably due to various causes such as environmental pollutants, increased administration of chemotherapeutics and radiation exposure, microbial infections, and genetic/epigenetic alterations. However, the current therapeutical strategies remain unfavorite as the disadvantages are strongly challenging. Icariin (ICI) is a phytoestrogen that exerts some promising properties in order to alleviate female infertility. Therefore, the current literature review aimed to evaluate the conducted studies regarding the beneficial impacts of ICI on the female reproductive system and female fecundity. The findings of the present study revealed that ICI is able to modulate the levels of reproductive hormones as it causes a significant decrement in the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) while increasing the levels of estrogen and progesterone. Furthermore, the administration of ICI results in a dramatic alteration in the expression of sex steroids’ receptors, particularly in female reproductive tissues. In addition, preserving ovarian follicular reserve, improving the ovarian and uterine histoarchitecture, elongating the estrous cycle duration, and eventually advancing the female fecundity are other major effects of ICI on the female reproductive system. Despite these desired beneficial properties, the current knowledge appears to be insufficient, hence further investigations, particularly on humans, are encouraged. To the best of our knowledge, this review provides a comprehensive information regarding the beneficial effects of Icariin on female infertility for the firs time.

Predicting chemicals' toxicity pathway of female reproductive disorders using AOP7 and deep neural networks.

Experimental evidence shows that certain chemicals, particularly endocrine disrupting chemicals, may negatively affect the female reproductive system, thereby lowering women's fertility. However, humans are constantly exposed to a number of different chemicals with limited or no experimental data regarding their effect and the mechanism of action in the female reproductive system. To predict chemical hazards to the female reproductive system, we used a previously defined adverse outcome pathway (AOP) that links activation of the peroxisome proliferator-activated receptor γ to the reproductive toxicity in adult females (AOP7) and the Convolutional Deep Neural Network models that produce meaningful predictions when trained on a significant amount of data. The models trained using CompTox assays with intended molecular and biological targets corresponding to AOP7 achieved high performance (over 90% validation accuracy). The integration of AOP7 and Deep Neural Network identified chemicals that could negatively affect female reproduction through the mechanism described in AOP7. We provide a solution to quickly analyze the data and produce machine learning models to identify potentially active chemicals in the female reproductive system. Although we focused on the female reproductive system, this approach could be valid for a number of other chemicals and AOPs if the right data exist.

Immunohistochemical and ultrastructural identification of telocytes in the lamina propria of human vaginal mucosa.

Since their relatively recent discovery, telocytes (TCs) have been described as peculiar cells strategically positioned in the stromal tissue component of multiple organ systems of the mammalian body including female reproductive organs (i.e., ovary, uterine tube, and uterus). Nevertheless, current knowledge of TCs in the vagina is very limited. The present study was therefore undertaken to investigate the existence and characteristics of TCs in the stromal tissue of human vaginal mucosa by means of immunohistochemistry, immunofluorescence confocal microscopy, and transmission electron microscopy. In the vaginal lamina propria, TCs were first identified by CD34 immunohistochemistry that revealed the presence of CD34+ stromal cells arranged in networks, especially around blood vessels. Double immunofluorescence confocal microscopy allowed to precisely distinguish the perivascular networks of CD34+ stromal cells lacking CD31 immunoreactivity from adjacent CD31+ microvessels. All the perivascular networks of TCs/CD34+ stromal cells situated in the vaginal lamina propria coexpressed platelet-derived growth factor receptor α, which strengthened their identification as TCs. Instead, vaginal mucosal TCs were immunophenotypically negative for c-kit/CD117. The ultrastructural examination confirmed the presence of TCs, namely stromal cells with characteristic cytoplasmic processes (i.e., telopodes) forming labyrinthine networks around blood vessels and releasing extracellular vesicles. Together, our morphological findings provide the first comprehensive demonstration that TCs reside in the human vaginal lamina propria, thus paving the way for further investigation of their putative functions in vaginal mucosal homeostasis and pathophysiology.