Reproductive Sciences最新文献

Orchitis is a frequent inflammatory reproductive disease that causes male infertility and a decline in sperm quality. Gut microbiota can regulate systemic and local inflammation, spermatogenesis and blood-testosterone barrier (BTB). In this study, we investigated correlation between gut microbiota and orchitis by establishing a mouse gut microbiota imbalance model induced by antibiotics (ABX) treatment and orchitis model induced by lipopolysaccharide (LPS) infection. Based on these two models, 16s rRNA sequencing and feces microbiota transplantation (FMT) experiments were combined to examine the function and regulatory mechanisms of the gut microbiota in host defense against orchitis. Compared with control mice, gut microbiota imbalance resulted in increasing inflammatory responses, modulating oxidative stress related enzyme activity, testosterone levels and the permeability of blood testosterone barrier, which are restored after FMT. Subsequently, we tested the relationship between the gut microbiota imbalance and testicular inflammation severity in orchitis. It was found that the ABX and LPS co-treated mice had more severe inflammatory responses, lower testosterone levels and greater permeability of the BTB than the LPS-treated mice, but these changes could be partially recovered by gut microbiota transplantation. In conclusion, these above results proved for the first time that gut microbiota is involved in the pathogenesis of orchitis, which laid a good foundation for the subsequent development of anti-orchitis drugs and probiotic targeting intestinal flora.

Cavernous hemangioma within the female genital tract is an extremely rare pathology, characterized by irregular vascular spaces containing blood or thrombus. We present a unique case of a 42-year-old primiparous woman who presented with typical endometriosis symptoms such as dysmenorrhea, dyspareunia, and heavy menstrual bleeding. The patient also experienced complex postpartum symptoms, which were misdiagnosed as cholecystitis and retained placental products. Imaging studies suggested deep infiltrative endometriosis with extraovarian endometriotic lesions. Surgical exploration revealed a hemangioma within the right anterior broad ligament alongside peritoneal endometriosis lesions. The hemangioma itself expresses estrogen and progesterone receptors in stromal cells. The presence of steroid hormone receptors strongly suggests symptom alleviation during the menstrual cycle and the postpartum period. The coexistence of cavernous hemangioma and endometriosis in the broad ligament, previously unreported, and symptomatic overlap between the two conditions complicates diagnosis and management, emphasizing the need for comprehensive evaluation integrating clinical symptoms and imaging findings.

Pulmonary arterial hypertension (PAH) is a disease that affects millions of people worldwide. Besides the effects on the lungs and heart, PAH can affect other organs, including the liver, kidneys, brain, glands, and testis. This study aimed to evaluate the impact of PAH and physical resistance training (RT), a complementary treatment for hypertension, on epididymis morphology and function and sperm parameters. Wistar rats were divided into four experimental groups (n = 8/ group): sedentary control, sedentary PAH, RT control, and RT + PAH. PAH was induced using monocrotaline injections on Day 1 and 7 of the experiment. Sixteen rats from RT groups underwent RT training for 30 days, while rats from sedentary groups did not exercise. The epididymis was processed and analyzed using microscopic, biochemical, and functional approaches. Sperm were harvested from the cauda epididymis and evaluated for morphology and motility. Our results showed that PAH compromised the epididymis antioxidant defense system and reduced NO levels, leading to an imbalance in the organ's mineral content. These alterations affected the epididymis morphology and reduced the sperm transit time in the proximal epididymis, resulting in an increase in abnormal sperm morphology in the cauda region. Unfortunately, RT was not a good therapy against the PAH effect on the epididymis. PAH negatively affected epididymis functions with consequences to male gametes. Dysfunctions in the post-testicular environment may lead to male infertility due to the disturbance of spermatozoa fecundity.

The aim of this study was to investigate the effects of miR-424-5p on biological behaviors and angiogenesis of the HTR-8/SVneo Cells. Our study included 60 parturient women, which were divided into an PA group (placenta accreta, n = 30) and a normal group (normal placenta, n = 30). QPCR was used to measure the expression of miR-424-5p in placental tissues. The effects of the miR-424-5p mimic on proliferation, migration, and invasion of human HTR-8/SVneo cells and angiogenesis were analyzed. The potential modulated relationship between miR-424-5p and low-density lipoprotein receptor-related protein-6 (LRP6) was demonstrated by luciferase assay. The expression of LRP6, β-catenin, matrix metalloproteinase-2 (MMP-2), placental growth factor (PGF) and vascular endothelial growth factor (VEGF) were measured by qPCR and Western blot assays. The expression of miR-424-5p in the PA group was significantly decreased than that in the normal group. The expression of miR-424-5p has negative correlation with blood loss. Upregulation of miR-424-5p significantly suppressed the cell proliferation, migration, and invasion of HTR-8/SVneo cells in vitro, as well as the tube formation of human umbilical vein endothelial cells (HUVECs). The luciferase assay demonstrated that LRP6 was a target of miR-424-5p. The expression of LRP6, β-catenin, MMP-2, PGF and VEGF were also decreased with upregulation of miR-424-5p (p < 0.05). The inhibitory effects of miR-424-5p on HTR-8/SVneo cells and angiogenesis were enhanced by downregulation of LRP6, but were reversed by upregulation of LRP6. The present study suggests that downregulation of miR-424-5p is related to the occurrence of PA. Enhancing miR-424-5p inhibits proliferation, migration, invasion and angiogenesis of the HTR-8/SVneo cells through targeting LRP6 mediated β-catenin, providing more insights about PA.

Polycystic ovary syndrome (PCOS) is a metabolic disease that affects the reproductive system, and its pathogenesis remains unresolved. Through the application of bioinformatics and molecular biology techniques, this study has identified a significant association between translocase of outer mitochondrial membrane 40 (TOMM40) and both PCOS and pan-cancers. The selection of PCOS biomarkers included TOMM40, which we found to be significantly decreased in the PCOS group both in vitro and in vivo, using molecular biology methods such as Western Blot as well as immunohistochemistry. Over-expression TOMM40 can rescue the effect on apoptosis rate and proliferation suppression induced by DHEA in KGN cells. TOMM40 as a biomarker for the diagnosis of PCOS. The pan-cancer analysis revealed an association between elevated TOMM40 expression in Uterine Corpus Endometrial Carcinoma and an unfavorable prognosis, while increased TOMM40 expression in six tumor types was linked to a favorable prognosis. Therefore, TOMM40 can be regarded as a promising biomarker for diagnosing both PCOS and pan-cancer.

Bisphenol AF (BPAF) is increasingly used and now found in products intended for human consumption. The protective effect of 1,8-cineole (CIN) against BPAF-induced reproductive toxicity was investigated. Four groups were created, with each group consisting of eight rats: control, BPAF (200 mg/kg), CIN (200 mg/kg), and BPAF + CIN groups. The results demonstrated that the BPAF group exhibited a decline in testosterone levels and a decrease in sperm parameters compared with the control. Additionally, higher levels of MDA were observed, along with lower levels of GSH and GPx activity. CAT activity also decreased slightly. Tnf-α, Nf-κB levels were significantly higher, and caspase-3 expression was elevated, while PCNA expression decreased. BPAF significantly increased tissue degeneration compared with the control. However, the BPAF + CIN group showed statistically significant improvements in sperm parameters, except for concentration. They also exhibited an increase in testosterone levels and an improvement in MDA and GSH levels compared with the BPAF group. However, GPx activity partially enhanced. Tnf-α and Nf-κB levels were significantly reduced, and caspase-3 levels declined while PCNA and Bcl-2 levels increased. The Johnsen Testicular Biopsy score showed a substantial increase. Overall, these results suggest that CIN co-treatment in rats enhanced reproductive health and exhibited antioxidant, antiapoptotic, and anti-inflammatory properties against BPAF-induced testicular damage.

Oligozoospermia is an important cause of male infertility for which treatment options are limited. Spermatogenesis is complex, and the causes of oligozoospermia remain largely unknown. Because genetic mutations are important factors of oligozoospermia pathogenesis, our study aimed to explore the genetic causes of oligozoospermia. Whole- exome sequencing (WES) was performed on one proband from a Chinese family who was diagnosed with oligozoospermia. The pathogenic mutations were confirmed by Sanger sequencing, and a minigene assay was used to determine the effect of the identified splicing mutation. We identified a novel compound heterozygous mutation in the TDRD9 gene, comprising a splicing mutation (c.1115 + 3A > G) and a frameshift mutation (c.958delC), in the proband; neither of these mutations were found in 50 unrelated healthy people. In addition, a minigene assay demonstrated that the frameshift produced partially truncated protein, and the splicing mutation led to a frameshift mutation and premature termination due to abnormal alternative splicing of TDRD9. These findings indicate that deleterious compound heterozygous mutation in TDRD9 could lead to oligozoospermia, highlighting the crucial role of TDRD9 in spermatogenesis and further clarifying the genetic causes of male infertility resulting from oligozoospermia. Our study expands the spectrum of TDRD9-related phenotypes and provides a new specific target for future genetic counseling.

Preeclampsia (PE) is the most common pregnancy-related complication responsible for maternal mortality and morbidity. PE pathogenesis is characterized by placental dysfunction, impaired invasion of trophoblast, and defective spiral artery remodelling. Even after many years of research on PE, the etiology and pathophysiology of PE is still elusive. Our earlier studies have shown deregulated maternal and placental fatty acid and lipid metabolism to be associated with the pathogenesis of PE. Currently available lipidomics data have shown that glycerophospholipids, sphingolipid and cholesterol metabolism are mainly altered in preeclampsia. Including these five metabolites (SM C28:1, SM C30:1, LPC C19:0, LPE C20:0, propane-1,3-diol) with currently used protein biomarkers like sFlt-1/PlGF will improve PE prediction. Similarly, CE17:1 and CER(d20:1/24:1) alongwith sFlt-1/PlGF makes a better prediction of PE than sFlt-1/PlGF alone A comprehensive map of lipid profiles in early pregnancy may provide an improved understanding of disease pathogenesis and will be useful predictive biomarkers. In this article, we aimed to summarize the significance of lipid metabolism in the preeclampsia pathogenesis and altered lipidome signatures in preeclampsia. We also discuss the future scope of lipidomics in aiding early prediction of PE and future cardiovascular risk in both mother and child.

It is urgent to develop new therapeutic strategies for ovarian cancer (OC). Long-noncoding RNAs (lncRNAs) have participated in multiple biological processes including tumor recurrence and progression. This study aimed to determine the effects and potential regulatory mechanism of lncRNA FOXD2-AS1 in OC progression. Levels of lncRNA FOXD2-AS1 and miR-324-3p in OC tissues and cell lines were analyzed using quantitative real-time PCR (qRT-PCR). The direct target between FOXD2-AS1 or miR-324-3p was determined using bioinformatics tools and further verified by dual-luciferase reporter assay. Cell viability, apoptosis, migration, along invasion were assessed by MTT, flow cytometry, as well as Transwell assays, respectively. In addition, the levels of miR-324-3p, PCNA, MMP9, Bax, Bcl-2, and SOX4 in OC cells were evaluated using qRT-PCR and western blot assays. We observed that lncRNA FOXD2-AS1 was up-regulated while miR-324-3p was down-regulated in OC tissues and cell lines, especially in SKOV3 cells. Moreover, miR-324-3p was a direct target of lncRNA FOXD2-AS1. Meanwhile, SOX4 interacted with miR-324-3p and was negatively regulated by miR-324-3p in SKOV3 cells. Function assays confirmed that lncRNA FOXD2-AS1 silenced depressed cell proliferation, migration, and invasion while accelerating apoptosis. These functions of lncRNA FOXD2-AS1 were attenuated by miR-324-3p inhibition. Our research demonstrated that FOXD2-AS1 silencing restrained cell growth and metastasis of OC via regulating miR-324-3p/SOX4 axis, indicating that lncRNA FOXD2-AS1 could be a novel potential therapeutic target for OC.