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Abnormal body mass index (BMI) has been associated with pregnancy complications and adverse pregnancy outcomes; however, its clinical significance during early pregnancy remains unclear. This study aimed to investigate the relationships and underlying mechanisms between maternal BMI, reproductive endocrine parameters, and pregnancy outcomes, thereby providing a theoretical basis and clinical guidance for the management of pregnancies in women with abnormal BMI. A total of 353 pregnant women were enrolled in this study and categorized into four groups according to BMI: underweight (n = 45), normal weight (n = 229), overweight (n = 57), and obese (n = 22). At 6-8 weeks of gestation, pregnancy-related hormones, glucose and lipid metabolism parameters, and uterine artery blood flow indices were collected and analyzed. Pregnancy outcomes and neonatal birth information were also recorded. In addition, an obese mouse model was established to evaluate maternal weight changes during pregnancy and their effects on uterine and embryonic development. The expression of genes and proteins related to en[docrine metabolism, inflammatory regulation, and angiogenesis was assessed using RT-qPCR and Western blot techniques to further explore the potential mechanisms involved. During early pregnancy, pregnant women with low BMI exhibited significantly lower estradiol levels (P < 0.05). In contrast, women with high BMI had significantly reduced levels of human chorionic gonadotropin, estradiol, and progesterone, along with markedly elevated glucose and lipid metabolism parameters (P < 0.05). However, BMI had no significant impact on uterine artery blood flow indices, live birth rate, gestational age, or mode of delivery (P > 0.05). High BMI was associated with an increased risk of macrosomia in neonates (P < 0.05). In the animal experiments, obese pregnant mice exhibited significantly greater gestational weight gain compared to controls (P < 0.05), and their offspring showed a predisposition to obesity. RT-qPCR analysis revealed that, relative to the control group, mRNA expression levels of VEGFA, VEGFR-2, CD31, and SIRT1 were significantly decreased in the obese group (P < 0.001), whereas mRNA expression of GLUT1, HIF-1α, TNF-α, IL-6, HMGB1, and TLR4 was significantly upregulated (P < 0.01). Western blot results demonstrated that compared with controls, the obese group showed significantly lower expression levels of GLUT4 and phosphorylated IRS1 (P < 0.0001), while the expression of HIF-1α and TNF-α was significantly increased (P < 0.0001). Additionally, there were no significant differences in the protein expression levels of IRS1, SGK1, and NFκB p65 between the two groups (P > 0.05). Abnormal BMI affects hormonal profiles and glucose and lipid metabolism during early pregnancy. Although it does not significantly impact fetal survival rates, it markedly increases the risks of cesarean delivery, preterm birth, and abnormal neonatal birth weight. These alterations not only pose challenges for postpartum maternal and neonatal health management but may also exert adverse effects on the long-term health of the offspring. Maternal obesity may impair pregnancy outcomes by inhibiting insulin signaling, enhancing proinflammatory responses, inducing a hypoxic microenvironment in the decidual tissue, and suppressing angiogenesis, thereby disrupting maternal-fetal interface homeostasis.

Background Decidual macrophages participate in immune regulation at the maternal–fetal interface. Abnormal M1/M2 polarization of decidual macrophages might predispose immune maladaptation in recurrent pregnancy loss (RPL). However, the mechanism of decidual macrophage polarization is unclear. We explored the role of Estradiol (E 2 )-sensitive serum-glucocorticoid regulated kinase (SGK) 1 in promoting macrophage polarization and suppressing inflammation at the maternal–fetal interface. Methods We assessed serum levels of E 2 and progesterone during first trimester of pregnancy in women with or without threatened miscarriages (ended in live birth, n  = 448; or early miscarriages, n  = 68). For detection of SGK1 in decidual macrophages, we performed immunofluorescence labeling and western blot analysis applying decidual samples from RPL ( n  = 93) and early normal pregnancy ( n  = 66). Human monocytic THP-1 cells were differentiated into macrophages and treated with Toll-like receptor (TLR) 4 ligand lipopolysaccharide (LPS), E 2 , inhibitors or siRNA for in vitro analysis. Flow cytometry analysis were conducted to detect macrophages polarization. We also applied ovariectomized (OVX) mice with hormones exploring the mechanisms underlying the regulation of SGK1 activation by E 2 in the decidual macrophages in vivo. Results SGK1 expression down regulation in the decidual macrophages of RPL was consistent with the lower concentration and slower increment of serum E 2 from 4 to 12 weeks of gestation seen in these compromised pregnancies. LPS reduced SGK1 activities, but induced the pro-inflammatory M1 phenotype of THP-1 monocyte-derived macrophages and T helper (Th) 1 cytokines that favored pregnancy loss. E 2 pretreatment promoted SGK1 activation in the decidual macrophages of OVX mice in vivo. E 2 pretreatment amplified SGK1 activation in TLR4-stimulated THP-1 macrophages in vitro through the estrogen receptor beta (ERβ) and PI3K pathway. E 2 -sensitive activation of SGK1 increased M2 macrophages and Th2 immune responses, which were beneficial to successful pregnancy, by inducing ARG1 and IRF4 transcription, which are implicated in normal pregnancy. The experiments on OVX mice have shown that pharmacological inhibition of E 2 promoted nuclear translocation of NF-κB in the decidual macrophages. Further more, pharmacological inhibition or knockdown of SGK1 in TLR4-stimulated THP-1 macrophages activated NF-κB by promoting its nuclear translocation, leading to increased secretion of pro-inflammatory cytokines involved in pregnancy loss. Conclusion Our findings highlighted the immunomodulatory roles of E 2 -activated SGK1 in Th2 immune responses by priming anti-inflammatory M2 macrophages at the maternal–fetal interface, resulting in a balanced immune microenvironment during pregnancy. Our results suggest new perspectives on future preventative strategies for RPL.

The ubiquitously expressed serum and glucocorticoid regulated kinase 1 (SGK1) is tightly regulated by osmotic and hormonal signals, including glucocorticoids and mineralocorticoids. Recently, SGK1 has been implicated as a signal hub for the regulation of sodium transport. SGK1 modulates the activities of multiple ion channels and carriers, such as epithelial sodium channel (ENaC), voltage-gated sodium channel (Nav1.5), sodium hydrogen exchangers 1 and 3 (NHE1 and NHE3), sodium-chloride symporter (NCC), and sodium-potassium-chloride cotransporter 2 (NKCC2); as well as the sodium-potassium adenosine triphosphatase (Na+/K+-ATPase) and type A natriuretic peptide receptor (NPR-A). Accordingly, SGK1 is implicated in the physiology and pathophysiology of Na+ homeostasis. Here, we focus particularly on recent findings of SGK1’s involvement in Na+ transport in renal sodium reabsorption, hormone-stimulated salt appetite and fluid balance and discuss the abnormal SGK1-mediated Na+ reabsorption in hypertension, heart disease, edema with diabetes, and embryo implantation failure.

The campus courtyards in the Lingnan area are commonly used spaces. Therefore, their thermal comfort is highly important for improving user satisfaction. This study conducted field research on 18 courtyards in four universities in Lingnan to explore the effects of their architectural design factors on the thermal environment. Relevant studies have proved that courtyards are cost-effective in microclimate regulation, and individual factors such as the scale and openness of the courtyards have also been shown to have an effect on the thermal comfort of the courtyards. This study synthesizes multidimensional architectural design factors to explore and analyze the thermal environments of college courtyards. Physiologically equivalent temperature (PET) is selected as the thermal comfort evaluation index for the study and the conclusions are as follows: (1) The thermal environment is the most important factor influencing visitors to the courtyards (22%), and good thermal comfort improves the efficiency of using the college courtyards; (2) the courtyards have a positive microclimate regulating function, and a cooling effect occurs in 80% of them; and (3) the floor location, type, orientation, and sky view factor (SVF) of the courtyards are the main design factors affecting the thermal environment and PET. The first three factors were negatively correlated with PET (p < 0.05),and SVF was positively correlated with PET (p = 0.651). Passive courtyard design strategies are presented based on the findings of this study.

Epidemiological studies have revealed that offspring conceived by in vitro fertilization (IVF) have an elevated risk of cardiovascular malformations at birth, and are more predisposed to cardiovascular diseases. The renin-angiotensin system (RAS) plays an essential role in both the pathogenesis of congenital heart disease in fetuses and cardiovascular dysfunction in adults. This study aimed to assess the relative expression levels of genes in the RAS pathway in mice conceived using IVF, compared to natural mating with superovulation. Results demonstrated that expression of the angiotensin II receptor type 1 (AGTR1), connective tissue growth factor (CTGF), and collagen 3 (COL3), in the myocardial tissue of IVF-conceived mice, was elevated at 3 weeks, 10 weeks, and 1.5 years of age, when compared to their non-IVF counterparts. These data were supported by microRNA microarray analysis of the myocardial tissue of aged IVF-conceived mice, where miR-100, miR-297, and miR-758, which interact with COL3, AGTR1, and COL1 respectively, were upregulated when compared to naturally mated mice of the same age. Interestingly, bisulfite sequencing data indicated that IVF-conceived mice exhibited decreased methylation of CpG sites in Col1. In support of our in vivo investigations, miR-297 overexpression was shown to upregulate AGTR1 and CTGF and increased cell proliferation in cultured H9c2 cardiomyocytes. These findings indicate that the altered expression of RAS in myocardial tissue might contribute to cardiovascular malformation and/or dysfunction in IVF-conceived offspring. Furthermore, these cardiovascular abnormalities might be the result of altered DNA methylation and abnormal regulation of microRNAs. Summary Sentence Altered expression of the renin-angiotensin system in myocardial tissue might contribute to an increased risk of cardiovascular malformations and dysfunction in IVF offspring, and is involved in abnormal regulations of DNA methylation and microRNAs.

An ectopic ureter is a ureter that does not correctly connect to the trigone of the bladder and drains outside of the bladder. Here, we presented five cases of ectopic ureter opening into the vagina, whose clinical symptoms and malformations were rarely described in previous case reports. All five patients were hospitalized with complaints of gynecologic disease. Three of the five cases did not present the typical symptoms of urinary incontinence. Three of these cases showed congenital malformations of the female genital tract. Four cases were diagnosed in adulthood. All patients were analyzed using various imaging examinations. This study suggests that the ectopic ureter should be considered in the differential diagnosis of a pelvic mass in a patient with urinary and reproductive system abnormalities. It is essential to comprehensively evaluate complex malformations of the genitourinary system with multiple imaging tests.

The physiological interactions between the peripheral and central auditory systems are crucial for auditory information transmission and perception, while reliable models for auditory neural circuits are currently lacking. To address this issue, mouse and human neural pathways are generated by utilizing a carbon nanotube nanofiber system. The super‐aligned pattern of the scaffold renders the axons of the bipolar and multipolar neurons extending in a parallel direction. In addition, the electrical conductivity of the scaffold maintains the electrophysiological activity of the primary mouse auditory neurons. The mouse and human primary neurons from peripheral and central auditory units in the system are then co‐cultured and showed that the two kinds of neurons form synaptic connections. Moreover, neural progenitor cells of the cochlea and auditory cortex are derived from human embryos to generate region‐specific organoids and these organoids are assembled in the nanofiber‐combined 3D system. Using optogenetic stimulation, calcium imaging, and electrophysiological recording, it is revealed that functional synaptic connections are formed between peripheral neurons and central neurons, as evidenced by calcium spiking and postsynaptic currents. The auditory circuit model will enable the study of the auditory neural pathway and advance the search for treatment strategies for disorders of neuronal connectivity in sensorineural hearing loss. The lack of therapeutic avenues for auditory neural pathway disorders is primarily attributed to inadequate research models. This study pioneers a novel auditory circuit model using super‐aligned carbon nanotubes. The peripheral‐central neural organoids with functional synaptic transmission facilitate the exploration of the auditory neural pathway and propel the quest for strategies for neuronal connectivity disorders in sensorineural hearing loss.

PurposeTo assess testicular mRNA and protein expression levels of MRE11 and RAD50 in human azoospermia patients.MethodsPatients diagnosed with maturation arrest at the spermatocyte stage (MA) and Sertoli cell-only syndrome (SCOS) were recruited through diagnostic testicular biopsy. Patients with normal spermatogenesis were studied as controls. In addition, knockdown of MRE11 and RAD50 was performed in GC-2spd(ts) cells to investigate their roles in cellular proliferation and apoptosis.ResultsmRNA and protein expression levels of MRE11 and RAD50 were measured using quantitative polymerase chain reaction, western blotting, and immunohistochemistry, respectively. Knockdown of both MRE11 and RAD50 utilized transfection with small interfering RNAs.ConclusionOur findings demonstrated altered expression levels of MRE11 and RAD50 in human testes with MA and SCOS, and showed that these alterations might be associated with impaired spermatogenesis. These results offer valuable new perspectives into the molecular mechanisms of male infertility.

Objective Organisms and cellular viability are of paramount importance to living creatures. Disruption of the balance between cell survival and apoptosis results in compromised viability and even carcinogenesis. One molecule involved in keeping this homeostasis is serum-glucocorticoid regulated kinase (SGK) 1. Emerging evidence points to a significant role of SGK1 in cell growth and survival, cell metabolism, reproduction, and life span, particularly in prenatal programming and reproductive senescence by the same token. Whether the hormone inducible SGK1 kinase is a major driver in the pathophysiological processes of prenatal programming and reproductive senescence? Method The PubMed/Medline, Web of Science, Embase/Ovid, and Elsevier Science Direct literature databases were searched for articles in English focusing on SGK1 published up to July 2023 Result Emerging evidence is accumulating pointing to a pathophysiological role of the ubiquitously expressed SGK1 in the cellular and organismal viability. Under the regulation of specific hormones, extracellular stimuli, and various signals, SGK1 is involved in several biological processes relevant to viability, including cell proliferation and survival, cell migration and differentiation. In line, SGK1 contributes to the development of germ cells, embryos, and fetuses, whereas SGK1 inhibition leads to abnormal gametogenesis, embryo loss, and truncated reproductive lifespan. Conclution SGK1 integrates a broad spectrum of effects to maintain the homeostasis of cell survival and apoptosis, conferring viability to multiple cell types as well as both simple and complex organisms, and thus ensuring appropriate prenatal development and reproductive lifespan.

Spontaneous abortion (SA) occurs in woman of child-bearing age, jeopardizing their physical and mental health. Quercetin is a natural flavonoid, which exhibits a variety of pharmacological activities. However, the role and mechanisms of quercetin in SA still need to be further explored. Animal experiments were performed to examine the effect of quercetin in treating SA. Institute of Cancer Research mice were injected with lipopolysaccharide into the tail vein on the 7th day of gestation to establish a SA model. Gavage was performed during days 3-8 of gestation with high-, medium- and low-dose of quercetin. Then the effect of quercetin on embryos was evaluated. Animal experiment showed that quercetin could remarkably reduce the embryo loss rate and increase the mean weight of surviving embryos to some degree. Furthermore, network pharmacology was employed to explore the underlying mechanisms of quercetin in the treatment of SA. Several databases were used to collect the targets of SA and quercetin. Protein-protein interaction network, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed to elucidate the interactions between SA and quercetin. The relative mRNA expressions of several targets in uterine were detected by quantitative reverse transcriptase polymerase chain reaction (RT-qPCR). Network pharmacology indicated that the effects of quercetin in treating SA were mainly related to hormone response and the modulation of defense response and inflammatory response, involving signaling pathways such as PI3K-Akt, VEGF, MAPK and core targets such as AKT1, albumin, caspase-3. RT-qPCR showed that quercetin could up-regulate AKT1, MAPK1, PGR, SGK1 and down-regulate ESR1, MAPK3. The results showed that quercetin may modulate multiple signaling pathways by targeting core targets to prevent and treat SA.