A disintegrin and metalloproteinase with thrombospondin-like motifs (ADAMTS) represent a diverse family of secreted metalloproteinases, comprising 19 distinct members categorized into five groups based on their substrate specificity: proteoglycanases, procollagen N-peptidases, von Willebrand factor-cleaving protease, cartilage oligomeric matrix proteases and other proteases. Among these, ADAMTS proteoglycanases predominantly target hyalectans, pivotal components in extracellular matrix (ECM) remodeling and inflammation. Dysfunction of ADAMTS proteoglycanases disrupts the structure and function of hyalectans, thereby perturbing ECM homeostasis, resulting in reproduction disorders, including abnormal follicular development, ovulation dysfunction, impaired implantation, placentation and preterm labor. Hence, investigation of the role of ADAMTS proteoglycanases offers valuable insights into the molecular mechanisms underlying the physiological or pathological processes within the female reproductive system, thereby paving the way for innovative strategies in predicting, preventing and treating reproductive system diseases. This review summarizes the recent research advances in the structure and regulation of ADAMTS proteoglycanases and their role in female reproductive system.
Humans ; Female ; ADAMTS Proteins/physiology* ; ADAM Proteins/physiology* ; Pregnancy ; Animals ; Genitalia, Female/enzymology* ; Extracellular Matrix/metabolism*

Objective To investigate the effect and mechanism of baicalin on blood lipid metabolism and immune function in rats with gestational diabetes mellitus (GDM). Methods Female rats fed with high-fat and high-sugar diet and male rats fed with ordinary diet were caged together to prepare pregnant rats, and the GDM rat model was established by intraperitoneal injection of streptozotocin (35 mg/kg). GDM rats were randomly divided into a model group, a fasudil (FA) (RhoA/RocK inhibitor) group (10 mg/kg), low-dose (100 mg/kg) and high-dose (200 mg/kg) baicalin groups, and a high-dose baicalin combined with LPA (RhoA/RocK activator) group (200 mg/kg baicalin+1 mg/kg LPA ), with 12 rats in each group. Another 12 pregnant rats fed with high-fat and high-sugar diet were selected as the control group. After 2 weeks of corresponding drug intervention in each group, the level of fasting blood glucose (FBG) was detected by blood glucose meter. The level of fasting insulin (FINS) in serum was detected by ELISA, and the insulin resistance index (HOMA-IR) was calculated. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) in serum, and the levels of immunomodulator tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and IL-10 in peripheral blood were detected by the kit. The histopathological changes of liver were observed by HE staining. The proportion of T lymphocyte subsets in peripheral blood was detected by flow cytometry. The mRNA and protein expressions of Ras homolog gene family member A (RhoA), Rho associated coiled-coil forming protein kinase 1 (ROCK1), and ROCK2 in liver tissue were detected by real-time quantitative PCR and Western blot. Results Compared with the control group, the levels of FBG, FINS, HOMA-IR, ALT, AST, TG, TC, and LDL-C in serum, the levels of TNF-α, IL-6, the percentage of CD8⁺T cell in peripheral blood, and the mRNA and protein expression of RhoA, ROCK1, and ROCK2 in liver tissue in the model group were higher; the level of HDL-C in serum, the percentage of IL-10 levels, CD3⁺T cells, CD4⁺T cell, and CD4⁺T/CD8⁺T ratio in peripheral blood were lower. Compared with the model group, the levels of FBG, FINS, HOMA-IR, ALT, AST, TG, TC, and LDL-C in serum, the levels of TNF-α, IL-6, the percentage of CD8⁺T cell in peripheral blood, and the mRNA and protein expression of RhoA, ROCK1, and ROCK2 in liver tissue in the the FA group and low-dose and high-dose baicalin groups were lower; the level of HDL-C in serum, IL-10 level, the percentage of CD3⁺T cells, CD4⁺T cell, and CD4⁺T/CD8⁺T ratio in peripheral blood were higher. LPA could obviously weaken the improvement effects of baicalin on blood lipid metabolism and immune function in GDM rats. Conclusion Baicalin may improve blood lipid metabolism and immune function in GDM rats by inhibiting the RhoA/ROCK pathway.
Animals ; Female ; Diabetes, Gestational/metabolism* ; Pregnancy ; rho-Associated Kinases/genetics* ; Flavonoids/pharmacology* ; Rats ; rhoA GTP-Binding Protein/genetics* ; Lipid Metabolism/drug effects* ; Male ; Signal Transduction/drug effects* ; Rats, Sprague-Dawley ; Blood Glucose/metabolism* ; Lipids/blood* ; Tumor Necrosis Factor-alpha/blood* ; rho GTP-Binding Proteins

Primary ciliary dyskinesia (PCD) is a clinically rare, genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections, male infertility, tympanitis, and laterality abnormalities. PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia. Here, we identified a novel nonsense mutation, c.466G>T, in cilia- and flagella-associated protein 300 ( CFAP300 ) resulting in a stop codon (p.Glu156*) through whole-exome sequencing (WES). The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm (IDA) and outer dynein arm (ODA). Bioinformatic programs predicted that the mutation is deleterious. Successful pregnancy was achieved through intracytoplasmic sperm injection (ICSI). Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.
Adult ; Female ; Humans ; Male ; Pregnancy ; China ; Ciliary Motility Disorders/genetics* ; Codon, Nonsense ; East Asian People/genetics* ; Exome Sequencing ; Homozygote ; Infertility, Male/genetics* ; Kartagener Syndrome/genetics* ; Pedigree ; Sperm Injections, Intracytoplasmic ; Cytoskeletal Proteins/genetics*

Azoospermia, defined as the absence of sperm in the ejaculate, is a well-documented consequence of exogenous testosterone (ET) and anabolic-androgenic steroid (AAS) use. These agents suppress the hypothalamic-pituitary-gonadal (HPG) axis, leading to reduced intratesticular testosterone levels and impaired spermatogenesis. This review examines the pathophysiological mechanisms underlying azoospermia and outlines therapeutic strategies for recovery. Azoospermia is categorized into pretesticular, testicular, and post-testicular types, with a focus on personalized treatment approaches based on the degree of HPG axis suppression and baseline testicular function. Key strategies include discontinuing ET and monitoring for spontaneous recovery, particularly in patients with shorter durations of ET use. For cases of persistent azoospermia, gonadotropins (human chorionic gonadotropin [hCG] and follicle-stimulating hormone [FSH]) and selective estrogen receptor modulators (SERMs), such as clomiphene citrate, are recommended, either alone or in combination. The global increase in exogenous testosterone use, including testosterone replacement therapy and AAS, underscores the need for improved management of associated azoospermia, which can be temporary or permanent depending on individual factors and the type of testosterone used. Additionally, the manuscript discusses preventive strategies, such as transitioning to short-acting testosterone formulations or incorporating low-dose hCG to preserve fertility during ET therapy. While guidelines for managing testosterone-related azoospermia remain limited, emerging research indicates the potential efficacy of hormonal stimulation therapies. However, there is a notable lack of well-structured, controlled, and long-term studies addressing the management of azoospermia related to exogenous testosterone use, highlighting the need for such studies to inform evidence-based recommendations.
Humans ; Azoospermia/therapy* ; Male ; Testosterone/therapeutic use* ; Anabolic Agents/adverse effects* ; Clomiphene/therapeutic use* ; Chorionic Gonadotropin/therapeutic use* ; Follicle Stimulating Hormone/therapeutic use* ; Spermatogenesis/drug effects* ; Androgens/adverse effects*

OBJECTIVE: To study the clinical efficacy of Wenyang Lishui Formula (WYLSF) in preventing ovarian hyperstimulation syndrome (OHSS) and explore the suitable range of estradiol (E₂) on the human chorionic gonadotropin (HCG) day in patients with OHSS using WYLSF. METHODS: Part I: eligible patients at high risk for OHSS undergoing ovulation induction between January and December, 2023 were randomized into 2 groups based on the actual treatment. The treatment group received 200 mL WYLSF formula twice daily for 5 days after oocyte retrieval in a combination of lifestyle coaching (LC) intervention including regular diet and exercise, whereas the LC group received LC intervention alone. The incidence of OHSS, OHSS self-assessment scales, changes in E₂ levels on HCG day and 5 days after oocyte retrieval, ovarian morphology changes, and menstrual recovery were compared between the two groups. Part II: patients at high risk for OHSS treated with WYLSF were studied. The optimal E₂ threshold on the HCG day was determined using the maximum selection test, and a multivariate analysis was adopted to compare the relationship between different E₂ levels on HCG day and hospitalization rate, incidence of moderate to severe OHSS, and self-assessment scales, to explore the preventive effect of WYLSF on OHSS in patients with varying E₂ levels. RESULTS: A total of 120 patients were included in the Part I analysis. The treatment group (60 cases) showed a significant reduction in the incidence, duration, and severity of abdominal distension, as well as the incidence of vomiting compared with the LC group (P<0.05). The post-retrieval E₂ levels in the treatment group decreased significantly more (P=0.032). Among 1,652 patients treated with WYLSF in the Part II, 90 patients with ⩽ 10092 pmol/L, 159 with >31074 pmol/L, and 1,403 in the middle range group were formed based on E₂ levels on HCG day in Part two analysis. Univariate and regression analyses showed that patients with E₂ levels >31073 pmol/L had a significantly higher incidence of moderate to severe OHSS compared to those with E₂ levels ⩽ 10092 pmol/L (P<0.05). CONCLUSIONS WYLSF can effectively reduce specific symptoms in high-risk OHSS patients after ovulation induction and significantly lower E₂ levels. It may be more suitable for high-risk OHSS patients with E₂ levels <31073 pmol/L on HCG day. (Registration No. MR-11-23-032493, https://www.medicalresearch.org.cn/login ).
Humans ; Ovarian Hyperstimulation Syndrome/blood* ; Female ; Adult ; Prospective Studies ; Drugs, Chinese Herbal/pharmacology* ; Estradiol/blood* ; Ovulation Induction ; Chorionic Gonadotropin

Atypical placental site nodules (APSN) are a rare form of trophoblastic disease in pregnancy. There is limited research on APSN, and treatment methods are controversial, with unclear prognosis. This study collected clinical and prognostic data of 5 patients diagnosed with APSN at Xiangya Hospital of Central South University from June 2008 to June 2023, aiming to provide a better understanding of the prognosis of APSN patients and offer scientific evidence for clinical treatment. The average age of the 5 APSN patients was 32.60 years, and all patients underwent dilation and curettage or hysteroscopic surgery or hysteroscopic surgery without hysterectomy. Except for one patient who was lost to follow-up after 30 days, the remaining 4 patients were followed up for 1.36 to 4.61 years. During the follow-up, gynecological ultrasound did not show abnormalities, and serum human chorionic gonadotropin (HCG) tests were negative, with no evidence of malignancy. A search of both English and Chinese databases yielded 8 articles reporting the diagnosis, treatment, and follow-up outcomes of APSN, with 37 cases cumulatively followed up. Among them, 2 (5.41%) cases developed epithelial trophoblastic tumors or placental site trophoblastic tumors during follow-up, but there is insufficient evidence to determine whether these tumors directly originated from APSN or were secondary to APSN. Currently, there is no direct evidence suggesting that APSN has the potential for malignant transformation. Patients with APSN who have completed their childbearing may consider preserving their uterus, but close follow-up is needed to further evaluate the prognosis.
Humans ; Female ; Pregnancy ; Adult ; Trophoblastic Tumor, Placental Site/pathology* ; Uterine Neoplasms/diagnosis* ; Prognosis ; Dilatation and Curettage ; Chorionic Gonadotropin/blood*

OBJECTIVES: To explore the effects of exogenous trigger (hCG/GnRHa) versus endogenous LH surge in natural cycle IVF/ICSI (NC-IVF/ICSI) for patients with diminished ovarian reserve (DOR). METHODS: A retrospective analysis was conducted on 1,118 NC-IVF/ICSI cycles from two reproductive centers between 2013 and 2024. Propensity score matching (PSM) and multivariate logistic regression were used to adjust for confounding factors. The trigger-day hormone threshold was determined using receiver operating characteristic (ROC) curve analysis. Outcome measures included oocyte retrieval rate, 2PN fertilization rate, clinical available embryo rate, high-quality embryo rate, fresh cycle clinical pregnancy rate (CPR), and live birth rate (LBR). RESULTS: After adjusting for confounders via PSM and logistic regression, the exogenous trigger group demonstrated significantly better outcomes across all the evaluated parameters (oocyte retrieval rate, 2PN fertilization rate, transferable embryo rate, high-quality embryo rate, fresh cycle CPR, and LBR) than the endogenous LH surge group (P<0.05). Age-stratified analysis revealed that for the entire cohort, exogenous triggering significantly increased the number of transferable embryos and high-quality embryos (P<0.001). In the 35-39 years old subgroup, exogenous triggering showed significant advantages in oocyte yield, high-quality embryo rate, CPR, and LBR (P<0.05) and resulted in the most pronounced improvement in LBR (OR=6.25, 95% CI: 1.34-29.23). ROC analysis established a decision-day LH threshold of 19.055 mIU/mL (AUC=0.945, specificity=93.3%) for precise stratification of the clinical pathways. CONCLUSIONS For DOR patients undergoing NC-IVF/ICSI, exogenous triggering comprehensively improves the treatment outcomes, particularly providing significant live birth benefits for women aged 35-40 years. An individualized protocol incorporating the LH threshold (19.055 mIU/mL) effectively enhances embryonic developmental potential and live birth rates.
Humans ; Female ; Ovarian Reserve ; Pregnancy ; Propensity Score ; Retrospective Studies ; Fertilization in Vitro ; Sperm Injections, Intracytoplasmic ; Chorionic Gonadotropin ; Pregnancy Rate ; Logistic Models ; Ovulation Induction/methods* ; Gonadotropin-Releasing Hormone ; Adult ; Oocyte Retrieval

Objective:By conducting genetic testing of hereditary hearing loss in pregnant women within 17 weeks of gestation in Dali areas, the importance of genetic testing and genetic counseling during pregnancy was emphasized. Methods:Twenty-one mutation sites of 4 hearing loss genes, including GJB2, GJB3, SLC26A4 and mtDNA, were detected by PCR amplification technology. The positive ratio, mutation ratio and ethnic distribution of positive samples were statistically described. Results:The positive ratios of GJB2 and SLC26A4 genes were 1.24% and 1.43%, respectively, with mutation rates of 40.62% and 46.88% in the positive samples, respectively. The positive ratio of GJB3gene was 0.19%, and mtDNA mutation genes accounted for 0.14%, and all of them were mtDNA（Heterozygous）. There was only one case of GJB2/SLC26A4 double positive multi-gene mutation, with a positive ratio of 0.05%. The frequency of GJB2 c. 235delC site was the highest, accounting for 65.38% of GJB2 mutation genes and 26.56% of mutation gene samples. Conclusion:GJB2 and SLC26A4 are the most common genes of hearing loss, and GJB2 c. 235delC site is the most common mutation site. Identifying the hearing loss mutation site is of great importance to prevent the birth of hereditary hearing loss children, and genetic diagnosis, genetic counseling, and appropriate intervention are crucial to alleviate congenital problems.
Humans ; Female ; Pregnancy ; Sulfate Transporters/genetics* ; Connexin 26 ; Genetic Testing/methods* ; Connexins/genetics* ; Mutation ; Hearing Loss/diagnosis* ; DNA, Mitochondrial/genetics* ; Adult ; Membrane Transport Proteins/genetics* ; Genetic Counseling

OBJECTIVE: To observe the effects of electroacupuncture (EA) on NLRP3 inflammasome and its downstream protein gastermin D (GSDMD) in rats with primary dysmenorrhea (PDM), and to explore the potential mechanism of EA on the treatment of PDM. METHODS: Forty healthy female SD rats without pregnancy were randomly divided into a control group, a model group, an EA group and an ibuprofen group, 10 rats in each group. PDM model was prepared by injection of estradiol benzoate and oxytocin. Except the control group, the rats in each group were subcutaneously injected with estradiol benzoate for 10 days, and oxytocin was injected on the 11th day. The rats in the EA group were intervened with EA (dense wave, frequency of 50 Hz) at "Guanyuan" (CV 4) and "Sanyinjiao" (SP 6) at the same time of modeling, once a day, 20 min each time, for 10 consecutive days. The rats in the ibuprofen group were treated with 0.8 mL of ibuprofen by gavage (concentration of ibuprofen solution was 1.25 mg/mL) for 10 consecutive days. After modeling, the writhing reaction was observed. After intervention, the HE staining method was used to observe the histological morphology of uterus and evaluate the pathological damage score of uterus; ELISA method was used to detect the serum levels of prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α); Western blot method was used to detect the protein expression of NLRP3, apoptosis related spot like protein (ASC), caspase-1, GSDMD, GSDMD-N and inflammatory factors (interleukin [IL]-1β, IL-18) in uterine tissue. RESULTS: In the model group, a large number of vacuolar degeneration and death of endometrial epithelial cells, spiral arterioles congestion in lamina propria and neutrophil infiltration were observed. In the EA group, there was a small amount of vacuolar degeneration and death of endometrial epithelial cells, a small amount of spiral arterioles congestion in the lamina propria, and a small amount of neutrophils infiltration. In the ibuprofen group, there was very small number of degeneration and death of endometrial epithelial cells, and no obvious arterial congestion was found in lamina propria, and neutrophil infiltration was occasionally seen. Compared with the control group, in the model group the number of writhing was increased (P<0.01), the writhing reaction score and serum level of PGF2α and PGF2α/PGE2 value were increased (P<0.01), the level of PGE2 was decreased (P<0.01). Compared with the model group, in the EA group and the ibuprofen group the number of writhing were decreased (P<0.05), the latency of writhing was prolonged (P<0.01), the writhing reaction scores and serum levels of PGF2α and PGF2α/PGE2 values were decreased (P<0.05, P<0.01), the levels of PGE2 were increased (P<0.01). Compared with the control group, the protein expression of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1β and IL-18 in the uterine tissues of rats was increased in the model group (P<0.01). Compared with the model group, the protein expression of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1β and IL-18 in the uterine tissues of rats was decreased in the EA group and the ibuprofen group (P<0.01, P<0.05). There was no significant difference between the EA group and the ibuprofen group in the above indexes (P>0.05). CONCLUSION EA could alleviate pain and uterine tissue injury in rats with PDM. The mechanism may be related to the inhibition of the activation of NLRP3 inflammasome in rat uterine tissues, thereby inhibiting pyroptosis and its inflammatory factors release.
Animals ; Female ; Pregnancy ; Rats ; Caspases ; Dinoprost ; Dinoprostone ; Dysmenorrhea ; Electroacupuncture ; Ibuprofen ; Inflammasomes ; Interleukin-18 ; NLR Family, Pyrin Domain-Containing 3 Protein ; Oxytocin ; Phosphate-Binding Proteins ; Pyroptosis ; Rats, Sprague-Dawley ; Uterus

OBJECTIVE: To explore the genetic basis for a child with Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities (NEDASB). METHODS: A child with NEDASB who presented at the Third Affiliated Hospital of Zhengzhou University in July 2021 was selected as the subject. Peripheral blood samples of the child and her parents were collected and subjected to high-throughput sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child was found to harbor a heterozygous c.820_828delinsCTTCA (p.Thr274Leufs*121) variant of the NOVA2 gene, for which both of her parents were of wild type. The variant was predicted as pathogenic based on the guidelines from the American College of Medical Genetics and Genomics. CONCLUSION The heterozygous c.820_828delinsCTTCA (p.Thr274Leufs*121) variant of the NOVA2 gene probably underlay the disease in this child. Above finding has enriched the spectrum of NOVA2 gene variants and provided a basis for genetic counseling and prenatal diagnosis for this family.
Child ; Female ; Humans ; Pregnancy ; Autistic Disorder/genetics* ; Brain ; Computational Biology ; Genetic Counseling ; Mutation ; Nerve Tissue Proteins/genetics* ; Neuro-Oncological Ventral Antigen ; Neurodevelopmental Disorders ; RNA-Binding Proteins