Kinesin KIFC3 is essential for microtubule stability and cytokinesis in oocyte meiosis.

KIFC3 is a member of Kinesin-14 family motor proteins, which play a variety of roles such as centrosome cohesion, cytokinesis, vesicles transportation and cell proliferation in mitosis. Here, we investigated the functional roles of KIFC3 in meiosis. Our findings demonstrated that KIFC3 exhibited expression and localization at centromeres during metaphase I, followed by translocation to the midbody at telophase I throughout mouse oocyte meiosis. Disruption of KIFC3 activity resulted in defective polar body extrusion. We observed aberrant meiotic spindles and misaligned chromosomes, accompanied by the loss of kinetochore-microtubule attachment, which might be due to the failed recruitment of BubR1/Bub3. Coimmunoprecipitation data revealed that KIFC3 plays a crucial role in maintaining the acetylated tubulin level mediated by Sirt2, thereby influencing microtubule stability. Additionally, our findings demonstrated an interaction between KIFC3 and PRC1 in regulating midbody formation during telophase I, which is involved in cytokinesis regulation. Collectively, these results underscore the essential contribution of KIFC3 to spindle assembly and cytokinesis during mouse oocyte meiosis.

Application of mesenchymal stem cell therapy for premature ovarian insufficiency: Recent advances from mechanisms to therapeutics.

The incidence of premature ovarian insufficiency (POI) is increasing worldwide, particularly among younger women, posing a significant challenge to fertility. In addition to menopausal symptoms, POI leads to several complications that profoundly affect female reproductive function and overall health. Unfortunately, current clinical treatment strategies for this condition are limited and often yield unsatisfactory outcomes. These approaches typically involve hormone replacement therapy combined with psychological support. Recently, mesenchymal stem cell (MSC) therapies for POI have garnered considerable attention in global research. MSCs can restore ovarian reproductive and endocrine functions through diverse mechanisms, including controlling differentiation, promoting angiogenesis, regulating ovarian fibrosis, inhibiting apoptosis, enhancing autocrine and paracrine effects, suppressing inflammation, modulating the immune system, and genetic regulation. This editorial offers a succinct summary of the application of MSC therapy in the context of POI, providing evidence for groundbreaking medical approaches that have potential to enhance reproductive health and overall well-being for women.

Mechanisms of Bushen Tiaoxue Granules against controlled ovarian hyperstimulation-induced abnormal morphology of endometrium based on network pharmacology.

Bushen Tiaoxue Granules (BTG) is an empirical Chinese herbal formula that has been used for the treatment of subfertility. The protective effect of BTG on controlled ovarian hyperstimulation (COH)-induced impaired endometrial receptivity has been reported in our previous study. This study aims to explore the mechanisms of BTG on ameliorating abnormal morphology of endometrium based on network pharmacology. Active compounds of BTG were identified via the traditional Chinese medicine systems pharmacology and UPLC-MS technology. The SwissTargetPrediction platform and HERB database were used to screen out the putative targets of BTG. Potential targets of endometrial dysfunction caused by COH were obtained from three GEO databases. Through the STRING database, the protein-protein interaction was carried out according to the cross-common targets of diseases and drugs. GO terms and KEGG pathways enrichment analyses were conducted via the Metascape database. AutoDock Vina was used for docking validation of the affinity between active compounds and potential targets. Finally, in vivo experiments were used to verify the potential mechanisms derived from network pharmacology study. A total of 141 effective ingredients were obtained from TCMSP and nine of which were verified in UPLC-MS. Six genes were selected through the intersection of 534 disease related genes and 165 drug potential targets. Enrichment analyses showed that BTG might reverse endometrial dysfunction by regulating adherens junction and arachidonic acid metabolism. Hematoxylin-eosin staining revealed that BTG ameliorated the loose and edematous status of endometrial epithelium caused by COH. The protein expression of FOXO1A, ß-Catenin and COX-2 was decreased in the COH group, and was up-regulated by BTG. BTG significantly alleviates the edema of endometrial epithelium caused by COH. The mechanisms may be related to adheren junctions and activation of arachidonic acid metabolism. The potential active compounds quercetin, taxifolin, kaempferol, eriodictyol, and isorhamnetin identified from the BTG exhibit marginal cytotoxicity. Both high and low concentrations of kaempferol, eriodictyol, and taxifolin are capable of effectively ameliorating impaired hESC cellular activity.

NAMPT regulates mitochondria function and lipid metabolism during porcine oocyte maturation.

Oocyte maturation defect can lead to maternal reproduction disorder. NAMPT is a rate-limiting enzyme in mammalian NAD+ biosynthesis pathway, which can regulate a variety of cellular metabolic processes including glucose metabolism and DNA damage repair. However, the function of NAMPT in porcine oocytes remains unknown. In this study, we showed that NAMPT involved into multiple cellular events during oocyte maturation. NAMPT expressed during all stages of porcine oocyte meiosis, and inhibition of NAMPT activity caused the cumulus expansion and polar body extrusion defects. Mitochondrial dysfunction was observed in NAMPT-deficient porcine oocytes, which showed decreased membrane potential, ATP and mitochondrial DNA content, increased oxidative stress level and apoptosis. We also found that NAMPT was essential for spindle organization and chromosome arrangement based on Ac-tubulin. Moreover, lack of NAMPT activity caused the increase of lipid droplet and affected the imbalance of lipogenesis and lipolysis. In conclusion, our study indicated that lack of NAMPT activity affected porcine oocyte maturation through its effects on mitochondria function, spindle assembly and lipid metabolism.

Burden and attributable risk factors of ischemic stroke in China from 1990 to 2019: an analysis from the Global Burden of Disease Study 2019.

Background: The epidemiologic characteristics and attributable risk factors of ischemic stroke in China have changed over the past three decades. An up-to-date analysis on deaths, disability-adjusted life-years (DALYs), prevalence, incidence, and attributable risk factors of ischemic stroke for China is needed. This study aims to provide a comprehensive analysis of burden and attributable risk factors of ischemic stroke at national level in China by sex from 1990 to 2019. Methods: This is a secondary analysis of the Global Burden of Disease (GBD) study 2019. All data used in this study was derived from the 2019 GBD study. Deaths, DALYs, prevalence, incidence, and attributable risk factors of ischemic stroke in China by sex from 1990 to 2019 were analyzed. Results: From 1990 to 2019, the age-standardized deaths rate decreased by 3.3%, age-standardized DALYs rate decreased by 4%, age-standardized prevalence rate increased by 33.5%, and age-standardized incidence rate of ischemic stroke in China increased by 34.7%. In 2019, ambient particulate matter pollution became an important risk factor, whereas household air pollution from solid fuels was no longer a major risk factor for ischemic stroke in China. Burden of ischemic stroke was higher in China compared to other regions. Ambient particulate matter pollution among men, and diet high in sodium, smoking, household air pollution from solid fuels among women account for the increased deaths/DALYs due to ischemic stroke in China. Conclusion: Our study revealed that great changes have occurred in burden and attributable risk factors of ischemic stroke in China in the past three decades. Distinct sex-specific differences are observed in burden and attributable risk factors.

Exposure to acrylamide induces zygotic genome activation defects of mouse embryos.

Acrylamide (ACR) is an important chemical raw material for wastewater treatment, paper industry and textile industry, which is widely exposed from occupational, environmental and dietary situation. ACR has neurotoxicity, genotoxicity, potential carcinogenicity and reproductive toxicity. Recent study indicates that ACR affected oocyte maturation quality. In the present study, we reported the effects of ACR exposure on zygotic genome activation (ZGA) in embryos and its related mechanism. Our results showed that ACR treatment caused 2-cell arrest in mouse embryos, indicating the failure of ZGA, which was confirmed by decreased global transcription levels and aberrant expression of ZGA-related and maternal factors. We found that histone modifications such as H3K9me3, H3K27me3 and H3K27ac levels were altered, and this might be due to the occurrence of DNA damage, showing with positive γ-H2A.X signal. Moreover, mitochondrial dysfunction and high levels of ROS were detected in ACR treated embryos, indicating that ACR induced oxidative stress, and this might further cause abnormal distribution of endoplasmic reticulum, Golgi apparatus and lysosomes. In conclusion, our results indicated that ACR exposure disrupted ZGA by inducing mitochondria-based oxidative stress, which further caused DNA damage, aberrant histone modifications and organelles in mouse embryos.

A modified mouse model of haemorrhagic transformation associated with tPA administration after thromboembolic stroke.

Objective: To establish a new mouse model of haemorrhagic transformation associated with delayed tissue-type plasminogen activator (tPA) treatment to provide a novel tool to study therapeutic strategies for haemorrhagic transformation. Methods: Male C57BL/6 mice were subjected to carotid artery thrombosis stimulated with ferric chloride. The thrombus was then mechanically detached to induce migration toward the intracranial circulation. To induce haemorrhagic transformation, mice were intravenously injected with 10 mg/kg tPA 4.5 h after the onset of ischaemia and were sacrificed 24 h after tPA treatment. Results: In this new model, administration of tPA 4.5 h after stroke exacerbated the risk of intracerebral haemorrhage. Thrombolysis with tPA also exacerbated cerebral infarction, brain oedema, blood-brain barrier breakdown, and neurological deficits. However, cerebral blood flow was not significantly affected. Conclusion: The present model is reproducible, easy to perform, and mimics the clinical situation of haemorrhagic transformation after tPA treatment in humans. This modified model can be used as a new tool to test experimental drugs for haemorrhagic transformation associated with delayed tPA administration after an ischaemic stroke.

Underlying mechanisms of acupuncture therapy on polycystic ovary syndrome: Evidences from animal and clinical studies.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder among women of reproductive age. Current standard treatment includes lifestyle change, oral pharmacological agents, and surgical modalities. However, the efficacy of current therapies is less than satisfactory. Clinical evidence has shown that acupuncture is effective for regulating hormone levels, promoting ovulation, and attenuating insulin resistance in patients with PCOS. Acupuncture may affect the production of ß-endorphin, which may lead to gonadotropin-releasing hormone secretion and then affect ovulation, menstrual cycle, and fertility. The mechanism of acupuncture for patients with PCOS has not been comprehensively reviewed so far. Better understanding of the mechanisms of acupuncture would help popularize the use of acupuncture therapy for patients with PCOS. In this narrative review, we aimed to overview the potential mechanisms and evidence-based data of acupuncture on PCOS, and analyze the most frequently used acupoints based on animal and clinical studies. The results of this study will contribute to a better understanding of the current situation in this field.

Improvement of two Mn2+ coordination polymers on cognitive function of aged rats after anesthesia.

Two Mn2+ coordination polymers (CPs) with the scientific terms of {[Mn(TTPA)·(H2O)2]·H2O} n (1) and {[Mn(TTPA)·(H2TTPA)]·2DMSO} n (2) were favorably created on the basis of multidentate linking organic ligand 2,5-bis-(1,2,4-triazol-1-yl)-terephthalic acid (H2TTPA) in the conditions of solvent-presupposed thermal reaction. To measure the influence of two Mn2+ coordination polymers with novel structures, the ELISA assay and real-time RT-PCR assay were conducted in this present research. First of all, the ELISA assay was conducted to measure the content of inflammatory cytokines released into the hippocampal tissue. In addition to this, the relative expression of the TAU protein in the brain was further determined with real-time RT-PCR assay.

High-dose zearalenone exposure disturbs G2/M transition during mouse oocyte maturation.

Zearalenone is a mycotoxin produced by fungi of the genus Fusarium, which has severe toxicity on animal and human health including reproduction. Previous study showed that zearalenone exposure inhibited oocyte polar body extrusion, while in present study we found that high dose zearalenone disturbed oocyte meiosis resumption. Our results showed that a high concentration of 100 µM zearalenone reduced the rate of germinal vesicle (GV) breakdown in mouse oocytes. Further analysis indicated that zearalenone caused the decrease of Cyclin B1 and CDK1 expression, indicating MPF activity was affected, which further induced G2/M arrest, and this could be rescued by the inhibition of Wee1 activity. We found that the oocytes under high concentration of zearalenone showed lower γ-H2A.X expression, suggesting that DNA damage repair was disturbed, which further activated of DNA damage checkpoints. This could be confirmed by the altered expression of CHK1 and CHK2 after zearalenone treatment. Moreover, the organelles such as mitochondria, ribosome, endoplasmic reticulum and Golgi apparatus were diffused from germinal vesicle periphery after zearalenone exposure, indicating that zearalenone affected protein synthesis, modification and transport, which further induced the arrest of G2/M transition. Taken together, our results showed that high dose of zearalenone exposure induced G2/M transition defect by affecting organelle function-related CHK1/2-Wee1-MPF pathway.

Efficacy of Chinese herbal medicine for tPA thrombolysis in experimental stroke: A systematic review and meta-analysis.

BACKGROUND: Tissue-type plasminogen activator (tPA) remains the sole FDA approved thrombolytic drug for ischemic stroke. But delayed thrombolytic therapy with tPA may increase the risk of hemorrhagic transformation. Many Chinese herbal medicines have been used as tPA helpers to enhance the capacity of tPA and minimize the risk of hemorrhagic transformation. The efficacy of Chinese herbal medicines on tPA thrombolysis is not systematically analyzed. METHODS: We searched the following three databases up to January 2022: Web of Science, PubMed, and Scopus. Studies that reported the efficacy and safety of Chinese herbal medicines on tPA thrombolysis in experimental stroke were included. The efficacy outcomes were neurological score and infarct volume, the safety outcomes were cerebral hemorrhage and blood brain barrier (BBB) damage. We used the checklist of CAMARADES to assess the quality of included studies. Standardized mean difference (SMD) with 95% confidence intervals were used to assess all the outcomes. Subgroup analyses were performed to explore the sources of heterogeneity. Trim and fill method and Egger's test were used to assess the potential publication bias. Sensitivity analyses were used to identify the stability of the results. RESULTS: A total of nine studies including 11 Chinese herbal medicines fulfilled the inclusion criteria and were subsequently analyzed. The pooled data demonstrated that Chinese herbal medicines improved neurological score (2.23 SMD, 1.42-3.04), infarct volume (1.08 SMD, 0.62-1.54), attenuated cerebral hemorrhage (1.87 SMD, 1.34-2.4), and BBB dysfunction (1.9 SMD, 1.35-2.45) following tPA thrombolysis in experimental stroke. Subgroup analysis indicated that the route of drug delivery, dosage of tPA, and stroke model used may be factors inducing heterogeneity and influencing the efficacy. CONCLUSION: Treatment with Chinese herbal medicines significantly improved neurological score and infarct volume, reduced cerebral hemorrhage and BBB damage after tPA thrombolysis. This study supports Chinese herbal medicine as an adjuvant therapy in reducing the side effects of tPA thrombolysis after acute ischemic stroke. The results should be interpreted with more caution since this article was based on animal studies.

Kinesin motor KIFC1 is required for tubulin acetylation and actin-dependent spindle migration in mouse oocyte meiosis.

Mammalian oocyte maturation is a unique asymmetric division, which is mainly because of actin-based spindle migration to the cortex. In the present study, we report that a kinesin motor KIFC1, which is associated with microtubules for the maintenance of spindle poles in mitosis, is also involved in actin dynamics in murine oocyte meiosis, co-localizing with microtubules during mouse oocyte maturation. Depletion of KIFC1 caused the failure of polar body extrusion, and we found that meiotic spindle formation and chromosome alignment were disrupted. This might be because of the effects of KIFC1 on HDAC6 and NAT10-based tubulin acetylation, which further affected microtubule stability. Mass spectroscopy analysis revealed that KIFC1 also associated with several actin nucleation factors and we found that KIFC1 was essential for the distribution of actin filaments, which further affected spindle migration. Depletion of KIFC1 leaded to aberrant expression of formin 2 and the ARP2/3 complex, and endoplasmic reticulum distribution was also disturbed. Exogenous KIFC1 mRNA supplement could rescue these defects. Taken together, as well as its roles in tubulin acetylation, our study reported a previously undescribed role of kinesin KIFC1 on the regulation of actin dynamics for spindle migration in mouse oocytes.

Nivalenol affects spindle formation and organelle functions during mouse oocyte maturation.

Oocyte maturation is essential for fertilization and early embryo development, and proper organelle functions guarantee this process to maintain high-quality oocytes. The type B trichothecene nivalenol (NIV) is a mycotoxin produced by Fusarium oxysporum and is commonly found in contaminated food. NIV intake affect growth, the immune system, and the female reproductive system. Here, we investigated NIV toxicity on mouse oocyte quality. Transcriptome analysis results showed that NIV exposure altered the expression of multiple genes involved in spindle formation and organelle function in mouse oocytes, indicating its toxicity on mouse oocyte maturation. Further analysis indicated that NIV exposure disrupted spindle structure and chromosome alignment, possibly through tubulin acetylation. NIV exposure induced aberrant mitochondria distribution and reduced mitochondria number, mitochondria membrane potential (MMP), and ATP levels. In addition, NIV caused the abnormal distribution of the Golgi apparatus and altered the expression of the vesicle trafficking protein Rab11. ER distribution was also disturbed under NIV exposure, indicating the effects of NIV on protein modification and transport in oocytes. Thus, our results demonstrated that NIV exposure affected spindle structure and organelles function in mouse oocytes.

Exposure to nivalenol declines mouse oocyte quality via inducing oxidative stress-related apoptosis and DNA damage†.

Mammalian oocyte quality is critical for fertilization and early embryo development. The type B trichothecene nivalenol (NIV) is a mycotoxin produced by Fusarium oxysporum, and it is commonly found with deoxynivalenol in contaminated food or feed. NIV has been shown to affect the immune system and female reproductive system, cause emesis and growth retardation. Here, we investigated the toxicity of NIV on mouse oocyte quality, as well as the protective effects of melatonin on the NIV-exposed oocytes. We found NIV exposure caused meiotic arrest and further induced the failure of polar body extrusion in mouse oocytes. Transcriptome analysis data showed that NIV exposure altered the expression of multiple pathway-related genes in oocytes, indicating its wide toxicity on oocyte maturation. Based on the RNA-seq data, we showed that NIV exposure induced oxidative stress and caused DNA damage in oocytes. Besides, autophagy, and early apoptosis were also found in NIV-exposed oocytes. Treatment with melatonin significantly ameliorated these defects through its effects on ROS level. Thus, our results demonstrated that exposure to NIV affected oocyte quality and melatonin treatment could reduce the defects caused by NIV in mouse oocytes.

DEHP exposure to lactating mice affects ovarian hormone production and antral follicle development of offspring.

Di (2-ethylhexyl) phthalate (DEHP) is widely used as a plastic additive and it could induce reproduction defects and fertility in mammals as environmental endocrine disruptor. However, the effects and potential mechanism of DEHP exposure during lactation stage on follicular development of offspring are still unclear. In this study, we found that the total primordial follicle number and antral follicles in the suckling of mice exposed to DEHP during lactation was significantly reduced. RNA-seq analysis results showed that the transcription levels of genes related to steroid production, ovarian hormone secretion and oxidative stress were significantly changed, which led to a decrease in 17ß-estradiol and an increase in oxidative stress. The proportion of DNA damage marker γH2AX in the ovary of female suckling exposed to DEHP was significantly increased. We also found an increase in the level of ovarian apoptosis, and the proliferation of ovarian granulosa cells was inhibited. These alterations also lead to abnormal spindle and chromosome misalignment during oocyte maturation. Overall, our data indicate that lactation exposure to DEHP can affect the secretion of hormones and the development of antral follicles in suckling mice by affecting the secretion pathways of ovarian hormone enzymes and oxidative stress pathway.

Melatonin reverses mitochondria dysfunction and oxidative stress-induced apoptosis of Sudan I-exposed mouse oocytes.

Sudan I is one of the industry dyes and widely used in cosmetics, wax agent, solvent and textile. Sudan I has multiple toxicity such as carcinogenicity, mutagenicity, genotoxicity and oxidative damage. However, Sudan I has been illegally used as colorant in food products, triggering worldwide attention about food safety. Nevertheless, the toxicity of Sudan I on reproduction, particularly on oocyte maturation is still unclear. In the present study, using mouse in vivo models, we report the toxicity effects of Sudan I on mouse oocyte. The results reflect that Sudan I exposure disrupts spindle organization and chromosomes alignment as well as cortical actin distribution, thus leading to the failure of polar body extrusion. Based on the transcriptome results, it is found that the exposure of Sudan I leads to the change in expression of 764 genes. Moreover, it's further reflected that the damaging effects of Sudan I are mediated by the destruction of mitochondrial functions, which induces the accumulated ROS to stimulate oxidative stress-induced apoptosis. As an endogenous hormone, melatonin within the ovarian follicle plays function on improving oocyte quality and female reproduction by efficiently suppressing oxidative stress. Moreover, melatonin supplementation also improves oocyte quality and increases fertilization rate during in vitro culture. Consistent with these, we find that in vivo supplementation of melatonin efficaciously suppresses mitochondrial dysfunction and the accompanying apoptosis, thus reverses oocyte meiotic deteriorations. Collectively, our results prove the reproduction toxicity of Sudan I for the exposure of Sudan I reduces the oocyte quality, and demonstrate the protective effects of melatonin against Sudan I-induced meiotic deteriorations.

Increased Environment-Related Metabolism and Genetic Expression in the In Vitro Matured Mouse Oocytes by Transcriptome Analysis.

Infertility in humans at their reproductive age is a world-wide problem. Oocyte in vitro maturation (IVM) is generally used in such cases to acquire the embryo in assisted reproductive technology (ART). However, the differences between an in vivo (IVO) and IVM culture environment in the RNA expression profile in oocytes, remains unclear. In this study, we compared the global RNA transcription pattern of oocytes from in vitro and in vivo maturation. Our results showed that 1,864 genes differentially expressed between the IVO and IVM oocytes. Among these, 1,638 genes were up-regulated, and 226 genes were down-regulated, and these changes were mainly divided into environmental adaption, metabolism, and genetic expression. Our detailed analysis showed that the expression of genes that belonged to metabolism-related processes such as energy metabolism, nucleotide metabolism, and carbohydrate metabolism was changed; and these genes also belonged to organismal systems including environmental adaptation and the circulatory system; moreover, we also found that the relative gene expression of genetic expression processes, such as protein synthesis, modification, and DNA replication and repair were also altered. In conclusion, our data suggests that in vitro maturation of mouse oocyte resulted in metabolism and genetic expression changes due to environmental changes compared with in vivo matured oocytes.

The Ameliorating Effects of Bushen Huatan Granules and Kunling Wan on Polycystic Ovary Syndrome Induced by Dehydroepiandrosterone in Rats.

AIM: To investigate the effects of Bushen Huatan Granules (BHG) and Kunling Wan (KW), the two Chinese medicines, on the regulation of polycystic ovary syndrome (PCOS) and their underlying mechanisms. MATERIALS AND METHODS: PCOS rat model was established by subcutaneous injection of dehydroepiandrosterone (DHEA) (6 mg/100 g/day) for 20 days, followed by treatment with BHG (0.75, 1.49, and 2.99 g/kg) or KW (0.46, 0.91, and 1.82 g/kg) by gavage for 4 weeks. Estrous cycle was detected by vaginal smears. Follicles development was assessed by histology. Levels of testosterone and insulin in serum were tested by ELISA. Apoptosis of Granulosa cells (GCs) was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling staining. Pathways associated with apoptosis were detected with western blot. Pregnancy outcome was also assessed. GCs were pre-treated with 10-5 M testosterone in vitro for 24 h, then incubated with serum from rats receiving BHG (1.49 g/kg) or KW (1.82 g/kg). The parameters concerning apoptosis, mitochondrial function and endoplasmic reticulum stress were assessed. RESULTS: Post-treatment with either BHG or KW ameliorated DHEA-induced irregular estrous cycles, follicles development abnormalities, increase of testosterone and insulin in serum, and the apoptosis of GCs. Post-treatment with BHG decreased the expression of cleaved caspase-9/caspase 9, release of cytochrome C from mitochondria, and mitochondria reactive oxygen species production, increased activities of complex I, II, IV of ovarian tissue. Post-treatment with KW decreased the levels of caspase-12, GRP78, C/EBP homologous protein, phosphorylation of IRE-I, x-box-binding protein 1s, as well as phosphorylation of proline-rich receptor-like protein kinase, phosphorylation of eukaryotic translation initiation factor 2α and ATF4 of ovarian tissue and GCs. Both BHG and KW ameliorated pregnancy outcome. CONCLUSION: This study demonstrated BHG or KW as a potential strategy for treatment of PCOS induced by DHEA, and suggested that the beneficial role of the two medicines were mediated by different pathway with the effect of BHG being correlated with the regulation of mitochondria, while the effect of KW being attributable to protection of endoplasmic reticulum stress.

Efficacy of acupuncture for sciatica: study protocol for a randomized controlled pilot trial.

BACKGROUND: Acupuncture is widely used for pain diseases while evidence of its efficacy for sciatica is insufficient. We aim to explore the feasibility and efficacy of acupuncture with different acupoint selecting strategies for sciatica induced by lumbar disc herniation. METHODS: This is a multicenter, three-arm, patient-assessor-blinded randomized controlled pilot trial. Ninety patients will be assigned randomly into 3 groups including disease-affected meridians (DAM) group, non-affected meridians (NAM) group, and sham acupuncture (SA) group in a 1:1:1 ratio. The trial involves a 4-week treatment along with follow-up for 22 weeks. The primary outcome is the change of leg pain intensity measured by the visual analogue scale (VAS) from baseline to week 4 after randomization. Secondary outcomes include functional status, back pain intensity, and quality of life. Adverse events will also be recorded. DISCUSSION: The results will inspire the optimal acupuncture strategy for sciatica and help establish a better design as well as power calculation for a full-scale study. TRIAL REGISTRATION: ChiCTR2000030680 (Chinese Clinical Trial Registry, http://www.chictr.org.cn , registered on 9 March 2020).

Transgenerational Inheritance of Reproductive and Metabolic Phenotypes in PCOS Rats.

Androgen exposure of female fetuses could be an important factor in the development of polycystic ovary syndrome (PCOS) in subsequent generations. The present study aimed to investigate the transgenerational effects of PCOS on the growth, reproduction, and metabolism of the first- and second-generation offspring in rats. Female F0 rats received excessive dehydroepiandrosterone (DHEA) exposure to establish PCOS or the same amount of vehicle as controls. These F0 females were crossed with normal males to obtain control (C) and DHEA (D) F1 offspring, whereas F2 offspring were obtained by inter-crossing between F1 rats for 4 groups: (1) C♂-C♀; (2) D♂-C♀; (3) C♂-D♀ and (4) D♂-D♀. Compared with control groups, F1 and F2 offspring with ancestral DHEA exposure showed higher body weight with increasing age. In addition, female F1 and F2 offspring with ancestral DHEA exposure exhibited PCOS-like reproductive and metabolic phenotypes, including disrupted estrous cycles and polycystic ovaries, as well as increased serum levels of testosterone, impaired glucose tolerance and widespread metabolic abnormalities. Male offspring with ancestral DHEA exposure exhibited lower quality of sperms. These findings confirm the negative effects of excessive androgen exposure of female fetuses on subsequent generations.