Human amnion-derived mesenchymal stem cells improve subclinical hypothyroidism by immunocompetence mediating apoptosis inhibition on thyroid cells in aged mice.

Subclinical hypothyroidism (SCH) affects 10% of the global population, which is most prevalent in women and the elderly. However, it remains debatable whether the elderly with subclinical hypothyroidism needs thyroxine supplement. Human amnion-derived mesenchymal stem cells (hAMSCs) could play important roles in autoimmune diseases, suggesting that hAMSC be a candidate to regulate the thyroid function of female age-related subclinical hypothyroidism. Herein, we established the model of SCH in the aged female mice. This study was designed to investigate whether human amnion-derived mesenchymal stem cells (hAMSC) could effect on immune regulation, apoptosis inhibition of thyroid cells, thyroid function, blood lipid levels, and heart function. In addition, qualified hAMSCs were intravenously injected into aged female SCH mice via the tail vein on day 0 and day 10. The levels of thyroid hormone and blood lipids as well as cardiac function, serum immunological indexes, and apoptosis of thyroid cells were then analyzed on day 5, 10, 15, and 20; meanwhile, the quantity of Th1, Th2, Th17, and Treg immune cells in peripheral blood was evaluated before and on day 20 post-injection. Our study demonstrated that after hAMSC transplantation, the thyroid functions, blood lipid levels, and heart function indexes of age-related SCH (AR-SCH) mice were significantly improved. Consistent with this, Th1 and Treg cells increased significantly, while Th2 and Th17 cells decreased in peripheral blood. Apoptosis was also suppressed in the thyroid cells. In summary, hAMSC delivery can potentially be a safe and effective therapy for treating SCH in the elderly, improving related complications by immunomodulatory and apoptosis inhibition.

Activating HfX2 (X = S, Se and Te) for the hydrogen evolution reaction by introducing defects: a first-principles study.

An ideal catalyst should have a relative hydrogen adsorption Gibbs free energy (ΔGH) close to zero [J. K. Nørskov, et al., J. Electrochem. Soc., 2005, 152, J23]. However, most of the known catalysts cannot reach this standard. Based on first-principles calculations, we studied the hydrogen evolution reaction (HER) catalytic performance of pristine and defect (including vacancy and heteroatom doping) structures in terms of its ΔGH. We found that the ΔGH values of Co-doped HfS2 and P-doped HfSe2 are extremely close to zero, even closer than that of Pt (111), indicating that they are excellent catalysts. Moreover, we found that the source of the HER catalytic performance of Co-doped HfS2 is the reduction of electron accumulation of the active site S atom. Our work provides two potential ideal catalysts and provides guidance for the experimental group to search for suitable catalysts.

Intrinsic type-II van der Waals heterostructures based on graphdiyne and XSSe (X = Mo, W): a first-principles study.

Typical transition-metal dichalcogenides (TMDs) and graphdiyne (GDY) often form type-I heterojunctions, which will limit their applications in optoelectronic devices. Here, type-II heterojunctions based on GDY and TMDs are constructed by introducing Janus structures. An intrinsic type-II heterojunction is presented when the GDY is in contact with a Se-terminated layer, but a type-I heterojunction would appear when it is in contact with the S-terminated surface. Such a difference in band alignment can be attributed to the interaction between the dipole moment formed by the Janus structure and the graphdiyne layer. Furthermore, for heterojunctions in contact with the S-terminated layer, they can be converted into type-II heterojunctions by a small external electric field (for WSSe, only 0.05 V A-1 is required). This approach can suggest a convenient design strategy for the application of graphdiyne in a wider range of applications.

Macrophage membrane-coated nanoparticles for the treatment of infectious diseases.

Infectious diseases severely threaten human health, and traditional treatment techniques face multiple limitations. As an important component of immune cells, macrophages display unique biological properties, such as biocompatibility, immunocompatibility, targeting specificity, and immunoregulatory activity, and play a critical role in protecting the body against infections. The macrophage membrane-coated nanoparticles not only maintain the functions of the inner nanoparticles but also inherit the characteristics of macrophages, making them excellent tools for improving drug delivery and therapeutic implications in infectious diseases (IDs). In this review, we describe the characteristics and functions of macrophage membrane-coated nanoparticles and their advantages and challenges in ID therapy. We first summarize the pathological features of IDs, providing insight into how to fight them. Next, we focus on the classification, characteristics, and preparation of macrophage membrane-coated nanoparticles. Finally, we comprehensively describe the progress of macrophage membrane-coated nanoparticles in combating IDs, including drug delivery, inhibition and killing of pathogens, and immune modulation. At the end of this review, a look forward to the challenges of this aspect is presented.

Effect and mechanism of Hashimoto thyroiditis on female infertility: A clinical trial, bioinformatics analysis, and experiments-based study.

Diagnosing Hashimoto thyroiditis (HT) relies on thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) titers. The influence of these antibodies on female infertility remains a subject of debate. This study aims to explore the effect and mechanism of HT on female infertility. First, a single-center cross-sectional study was conducted to investigate whether TgAb and TPOAb are the key factors leading to female infertility. Second, bioinformatic analysis was performed to investigate the potential target molecules and pathways. Third, in vivo experiments were performed to explore the effects of elevated TgAb levels on embryo implantation in a mouse model of autoimmune thyroiditis (AIT). Four hundred and five infertile women and 155 healthy controls were enrolled in the cross-sectional study. Results indicated that the TPOAb titer was associated with female infertility, while the TgAb titer showed no significant association. The increased levels of TgAb and TPOAb are not significantly correlated with anti-Mullerian hormone. Bioinformatic analysis indicated that the common target molecules for HT and female infertility include interleukin (IL)-6, IL-10, matrix metalloproteinase 9, and tumor necrosis factor, suggesting potential regulation through multiple signaling pathways such as HIF-1, VEGF, MAPK, and Th17 cell differentiation. A certain dose of porcine thyroglobulin can successfully establish a mouse model of AIT. In this mouse model, embryo implantation and ovarian reserve remain unaffected by elevated TgAb levels. In conclusion, the serum TPOAb titer was associated with infertility due to female factors but the TgAb titer showed no significant association. A simple increase in serum TgAb titer does not affect embryo implantation and ovarian reserve in the AIT model.

Cell-Based Biomaterials for Coronavirus Disease 2019 Prevention and Therapy.

Coronavirus disease 2019 (COVID-19) continues to threaten human health, economic development, and national security. Although many vaccines and drugs have been explored to fight against the major pandemic, their efficacy and safety still need to be improved. Cell-based biomaterials, especially living cells, extracellular vesicles, and cell membranes, offer great potential in preventing and treating COVID-19 owing to their versatility and unique biological functions. In this review, the characteristics and functions of cell-based biomaterials and their biological applications in COVID-19 prevention and therapy are described. First the pathological features of COVID-19 are summarized, providing enlightenment on how to fight against COVID-19. Next, the classification, organization structure, characteristics, and functions of cell-based biomaterials are focused on. Finally, the progress of cell-based biomaterials in overcoming COVID-19 in different aspects, including the prevention of viral infection, inhibition of viral proliferation, anti-inflammation, tissue repair, and alleviation of lymphopenia are comprehensively described. At the end of this review, a look forward to the challenges of this aspect is presented.

Establishing a human embryonic stem cell line (SKLRMe005-A) from a blastocyst with congenital heart disease (CHD).

GATA binding protein 6 (GATA6) is an important transcription factor of cardiovascular endothelial cells, has the potential to regulate the process of cardiac development. Consequently, its abnormal expression is related to congenital heart disease.Human GATA6 gene clones were on chromosome 18 q11.1- q 11.2, consists of 7 exons and 6 intron.Now, a human embryonic stem cell line with GATA6 c.620_647del (p.S208Afs*77) mutation was generated. Interestingly, the ESC line displayed a normal karyotype, pluripotency and morphology of stem cells.This cell line has the ability to undergo differentiation into three germ layers in vivo.

The effect of a traditional Chinese quadri-combination therapy and its component quercetin on recurrent spontaneous abortion: A clinical trial, network pharmacology and experiments-based study.

Objective: To explore the effect and mechanisms of a traditional Chinese quadri-combination therapy [Bushen, Yiqi, Lixue and Yangtai (BYLY)] in treating recurrent spontaneous abortion (RSA). Methods: A clinical trial was conducted to study the effect of BYLY on RSA. Pharmacological network analysis and UPLC-Q/TOF-mass spectrometry (MS) were applied to investigate the key active component in BYLY and potential targets. Cellular experiments based on former results were performed to examine the mechanism of BYLY in the treatment of RSA. Results: Four hundred and eighty participants enrolled in the clinical trial. The results showed that, compared with the use of BYLY or duphaston alone, a combination of duphaston and BYLY could decrease the early abortion rate in RSA (p < 0.001). Network pharmacological analysis indicated that BYLY contained 132 active components and 146 core targets, and the quercetin maybe the key effective component. In vitro experiments found that pretreatment of quercetin at the correct concentration (2 µM) prevented hypoxia-induced viability and proliferation reduction, and apoptosis and mitochondrial dysfunction. Furthermore, quercetin could modulate mitochondrial fission/fusion balance in trophoblasts, and specifically decrease the expression of Drp1 by regulating miR-34a-5p. Conclusion: BYLY could improve pregnancy outcomes of RSA, based on multi-components and multi-targets. The protective effect of quercetin on trophoblasts, through decreasing Drp1 expression via regulating miR-34a-5p, might be one possible effective mechanism.

Effect of dehydroepiandrosterone on atherosclerosis in postmenopausal women.

In China, cardiovascular disease (CVD) has surpassed malignant tumours to become the disease with the highest mortality rate, and atherosclerosis (AS) is an important pathological cause of CVD. Dehydroepiandrosterone (DHEA) is the most abundant steroid hormone in circulating human blood and is a precursor of estrogen and androgen. DHEA is converted into a series of sex hormones in local peripheral tissues where its acts physiologically. DHEA also acts therapeutically, thereby avoiding the adverse systemic reactions to sex hormones. DHEA inhibits AS, thus inhibiting the development of CVD, and it improves the prognosis for CVD. The incidence of CVD in postmenopausal women is substantially higher than that in premenopausal women, and that incidence is believed to be related to a decrease in ovarian function. The current review analyzes the mechanisms of postmenopausal women's susceptibility to AS. They tend to have dyslipidemia, and their vascular smooth muscle cells (VSMCs) proliferate and migrate more. In addition, oxidative stress and the inflammatory response of endothelial cells (ECs) are more serious in postmenopausal women. This review also discusses how DHEA combats AS by countering these mechanisms, which include regulating the blood lipid status, protecting ECs (including coping with oxidative stress and inflammatory reactions of the vascular endothelium, inhibiting apoptosis of ECs, and inducing NO production) and inhibiting the proliferation and migration of VSMCs. As a result, DHEA has great value in preventing AS and inhibiting its progression in postmenopausal women.

Establishment of human embryonic stem cell (SKLRMe001-A)carrying Azoospermic factor c (AZFc) deletions.

The absence of azoospermia factor c (AZFc) is a common molecular cause of sperm failure. In men with non-obstructive azoospermia or severe oligospermia, the incidence of AZFc is around 10%. The AZFc region is located at the far end of the Yqll chromosome which has three non-overlapping sub-regions with a high frequency of deletion. Now, we generated a human embryonic stem cell line (SKLRMe001-A) that carries a deleted AZFc gene on the Y chromosome. The ESC line maintains a stem cell-like morphology, pluripotency, and has a normal karyotype. The cells can also differentiate into all three germ layers in vivo.

A Novel Long Noncoding RNA, Lnc-OAD, Is Required for Bone Morphogenetic Protein 2- (BMP-2-) Induced Osteoblast Differentiation.

Long noncoding RNAs (lncRNAs) play very important roles in cell differentiation. Our recent study has demonstrated that a novel lncRNA named lnc-OAD modulated 3T3-L1 adipocyte differentiation. In the present study, we examined the roles of lnc-OAD in bone morphogenetic protein 2- (BMP-2-) induced osteoblast differentiation. Lnc-OAD expression was increased during BMP-2-induced osteoblast differentiation in C3H10T1/2 mesenchymal stem cells and MC3T3-E1 preosteoblast cells. Knockdown of lnc-OAD expression by specific siRNA remarkably decreased early osteoblast differentiation. In addition, stable knockdown of lnc-OAD by lentivirus vector also significantly inhibited late osteoblast differentiation and matrix mineralization in vitro. Conversely, stably overexpressed lnc-OAD with lentiviral vector accelerated osteoblast differentiation. Mechanistically, knockdown of lnc-OAD reduced significantly the phosphorylation of AKT and the expression of Osterix induced by BMP-2, while overexpression of lnc-OAD enhanced the phosphorylation of AKT and the expression of Osterix. Taken together, our study suggests that lnc-OAD plays an important role in modulating BMP-2-induced osteoblast differentiation via, at least in part, regulating the AKT-Osterix signaling axis.

Variations in the Antithyroid Antibody Titre During Pregnancy and After Delivery.

BACKGROUND: Immunosuppression occurs during pregnancy, and the antithyroid antibody titre drops, rebounding after delivery. We aimed to determine variations in antithyroid antibody titres during pregnancy and after delivery. METHODS: This retrospective study was conducted in a single centre. Antibody titres of 142 patients were measured to assess variations in the levels of thyroid-stimulating hormone receptor antibodies (TRAbs), thyroid peroxidase antibodies (TPOAbs), and thyroid globulin antibodies (TgAbs). We compared the titres of each antibody between adjacent time periods (eg, first trimester (T1) vs second trimester (T2), T2 vs third trimester (T3), T3 vs the postpartum period (PP)) by paired t-test or the Wilcoxon test. Then, we analysed data from patients with complete laboratory examination results in all four periods with the Friedman test, performing comparisons among groups. RESULTS: In the TgAb group, significant differences existed between T1 and T2 and between T2 and T3 in the LT4 subgroup and between T1 and T2 in the no-medication subgroup. In the TRAb group, significant differences existed between T1 and T2 in the LT4 subgroup. In the TPOAb group, significant differences existed among each group in the LT4 subgroup, and there were significant differences between T1 and T2 and between T2 and T3 in the no-medication subgroup. The Friedman test showed that the P-values were 0.013 and 0.004 in the LT4 and no-medication subgroups of the TgAb group, respectively; 0.122 in the LT4 subgroup of the TRAb group; and <0.001 and 0.272 in the LT4 and no-medication subgroups of the TPOAb group, respectively. In the LT4 subgroup of the TgAb group, the P-values for comparisons of time periods were 0.602 between T1 and T2, 0.602 between T2 and T3, 0.006 between T1 and T3, and 0.602 between T3 and PP. In the no-medication subgroup of the TgAb group, the P-values were 0.078 between T1 and T2, 1.000 between T2 and T3, 0.011 between T1 and T3, and 0.078 between T3 and PP. In the LT4 subgroup of the TPOAb group, the P-values were 0.09 between T1 and T2, 0.014 between T2 and T3, <0.001 between T1 and T3, and 0.772 between T3 and PP. CONCLUSION: We can conclude that the TgAb and TPOAb titres dropped during pregnancy.

Alterations in the intestinal microbiome associated with PCOS affect the clinical phenotype.

Polycystic ovarian syndrome (PCOS), characterized by chronic anovulation and hyperandrogenaemia, is a complex endocrine and metabolic disorder commonly seen in women of reproductive age. Multiple factors, including the intestinal microbiome, affect the pathogenesis and development of PCOS. However, the specific mechanisms by which gut microbes play a role in PCOS remain elusive. This review summarizes recent research about the transformational changes in gut microbes revealed in PCOS patients and the possible mechanisms and pathways by which the intestinal microbiome exerts influence on PCOS progression and phenotypes. In addition to the intestinal microbiome, evidence from animal studies suggests changes in the vaginal microbiome under PCOS conditions. The alteration of microbiome could affect oestrus cycle and PCOS phenotypes. Microbiome is closely associated with medicine and therapeutic approaches. Microbiome influences drug and therapy response and itself is a new source of therapy. Accurate modulation of the intestinal and vaginal microbiome is a potential therapy for PCOS patients. Future studies are required to elucidate the specific role of each particular genera of microbiota and the mechanism by which microbiome impacts the pathogenesis, progression and phenotypes of PCOS.

Downregulation of hsa_circRNA_0001400 Helps to Promote Cell Apoptosis Through Disruption of the circRNA_0001400-miR-326 Sponge in Cervical Cancer Cells.

Background: In recent years, circular RNAs (circRNAs) have been reported to serve as essential regulators in several human cancers. Nevertheless, the function and mechanism of circRNAs in cervical cancer remain elusive. Methods: Flow cytometry assays were performed to measure cell apoptosis and cell cycle. Colony Formation and transwell chamber were performed to measure cell migration and invasion. Double luciferase reporter for gene analysis was used to detect the interaction between hsa-circRNA_0001400, miR-326, and Akt. Relative protein levels were determined by immunoblotting and relative gene levels were determined by quantitative real-time PCR. Tumor Xenograft Modeling was used to evaluate the effect of hsa_circRNA_0001400_siRNA in vivo. Results: In the present study, we showed that hsa_circRNA_0001400 was highly expressed in cervical cancer tissues relative to in matched normal tissue. We found that hsa_circRNA_0001400_siRNA significantly promoted the apoptosis of cervical cancer cells and arrested the cell cycle and migration of cervical cancer cells. We showed that hsa_circRNA_0001400_siRNA can inhibit the protein expression of Akt and that the inhibition of miR-326 could rescue the inhibition of Akt in cervical cancer cells. We found that has-miR-326 was downregulated in cervical cancer tissues and hsa_circRNA_0001400_siRNA could increase the gene expression of has-miR-326. We also observed that hsa_circRNA_0001400_siRNA inhibited the growth and angiogenesis of SiHa xenografts in nude mice. Conclusion: In conclusion, this study provides evidence that the hsa_circRNA_0001400-miR-326-Akt network promotes cervical cancer progression. Notably, our findings demonstrate the novel antitumor effects of hsa_circRNA_0001400_siRNA in cervical cancer.

Human amnion-derived mesenchymal stem cells improved the reproductive function of age-related diminished ovarian reserve in mice through Ampk/FoxO3a signaling pathway.

BACKGROUND: Age-related diminished ovarian reserve (AR-DOR) reduced the quality of oocytes, resulting in decreased female fertility. Aging is tightly related to abnormal distribution and function of mitochondria, while mitophagy is a major process to maintain normal quality and quantity of mitochondria in cells, especially in oocytes which containing a large number of mitochondria to meet the demand of energy production during oocyte maturation and subsequent embryonic development. Ampk/FoxO3a signaling is crucial in the regulation of mitophagy. It is reported mesenchymal stem cells (MSCs) can improve ovarian function. Here we aim to explore if human amnion-derived mesenchymal stem cells (hAMSCs) are effective in improving ovarian function in AR-DOR mice and whether Ampk/FoxO3a signaling is involved. METHODS: The AR-DOR model mice were established by 32-week-old mice with 3-8 litters, significantly low serum sex hormone levels and follicle counts. The old mice were divided into 5 treatment groups: normal saline (NS, control), 1% human serum albumin (HSA, resolver), low dose (LD, 5.0 × 106cells/kg), middle dose (MD, 7.5 × 106cells/kg), and high dose (HD, 10.0 × 106cells/kg). The prepared hAMSCs were injected through tail vein. Serum sex hormone level, follicle counts, fertilization rate, gestation rate, little size, apoptosis of granulosa and stromal cells, expression level of Sod2, Ampk, and ratio of phosphorylated FoxO3a to total FoxO3a in ovaries were examined. RESULTS: Our results show that after hAMSC transplantation, the ovarian function in AR-DOR mice was significantly improved, meanwhile the apoptosis of granulosa and stromal cells in the ovaries was significantly repressed, the expression level of Ampk and the ratio of phosphorylated FoxO3a to total FoxO3a both were significantly increased, meanwhile increased Sod2 expression was also observed. CONCLUSION: Our results demonstrate hAMSC transplantation via tail-injection can improve ovarian function of AR-DOR mice through Ampk/FoxO3a signaling pathway.

The novel role of Hippo-YAP/TAZ in immunity at the mammalian maternal-fetal interface: Opportunities, challenges.

The Hippo-Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ), originally identified as a regulator of tissue generation and tumorigenesis, has been proven to have a pivotal position in immunity. Its multi-faceted roles in regulating immunity cover both intrinsic mechanism of immune cells and the crosstalk with non-immune cells. Survival of the allogeneic embryo in the maternal uterine environment depends on immune tolerance, supported by the highly orchestrated cooperation between decidual immune cells, decidual stromal cells and trophoblasts at the maternal-fetal interface. The abnormal maternal-fetal dialogue is believed to be associated with adverse pregnancy outcomes such as spontaneous pregnancy loss. Recent breakthroughs shed light on the how the Hippo-YAP/TAZ manipulate the decidualization and trophoblast invasion, while further research is needed to integrate and reconcile existing findings of the Hippo-YAP/TAZ in immunity and to extend them at the context of pregnancy. In this review, we summarized the Hippo-YAP/TAZ pathways, detailed the effects of YAP/TAZ on immune cells, and discussed the role of YAP/TAZ at the maternal-fetal interface and the potential of YAP/TAZ on immunity regulation at the context of pregnancy. Given the remarkable effect of therapeutic intervention of YAP/TAZ in cancer and autoimmune diseases, it is worthy to explore the response to YAP/TAZ inhibition in the maternal-fetal immunity. This may provide a new valuable target for therapy of pregnancy loss, or potentially other pregnancy complications.

The Clinical Value and Variation of Antithyroid Antibodies during Pregnancy.

Antithyroid antibodies, which include thyroid-stimulating hormone receptor antibodies (TRAbs), thyroid peroxidase antibodies (TPOAbs), and thyroid globulin antibodies (TgAbs), are widely known for their tight association with thyroid autoimmune diseases. The variation in all three kinds of antibodies also showed different trends during and after pregnancy (Weetman, 2010). This article reviewed the the physiological changes, while focusing on the variation of thyroid antibodies concentration in women during and after pregnancy, and adverse consequences related to their elevation. Since abnormal elevations of these antithyroid antibodies may lead to adverse outcomes in both mothers and fetuses, special attention must be paid to the titer of the antibodies during pregnancy. The molecular mechanisms of the variations in those antibodies have yet to be explained. The frequency and timing of thyroid antibody measurement, as well as different reference levels, also remain to be elucidated.

Chinese herbal medicine for acute upper respiratory tract infections and reproductive safety: A systematic review.

Acute upper respiratory tract infections (AURTIs) are common and self-limited in people with normal immunity but sometimes lead to poor clinical outcomes under specific conditions such as pregnancy if not treated appropriately. Chinese herbal medicines (CHM), which are widely used to treat AURTIs, have proven to be effective in preclinical and clinical studies. This review focuses on the bioactivities of typical CHM and the adverse reactions they cause, and especially issues with reproductive safety when treating AURTIs. The main mechanisms for clinical efficacy may include anti-viral, anti-bacterial, anti-inflammatory, antipyretic, and immunomodulatory action as indicated by preclinical evidence. Most clinical trials indicate that CHM shortens the natural course of AURTIs and that it relieves related symptoms such as a fever, headaches, coughing, myalgia, a cold, sore throat, and a nasal obstruction. However, some CHM have a range of adverse effects and potentially affect reproduction from endocrinal secretion to embryo development while others do not. Therefore, clinical adverse reactions and preclinical studies on the toxicity of CHM are discussed. More reliable evidence is required to conclude that CHM are efficacious and safe for pregnant women with AURTIs. This review should help to promote advances in the research on and development of CHM as alternative treatments for AURTIs and offer insight into strategies to manage the safety of CHM during clinical use.

New thoughts in exploring the pathogenesis, diagnosis, and treatment of threatened abortion.

Threatened abortion is a common complication of pregnancy. Since the underlying mechanisms behind this condition are complicated, predicting and treating threatened abortion is a challenge for clinicians. Interestingly, a recent article in Bioscience Trends (Biosci Trends 2019; DOI: 10.5582/bst.2019.01111) revealed a higher, not lower, level of ꞵ-human chorionic gonadotropin (hCG) and estrogen during the first 6 weeks of pregnancy, suggesting a novel association between ꞵ-hCG, estrogen, and threatened abortion. Unfortunately, this study was limited by its small sample size, unconvincing trial design, and inadequate exploration of the underlying mechanisms. This low-quality evidence indicates that a higher level of ꞵ- hCG and estrogen is associated with threatened abortion. However, that work provided some new insights for further studies of threatened abortion.

Sperm DNA fragmentation valued by SCSA and its correlation with conventional sperm parameters in male partner of recurrent spontaneous abortion couple.

The objective of this study is to evaluate the predictive value of sperm DNA fragmentation Index (DFI) in unexplained recurrent spontaneous abortion (RSA) and to investigate its correlation with conventional sperm parameters. Besides, we aimed to reveal the necessity of establishing a DFI clinical threshold of each laboratory for the prognostic diagnosis of RSA and establish our own DFI threshold. Semen samples were collected from male partners of RSA patients (n = 139) and healthy recent fathers (control, n = 200). DFI was tested using SCSA and conventional semen analysis was performed using an automatic semen analyzer. The DFI value and distribution were compared between the two groups using corresponding statistical software. The diagnostic threshold value was established by ROC curve. The correlation between DFI and the conventional semen parameters of the 139 cases was further analyzed using Student's t test and Mann-Whitney U test. Our result showed that DFI was significantly higher in RSA patients compared with normal donor controls. We established our own DFI threshold at 13.59%. There was only a weak partial correlation between DFI values and conventional sperm analysis parameters. Our present study suggested that DFI might be used as a valuable predictor for RSA independent of conventional sperm parameters. Additionally, we recommend that each laboratory should establish its own clinical DFI threshold for more precise prediction of RSA and we recommend that sperm DNA fragmentation test should be included in complete sperm quality assessment in addition to conventional semen analysis for RSA male partners.