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Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder affecting 6-20% of women of childbearing age worldwide. Immune cell imbalance and dysregulation of inflammatory factors can lead to systematic low-grade chronic inflammation (SLCI), which plays a pivotal role in the pathogenesis of PCOS. A significant higher infiltration of immune cells such as macrophages and lymphocytes and pro-inflammatory factors IL-6 and TNF-α has been detected in PCOS organ systems, impacting not only the female reproductive system but also other organs such as the cardiovascular, intestine, liver, thyroid, brain and other organs. Obesity, insulin resistance (IR), steroid hormones imbalance and intestinal microecological imbalance, deficiencies in vitamin D and selenium, as well as hyperhomocysteinemia (HHcy) can induce systematic imbalance between pro-inflammatory and anti-inflammatory cells and molecules. The pro-inflammatory cells and cytokines also interact with obesity, steroid hormones imbalance and IR, leading to increased metabolic imbalance and reproductive-endocrine dysfunction in PCOS patients. This review aims to summarize the dysregulation of immune response in PCOS organ system and the intrinsic mechanisms affecting SLCI in PCOS to provide new insights for the systemic inflammatory treatment of PCOS in the future.

The essential cause of menopause is ovarian failure, which can cause decline in sex hormones (especially estrogen) that can increase the risk of metabolic diseases, such as cardiovascular disease and osteoporosis. This study screened 1511 eligible patients from 2148 perimenopausal and postmenopausal women, measuring various physiological and biochemical indicators to analyze differences among age groups (40–44, 45–49, and 50–54 years) with laboratory techniques. The study found no significant difference in the incidence of cardiovascular disease betweenperimenopausal and postmenopausal women. But the incidence of osteoporosis was higher in postmenopausal women and was associated with age ( p  < 0.05). Additionally, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E 2 ), total cholesterol (TC), lumbar spine bone mineral density (BMD) (T1), right femoral BMD (T2) and femoral neck BMD were significantly correlated in both groups. Significant differences were observed in FSH, LH, E 2 , TC, low-density lipoprotein (LDL), L2-L4, T 1 , femoral neck reduction and T 2 among women in different age groups. Correlation analysis indicated that age increased the risk of cardiovascular disease and osteoporosis in bothperimenopausal and postmenopausal women. This study contributes to a deeper understanding of the pathogenesis of cardiovascular disease and osteoporosis in perimenopausal and menopausal women.

Physical exercise is able to improve skeletal health. However, the mechanisms are poorly known. Irisin, a novel exercise-induced myokine, secreted by skeletal muscle in response to exercise, have been shown to mediate beneficial effects of exercise in many disorders. In the current study, we demonstrated that irisin promotes osteoblast proliferation and increases the expression of osteoblastic transcription regulators, such as Runt-related transcription factor-2, osterix/sp7; and osteoblast differentiation markers, including alkaline phosphatase, collagen type 1 alpha-1, osteocalcin and osteopontin in vitro . Irisin also increase ALP activity and calcium deposition in cultured osteoblast. These osteogenic effects were mediated by activating the p38 mitogen-activated protein kinase (p-p38 MAPK) and extracellular signal-regulated kinase (ERK). Inhibition of p38 MAPK by SB203580 or pERK by U0126 abolished the proliferation and up-regulatory effects of irisin on Runx 2 expression and ALP activity. Together our observation suggest that irisin directly targets osteoblast, promoting osteoblast proliferation and differentiation via activating P38/ERK MAP kinase signaling cascades in vitro . Whether irisin can be utilized as the therapeutic agents for osteopenia and osteoporosis is worth to be further pursued

Irisin is a product of fibronectin type III domain-containing protein ( Fndc5 ) and is involved in the regulation of adipokine secretion and the differentiation of osteoblasts and osteoclasts. In this study, we aimed to determine whether irisin lacking affects glucose/lipid and bone metabolism. We knocked out the Fndc5 gene to generate irisin-lacking mice. Remarkable, irisin lacking was related to poor ‘browning response’, with a bigger size of the intraperitoneal white adipose cell and decreased a number of brown adipose cells in brown adipose of interscapular tissue. The irisin lacking mice had hyperlipidemia and insulin resistance, reduced HDL-cholesterol level, increased LDL-cholesterol level, and decreased insulin sensitivity. The lacking of irisin was associated with reduced bone strength and bone mass in mice. The increased number of osteoclasts and higher expression of RANKL indicated increased bone resorption in irisin lacking mice. The level of IL-6 and TNF-α also increased in irisin lacking mice. The results showed that irisin lacking was related to decreased ‘browning response’, glucose/lipid metabolic derangement, and reduced bone mass with increased bone resorption. Further studies are needed to confirm these initial observations and explore the mechanisms underlying the effects of irisin on glucose/lipid and bone metabolism.

Background Irisin, which is cleaved from fibronectin type III domain-containing protein 5 ( Fndc5 ), plays an important role in energy homeostasis. The link between energy metabolism and reproduction is well known. However, the biological actions of irisin in reproduction remain largely unexplored. Methods In this study, we generated Fndc5 gene mutation to create irisin deficient mice. Female wild-type (WT) and Fndc5 mutant mice were fed with standard chow for 48 weeks. Firstly, the survival rate, body weight and fertility were described in mice. Secondly, the levels of steroid hormones in serum were measured by ELISA, and the estrus cycle and the appearance of follicles were determined by vaginal smears and ovarian continuous sections. Thirdly, mRNA-sequencing analysis was used to compare gene expression between the ovaries of Fndc5 mutant mice and those of WT mice. Finally, the effects of exogenous irisin on steroid hormone production was investigated in KGN cells. Results The mice lacking irisin presented increased mortality, reduced body weight and poor fertility. Analysis of sex hormones showed decreased levels of estradiol, follicle-stimulating hormone and luteinizing hormone, and elevated progesterone levels in Fndc5 mutant mice. Irisin deficiency in mice was associated with irregular estrus, reduced ratio of antral follicles. The expressions of Akr1c18 , Mamld1 , and Cyp19a1 , which are involved in the synthesis of steroid hormones, were reduced in the ovaries of mutant mice. Exogenous irisin could promote the expression of Akr1c18 , Mamld1 , and Cyp19a1 in KGN cells, stimulating estradiol production and inhibiting progesterone secretion. Conclusions Irisin deficiency was related to disordered endocrinology metabolism in mice. The irisin deficient mice showed poor growth and development, and decreased fertility. Irisin likely have effects on the expressions of Akr1c18 , Mamld1 and Cyp19a1 in ovary, regulating the steroid hormone production. This study provides novel insights into the potential role of irisin in mammalian growth and reproduction.

Background The optimal management of patients in reproductive endocrinology relies on the accuracy and validity of sex hormone assays. Endogenous or exogenous substances can compete with the analyte. This competition can result in interfering errors and falsely indicate elevated serum levels. Obvious interference in estradiol assays appears to occur rarely. Consequently, clinicians who are not familiar with the potential of interference could be misled. In addition to unnecessary investigations and interventions and severe mental stress, falsely elevated estradiol results can result in missed or delayed fertility opportunities. Case A 28-year-old female with pregnancy demand was diagnosed with polycystic ovary syndrome, Hashimoto’s thyroiditis and subclinical hypothyroidism. She was found to have persistently elevated levels of serum estradiol in the early follicular phase (between 527 and 642 pg/mL). Screening workup was performed for nearly 11 months to find the causes. Serum tumor biomarkers were normal. Abdominal and pelvic computed tomography were negative for adrenal or adnexal masses. A left mesosalpinx cyst and benign pathological results were achieved by laparoscopic surgery. Hormonal substances and dietary supplements were absent, as determined by dietary records. Ultrasound confirmed follicles could grow slowly and eventually ovulate. Falsely elevated estradiol levels were suspected due to the discrepancy among high estradiol levels, follicle growth and normal gonadotropin levels. Immunological interference by heterophile antibody was finally verified by two competitive chemiluminescent immunoassay platforms (estradiol levels in the early follicle phase: 619 pg/mL, Siemens ADVIA CENTAUR and 60 pg/mL, Beckman, DxI 800). Successful clinical pregnancy was eventually achieved by combining induced ovulation, ultrasound monitoring and intercourse guidance. Conclusions Analytical interference and laboratory error should be suspicious at first when the clinical characteristics contradict the laboratory results of serum hormones. Measuring serum estradiol with another immunoassay platform is an easy and non-time-consuming method to exclude the heterophile interfering.

Single cell approaches have increased our knowledge about the cell type composition of the non-human primate (NHP), but a detailed characterization of area-specific regulatory features remains outstanding. We generated single-cell transcriptomic and chromatin accessibility (single-cell ATAC) data of 358,237 cells from prefrontal cortex (PFC), primary motor cortex (M1) and primary visual cortex (V1) of adult female cynomolgus monkey brain, and integrated this dataset with Stereo-seq (spatial enhanced resolution omics-sequencing) of the corresponding cortical areas to assign topographic information to molecular states. We identified area-specific chromatin accessible sites and their targeted genes, including the cell type-specific transcriptional regulatory network associated with excitatory neurons heterogeneity. We reveal calcium ion transport and axon guidance genes related to specialized functions of PFC and M1, identified the similarities and differences between adult macaque and human oligodendrocyte trajectories, and mapped the genetic variants and gene perturbations of human diseases to NHP cortical cells. This resource establishes a transcriptomic and chromatin accessibility combinatory regulatory landscape at a single-cell and spatially resolved resolution in NHP cortex. Cell type epigenetic and topographic information of primate brain is lacking. Here, authors identified transcriptional regulatory network, gradient expression pattern and disease vulnerability at cell type level in PFC, M1 and V1 of monkey brain by snRNAseq, snATAC-seq and Stereo-seq.

Background Antenatal depression (AD) is considered as one of the major health burdens and has adverse effects on the outcome of expectant mothers and newborns. The present study aims to investigate the prevalence of antenatal depression (AD), and to explore the potential risk factors of AD among pregnant women in Chengdu, including personal background, related social factors, family factors and cognitive factors. Methods The prospective nested case-control study included pregnant women who were in their second pregnancy and attended prenatal care at three tertiary hospitals and one regional hospital in Chengdu, China, between March 2015 and May 2016. Self-designed questionnaires were given to participants in their second and third trimesters to collect information on clinical and demographic characteristics, and a modified edition of Edinburgh Postnatal Depression Scale (EPDS) were used to measure AD. The logistic regression was applicated in analyses. Results A total of 996 pregnant women were included in analysis. Ninety-three women suffered from AD symptoms only in their second trimester, 96 only in their third trimester, and 107 displayed persistent depression in both trimesters. In the univariate analyses, age and marital relationships were linked with AD occurrence in both second and third trimester. In addition, increasing age, full-time job, higher education level, and no gender preference of spouse were associated with reduced persistent depression. Multivariate analysis showed that gender preference and marital relationship were the potential risk factors of persistent depression. Conclusions Age, marital relationship relationships, with parents-in-law, the negative recognition of this pregnancy and husband’s gender preference were found as risk factors of AD occurrence in some specific trimester. Gender preference of husbands and marital relationships were independently associated with persistent depression. These findings suggest that stronger family support can help improve mental health of pregnant women.