Sleep Deprivation Triggers the Excessive Activation of Ovarian Primordial Follicles via ß2 Adrenergic Receptor Signaling.

Sleep deprivation (SD) is observed to adversely affect the reproductive health of women. However, its precise physiological mechanisms remain largely elusive. In this study, using a mouse model of SD, it is demonstrated that SD induces the depletion of ovarian primordial follicles, a phenomenon not attributed to immune-mediated attacks or sympathetic nervous system activation. Rather, the excessive secretion of stress hormones, namely norepinephrine (NE) and epinephrine (E), by overactive adrenal glands, has emerged as a key mediator. The communication pathway mediated by the KIT ligand (KITL)-KIT between granulosa cells and oocytes plays a pivotal role in primordial follicle activation. SD heightened the levels of NE/E that stimulates the activation of the KITL-KIT/PI3K and mTOR signaling cascade in an ß2 adrenergic receptor (ADRB2)-dependent manner, thereby promoting primordial follicle activation and consequent primordial follicle loss in vivo. In vitro experiments further corroborate these observations, revealing that ADRB2 upregulates KITL expression in granulosa cells via the activation of the downstream cAMP/PKA pathway. Together, these results reveal the significant involvement of ADRB2 signaling in the depletion of ovarian primordial follicles under sleep-deprived conditions. Additionally, ADRB2 antagonists are proposed for the treatment or prevention of excessive activation of primordial follicles induced by SD.

Impact of oxidative stress induced by heavy metals on ovarian function.

As a crucial organ of the female reproductive system, the ovary has both reproductive and endocrine functions. Oxidative stress refers to an increase in intracellular reactive oxygen species (ROS), which play a role in the normal physiological activity of the ovary. However, excessive ROS can cause damage to the ovary. With the advancement of human industrial activities, heavy metal pollution has become increasingly severe. Heavy metals cause oxidative stress through both direct and indirect mechanisms, leading to changes in signal transduction pathways that damage the ovaries. This review aims to outline the adverse effects of oxidative stress on the ovaries triggered by heavy metals such as copper, arsenic, cadmium, mercury, and lead. The detrimental effects of heavy metals on ovaries include follicular atresia and decreased estrogen production in experimental animals, and they also cause premature ovarian insufficiency in women. Additionally, this review discusses the role of antioxidants, provides some treatment methods, summarizes the limitations of current research, and offers perspectives for future research directions.

Identification and characterization of multipotential stem cells in immortalized normal ovarian surface epithelial cells.

The ovarian surface epithelium (OSE) is a single layer of squamous-to-cuboidal epithelial cells that experience repetitive ovulatory rupture and subsequent repair. However, the characteristics of human immortalized ovarian surface epithelial cells (IOSE80) remain elusive. This study aims to determine whether IOSE80 cells have the characteristics of stem cell proliferation and multilineage differentiation and their application in regenerative medicine. IOSE80 cells are sequenced by high-throughput transcriptome analysis, and 5 sets of public data are used to compare the differences between IOSE80 cells and bone marrow mesenchymal stem cells, pluripotent stem cells, and oocytes in transcriptome profiling. The IOSE80 cells present a cobblestone-like monolayer and express the epithelial cell marker KRT18; the stem cell markers IFITM3, ALDH1A1, and VIM; lowly express stem cell marker LGR5 and germ cell markers DDX4 and DAZL. In addition, the GO terms "regulation of stem cell proliferation", "epithelial cell proliferation", etc., are significantly enriched ( P<0.05). IOSE80 cells have the potential to act as mesenchymal stem cells to differentiate into adipocytes with lipid droplets, osteoblasts, and chondroblasts in vitro. IOSE80 cells express pluripotent stem cell markers, including OCT4, SSEA4, TRA-1-60, and TRA-1-81, and they can be induced into three germ layers in vitro. IOSE80 cells also form oocyte-like cells in vitro and in vivo. In addition, IOSE80 cells exhibit robust proliferation, migration, and ovarian repair functions after in vivo transplantation. This study demonstrates that IOSE80 cells have the characteristics of pluripotent/multipotent stem cells, indicating their important role in tissue engineering and regenerative medicine.

Effectiveness of a body shape index in predicting pediatric high blood pressure.

BACKGROUND: A body shape index (ABSI) is an emerging anthropometric indicator, challenging two traditional parameters: body mass index (BMI) and waist circumference (WC). We aimed to systematically compare and validate the capability of anthropometric indicators for determining pediatric high blood pressure (HBP). METHODS: A total of 3150 participants aged 7-17 years were enrolled from Suzhou, China. Areas under the receiver operating characteristic curve (AUC) were obtained to evaluate the performance of anthropometric indicators in detecting HBP. DeLong's test was used to examine whether the AUCs of anthropometric indicators in contrast to BMI or original ABSI were statistically different. Furthermore, a meta-analysis was performed to combine results from this study and five similar articles from databases. RESULTS: In Suzhou population, BMI exhibited the largest AUC (AUC = 0.705), followed by WC (AUC = 0.669) and original ABSI (AUC = 0.514). Modified ABSI (AUC: 0.537-0.681), although had slightly better performance than original ABSI, was still less valuable than BMI (P < 0.05), either in the total sample or in boys. The meta-analysis with 21108 children and adolescents subsequently confirms the results derived from Suzhou population. CONCLUSIONS: In predicting pediatric HBP, original ABSI and modified ABSI underperform BMI and WC. IMPACT: The current study is the first to evaluate whether original ABSI or modified ABSI is comparable to BMI and WC for screening HBP in children and adolescents. In predicting pediatric HBP, original ABSI and modified ABSI do not perform as well as traditional anthropometric indicators, such as BMI and WC. BMI remains the optimal indicator in pediatric HBP screening. This study provides a theoretical basis for the early identification of HBP in children and adolescents by adopting effective predictors.

Body Mass Index Trajectories during 6-18 Years Old and the Risk of Hypertension in Young Adult: A Longitudinal Study in Chinese Population.

BACKGROUND: Overweight/obesity in childhood is suggested to increase the risk of hypertension later in life. We aimed to assess whether and how body mass index (BMI) trajectories during 6-18 years of age are associated with hypertension in young adulthood (18-37 years) in the Chinese population. METHODS: Based on the China Health and Nutrition Survey (CHNS), a total of 1,872 participants who received ≥2 measurements of BMI during 6-18 years and had assessment of blood pressure (BP) in young adulthood were included. BMI trajectories were explored using latent class growth mixture models, and associations between identified trajectories with hypertension in young adulthood were examined by logistic regression analyses. RESULTS: Five heterogeneous BMI trajectories were identified: the low slow-increasing (20.03%), low moderate-increasing (56.14%), low rapid-increasing (17.04%), moderate-increasing (3.63%), and elevated-decreasing (3.15%) groups. Compared with the low slow-increasing group, another three increasing groups had gradually elevated risk of hypertension, yielding maximally adjusted odds ratio (95% confidence interval) (OR (95% CI)) of 2.48 (1.39-4.42), 3.24 (1.66-6.31), and 3.28 (1.19-9.08), respectively, whereas the elevated-decreasing group reversed overweight/obesity to normal weight in childhood, rendering its association with hypertension as not statistically significant (OR (95% CI) = 2.74 (0.98-7.65)). CONCLUSION: Our study indicates that there are varied BMI trajectories from childhood to adulthood and that an elevated BMI trajectory during childhood is related with an increased risk of hypertension in young adulthood. In contrast, weight loss of children with high initial BMI may mitigate or reverse the risk. Our findings emphasize the importance of BMI continuous monitoring during early life.

School-based surveillance on visit-to-visit blood pressure variability and high blood pressure in children and adolescents.

BACKGROUND: The predictive importance of visit-to-visit blood pressure variability (VVV) for high blood pressure (HBP) in a pediatric population has been largely unsettled. We aimed to evaluate it based on Health Promotion Program for Children and Adolescents (HPPCA), a school-based surveillance conducted from 2012 to 2018 in Suzhou, China. METHODS: A total of 330,618 participants had BP measurement in 2018 and ≥ 3 BP records during 2012-2017, were recruited from HPPCA. Absolute BP values (in mmHg) were converted into age-, sex- and height- normalized z-scores. VVV was expressed as standard deviation (SD), coefficient of variation (CV) or average real variability (ARV) of BP z-scores during 2012-2017. Logistic regression models were used to assess the associations between VVV and HBP in 2018. RESULTS: In 2018, 42,554 (12.87%) subjects were defined as HBP. VVV, except for SBP-CV and DBP-CV, was significantly higher in the HBP group than normotensives group. After adjusting for covariates including mean BP values from 2012 to 2017, SBP-SD, SBP-ARV, DBP-SD and DBP-ARV, increased the risk of HBP by 5.70 [95% confidence interval (95% CI) 5.54-5.87], 4.10 (95% CI 4.01-4.20), 4.70 (95% CI 4.50-4.90) and 3.39 (95% CI 3.28-3.50) times, respectively. Notably, SBP-SD significantly improved risk discrimination of HBP based on other risk variables (c-statistics, net reclassification index and integrated discrimination improvement significantly increased). CONCLUSIONS: Higher SD or ARV of BP, was independently related with higher probability of HBP in Chinese pediatric population. SBP-SD could be potentially helpful for detecting HBP. Future researches investigating the predictive value of VVV are warrant.

Gestational systolic blood pressure trajectories and risk of adverse maternal and perinatal outcomes in Chinese women.

BACKGROUND: Associations between trajectories of systolic blood pressure (SBP) during pregnancy and pregnant outcomes remain unclear and disparate. METHODS: Data of 20,353 mothers without chronic hypertension and who delivered live singletons between January, 2014 and November, 2019, was extracted from Taicang register-based cohort. Based on SBP measured during 10 to 40 weeks of gestation, SBP trajectories were explored using latent class growth mixture model, and their associations with maternal and neonatal outcomes were assessed by logistic regression analyses. RESULTS: Six heterogeneous SBP trajectories were identified: low delayed-increasing (7.47%), low reverse-increasing (21.88%), low-stable (19.13%), medium-stable (21.64%), medium reverse-increasing (16.47%), and high stable (13.41%) trajectories. The high-stable trajectory had SBP around 125 mmHg in the 10th gestational week, and increased slightly onwards. When compared with the low-stable trajectory, the high-stable trajectory had maximally adjusted odds ratio (95% confidence interval) of 5.28 (2.76-10.10), 1.30 (1.13-1.50), 1.53 (1.12-2.08), 1.32 (1.06-1.65) and 1.64 (1.08-2.48) for gestational hypertension (GH), early-term delivery (ETD), preterm delivery (PTD), small for gestational age and low birth weight (LBW), respectively. Besides, the medium reverse-increasing trajectory showed significantly increased risk of GH and ETD, while the medium-stable trajectory had significantly elevated risk of ETD and PTD. Notably, SBP trajectories slightly but significantly improved risk discrimination of GH, ETD and LBW, over traditional risk factors. CONCLUSION: Women with different SBP trajectories were at varied risk of adverse maternal and fetal outcomes. Meanwhile, our study suggested that BP monitoring during pregnancy is necessary, especially for women with high SBP in early pregnancy or upward trajectory.

Visit-to-visit blood pressure variability and risk of adverse birth outcomes in pregnancies in East China.

To investigate the potential associations between visit-to-visit blood pressure variability (VVV) and adverse birth outcomes in pregnancies, 48,209 pregnant women without proteinuria or chronic hypertension before 20 weeks of gestation who delivered live singletons between January 2014 and November 2019 in Taizhou or Taicang cities were recruited. VVV was estimated as the standard deviation and coefficient of variation of blood pressure [i.e., systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP)] measured from 20 weeks of gestation onwards. Pregnant women were classified into four groups according to the corresponding quartiles for each VVV index. It was found that VVV was significantly higher in women with small for gestational age (SGA) or low birth weight (LBW) infants than in their counterparts. Graded associations between VVV categories and poor birth outcomes were observed. In particular, when comparing the women with the highest to the lowest quartiles of standard deviation and coefficient variation of DBP, the odds ratios (95% confidence interval) for SGA was 1.15 (1.06-1.26) and 1.14 (1.05-1.25), respectively. Interestingly, the addition of DBP-VVV to established risk factors improved risk prediction of SGA; DBP-VVV demonstrated modestly superior predictive performance to VVV obtained from SBP or MAP. Similar results were found even among normotensive pregnancies. Our findings indicated that VVV during pregnancy, especially DBP-VVV, was independently associated with poor birth outcomes of pregnancies in East China. The inclusion of DBP-VVV with established risk factors may help in identifying pregnancies at high risk of SGA. Validations are needed.