Meta-analysis of Clinical Efficacy of Aspirin and Low Molecular Weight Heparin in the Treatment of Recurrent Spontaneous Abortion.

Objective: To investigate the clinical effect of aspirin (ASA) combined with low molecular weight heparin (LMWH) in the treatment of recurrent spontaneous abortion (RSA). Methods: PubMed, Cochrane, Wanfang, CNKI, and other databases were searched to collect randomized controlled trials (RCT) of aspirin combined with LMWH in the treatment of RSA from the establishment of the database to July 31, 2023. The literature was screened, and the information was extracted according to the pre-established criteria. The Reviews Manager 5.4 software was used for data analysis. Results: A total of 10 RCTs containing 1865 patients with RSA were included in this study. Meta-analysis showed that the regimen of aspirin combined with LMWH treatment significantly increased the neonatal birth rate (P < .01); and the occurrence of preeclampsia was significantly reduced when compared with regimens such as aspirin alone (P = .02); there were no significant differences between the two groups in the incidence of preterm birth (P = .21), neonatal birth weight (P = .38), the incidence of a small amount of patient hemorrhage (P = .41) and fetal growth restriction (P = .93). Conclusion: The combination of aspirin and LMWH offers a clinically significant improvement in live birth rates and reduction in preeclampsia for RSA patients, suggesting a beneficial strategy for clinical practice and future research directions.

Association of maternal risk factors with fetal aneuploidy and the accuracy of prenatal aneuploidy screening: a correlation analysis based on 12,186 karyotype reports.

BACKGROUND: NIPT is becoming increasingly important as its use becomes more widespread in China. More details are urgently needed on the correlation between maternal risk factors and fetal aneuploidy, and how these factors affect the accuracy of prenatal aneuploidy screening. METHODS: Information on the pregnant women was collected, including maternal age, gestational age, specific medical history and results of prenatal aneuploidy screening. Additionally, the OR, validity and predictive value were also calculated. RESULTS: A total of 12,186 analysable karyotype reports were collected with 372 (3.05%) fetal aneuploidies, including 161 (1.32%) T21, 81 (0.66%) T18, 41 (0.34%) T13 and 89 (0.73%) SCAs. The OR was highest for maternal age less than 20 years (6.65), followed by over 40 years (3.59) and 35-39 years (2.48). T13 (16.95) and T18 (9.40) were more frequent in the over-40 group (P < 0.01); T13 (3.62/5.76) and SCAs (2.49/3.95) in the 35-39 group (P < 0.01). Cases with a history of fetal malformation had the highest OR (35.94), followed by RSA (13.08): the former was more likely to have T13 (50.65) (P < 0.01) and the latter more likely to have T18 (20.50) (P < 0.01). The sensitivity of primary screening was 73.24% and the NPV was 98.23%. The TPR for NIPT was 100.00% and the respective PPVs for T21, T18, T13 and SCAs were 89.92, 69.77, 53.49 and 43.24%, respectively. The accuracy of NIPT increased with increasing gestational age (0.81). In contrast, the accuracy of NIPT decreased with maternal age (1.12) and IVF-ET history (4.15). CONCLUSIONS: ①Pregnant patients with maternal age below 20 years had higher risk of aneuploidy, especially in T13; ②A history of fetal malformations is more risky than RSA, with the former more likely to have T13 and the latter more likely to have T18; ③Primary screening essentially achieves the goal of identifying a normal karyotype, and NIPT can accurately screen for fetal aneuploidy; ④A number of maternal risk factors may influence the accuracy of NIPT diagnosis, including older age, premature testing, or a history of IVF-ET. In conclusion, this study provides a reliable theoretical basis for optimizing prenatal aneuploidy screening strategies and improving population quality.

Altered local RAS in the liver increased the risk of NAFLD in male mouse offspring produced by in vitro fertilization.

BACKGROUND: Assisted reproductive technology (ART) is associated with an increased risk of adverse metabolic health in offspring, and these findings have been demonstrated in animal models without parental infertility issues. However, it is unclear what changes lead to abnormal metabolism. The activation of the renin-angiotensin system (RAS) has been related to various aspects of metabolic syndrome. Thus, we focused on the local RAS of the liver, which is the central organ for glucose and lipid metabolism in offspring conceived by in vitro fertilization (IVF), and studied the role of local liver RAS in metabolic diseases. METHODS: Male C57BL/6 mouse offspring obtained by natural pregnancy and IVF were fed a standard chow diet or a high-fat diet (HFD) from 4 weeks of age through 16 weeks of age. We assessed glucose and lipid metabolism, hepatic histopathology, and the gene and protein expression of key RAS components. In addition, the blocker losartan was used from 4 weeks of age through 16 weeks of age to investigate the regulatory mechanisms of abnormal local RAS on metabolic activity in the IVF offspring liver. RESULTS: The growth trajectories of IVF offspring body and liver weights were different from those of naturally pregnant offspring. Impaired glucose tolerance (IGT) and insulin resistance (IR) occurred in IVF-conceived male offspring. After continuous HFD feeding, male offspring in the IVF group underwent earlier and more severe IR. Furthermore, there was a trend of lipid accumulation in the livers of chow-fed IVF offspring. Hepatic steatosis was also more serious in the IVF offspring after HFD treatment. Type 1 receptor (AT1R), which is the primary receptor mediating the action of angiotensin (Ang) II, has been confirmed to be upregulated in IVF offspring livers. Losartan reduced or even eliminated most of the significant differences between the IVF and NC groups after HFD consumption. CONCLUSIONS: The upregulation of AT1R expression in the liver increased the activity of the local RAS, resulting in abnormal glucose and lipid metabolism and lipid accumulation in the liver, significantly increasing the risk of nonalcoholic fatty liver disease (NAFLD) in IVF offspring.

Analysis of the guidance and predictive value of uterine artery flow parameters in patients with recurrent spontaneous abortion.

OBJECTIVE: To analyze the uterine artery blood flow parameters of patients with recurrent spontaneous abortion (RSA) at different gestational ages and to investigate the effects of aspirin and low molecular weight heparin (LMWH) on uterine artery blood flow parameters and pregnancy outcomes. METHODS: This was a retrospective cohort study involving analysis of clinical data for 140 patients: 47 in an aspirin group, 49 in a combination group, and 44 in a control group. The uterine artery blood flow parameters of the three groups in the middle luteal period and 10th, 12th, 16th, and 20th gestational weeks were compared. Trends in uterine artery flow parameters were predicted by function fitting, and the uterine artery flow parameters and pregnancy outcomes between different drug administration regimens were compared. RESULTS: With increasing gestational age, the uterine artery blood flow parameters of the three groups gradually decreased. In the middle luteal phase, the uterine artery blood flow parameters (mRI, mPI, mS/D) of the recurrent spontaneous abortion group, that is, the aspirin and combination groups, were significantly higher than those of the control group. Uterine artery blood flow parameters from 10 to 20 weeks of gestation were as follows: combined group < aspirin group < normal pregnancy group. The mean resistance index (mRI) in the combination group decreased most rapidly compared with the aspirin group between 10 and 20 weeks of gestation. The live birth rate was higher in the combination group than in the aspirin group. CONCLUSIONS: Both aspirin and aspirin combined with LMWH can reduce uterine artery blood flow parameters, and combination therapy is superior to aspirin alone. In the RSA group, the rate of mRI decline may predict pregnancy outcome to some extent. Combination therapy can improve the live birth rate and reduce the miscarriage rate.

Current status and reflections on fertility preservation in China.

PURPOSE: With the progress of medical technology and renovated conception of fertility, the prospective studies and practice of fertility preservation are drawing more and more attention from medical workers. With the largest population of over 1.4 billion, China makes the experience accumulated in fertility preservation efforts even more relevant. This article summarizes China's experience and shares it with the world to promote the healthy development of fertility preservation. METHODS: This study was based on multiple Chinese expert consensuses on fertility preservation issued in 2021 and the current national regulations and principles, compared with the latest advice and guidelines issued by global reproductive authorities such as the ASRM and ESHRE. Summarize the experience and reflection of Chinese scholars in the process of fertility preservation. RESULTS: This study reports on the current situation of fertility preservation in China, sharing the Chinese experience gained in the process of development, and offering Chinese reflections on worrying issues. CONCLUSION: Fertility preservation is a medical and social issue of reproductive health security, which is conducive to the sound development of the world population and social production.

WT1 influences apoptosis and proliferation of immature mice granular cells through regulation of the wnt/ß-catenin signal pathway.

It was to study the influence of Wilms tumor suppressor gene (WT1) on ovarian granular cells (GCs) in mice, and the molecular mechanism involved. LV-WT1 short hairpin ribonucleic acid (shRNA) vector was used to downregulate WT1 expression in granular cells (GCs). The effects of WTI on proliferation and apoptosis of GCs were investigated. Western blot and qRT-PCR were used to assay the mRNA and protein expressions of Bax/bcl-2 in GCs transfected with LV-WT1-RNAi. The expression levels of SUZ12, Wnt5a, Wnt11, Wnt4, Wnt3a, Wnt2 mRNA in GCs were also determined. LV-WT1-RNAi significantly reduced WT1 expression, increased apoptosis and inhibited proliferation of GCs. The inhibition of WT1 had no significant effect on the expression of bcl-2 in GCs. The expressions of Wnt2, Wnt4 and Wnt5a were augmented in WT1-knockdown GCs, relative to non-transfected cells. WT1 activation is necessary for maintaining early survival of GCs in follicles via activation of the Wnt/ß-catenin signal pathway.

[Analysis of the follow-up results concerning pregnancy, delivery and infants after assisted reproductive technique with GnRH-a for luteal support].

OBJECTIVE: To investigate the results of follow-up visits of pregnancy course, delivery and infants of women who got clinically pregnant by assisted reproductive technique after gonadotropin-releasing hormone agonist (GnRH-a) added for luteal support, and to analyse the influence of adding GnRH-a in luteal support on the safety of mother and infant. METHODS: A retrospective analysis was carried out on the medical record from 215 patients who got clinically pregnant after luteal phase long regimen fresh-cycle transfer was operated. According to the differences in luteal support methods, the patients were assigned to Group A (124 patients, progesterone+dydrogesterone group), Group B (91 patients, GnRH-a added group). The patients' pregnancy course, delivery time, and the growth and development of infants within 1-2 years were followed up. RESULTS: (1) There was no obvious difference between Group A and Group B in terms of the abortion ratio during the early pregnancy (8.1%, 12.1%), the rate of abortion villous deformity (50.0%, 9.1%), the rate of heterotopic pregnancy (10.5%, 5.5%) and rate of twin pregnancy (19.4%, 28.6%; all P>0.05). (2) Compared to group A, during the middle and late pregnancy of single or twin pregnancy in Group B , there was no obvious difference in the rate of fetal chromosomal abnormality, organ malformation incidence, late abortion rate and stillbirth rate (all P>0.05). (3) As to childbirth, in the case of twin pregnancy, there was a higher rate of premature delivery (60.0%, 39.1%; P=0.041), as well as rate of lower birth weight of newborn (56.0%, 34.8%; P=0.037) in group B. (4) The statistics on general growth and development as well as infantile common diseases within 2 years after birth indicated that there was no obvious difference between the two groups in single birth and twin birth subgroup (all P>0.05). CONCLUSION: On the basis of controlling of implanted embryos and reducing the occurrence of twins, GnRH-a luteal support maybe relatively safe and effective.

Exposure to nicotine during pregnancy and altered learning and memory in the rat offspring.

INTRODUCTION: Prenatal exposure to nicotine can cause many fetal developmental problems. This study determined the influence of nicotine during pregnancy on the development of cognitive behavior in the offspring. METHODS: Nicotine was administered to pregnant rats through implanted osmotic mini-pumps at 6mg/kg/day and flow rate of 60 µl/day for whole pregnancy from gestational day 4. Fetal and offspring body and brain weight was measured. Learning and memory were tested in adult offspring with Morris water maze; Learning and memory-related receptors were measured. RESULTS: The results showed that exposure to prenatal nicotine (PN) not only caused fetal growth restriction, but also had long-term effects on learning and memory in the offspring. The PN offspring exhibited longer escape latency regardless of sex. The number of passing the platform was significantly less in the PN offspring than that of the control. The expression of messenger RNA (mRNA) and protein of N-methyl-D-aspartic acid receptor (NMDAR) in the hippocampus was significantly increased, whereas alpha7 nicotinic acetylcholine receptor (α7 nAChR) protein was decreased with unchanged α7 nAChR mRNA in the PN offspring. CONCLUSION: The data provided novel information on the PN-affected development in learning and memory in the offspring, suggesting that α7 nAChR and NMDAR1 in the hippocampus might be the targets for actions of PN in association with memory impairment.

The mechanisms of MicroRNA 21 in premature ovarian insufficiency mice with mesenchymal stem cells transplantation : The involved molecular and immunological mechanisms.

Umbilical cord-derived mesenchymal stem cell (UCMSC) transplantation has been deeply explored for premature ovarian insufficiency (POI) disease. However, the associated mechanism remains to be researched. To explore whether and how the microRNA 21 (miR-21) functions in POI mice with UCMSCs transplantation, the autoimmune-induced POI mice model was built up, transplanted with or without UCMSCs transfect with the LV-hsa-miR-21-5p/LV-hsa-miR-21-5p-inhibition, with the transfection efficiency analyzed by QRT-PCR. Mice hormone secretion and the anti-Zona pellucida antibody (AZPAb) levels were analyzed, the ovarian morphological changes and folliculogenesis were observed, and the ovarian apoptosis cells were detected to evaluate ovarian function. The expression and localization of the PTEN/Akt/FOXO3a signal pathway-related cytokines were analyzed in mice ovaries.Additionally, the spleen levels of CD8 + CD28-T cells were tested and qualified with its significant secretory factor, interleukin 10 (IL-10). We found that with the LV-hsa-miR-21-5p-inhibition-UCMSCs transplantation, the mice ovarian function can be hardly recovered than mice with LV-NC-UCMSCs transplantation, and the PTEN/Akt/FOXO3a signal pathway was activated. The expression levels of the CD8 + CD28-T cells were decreased, with the decreased levels of the IL-10 expression. In contrast, in mice with the LV-hsa-miR-21-5p-UCMSCs transplantation, the injured ovarian function can be reversed, and the PTEN/AKT/FOXO3a signal pathway was detected activated, with the increased levels of the CD8 + CD28-T cells, and the increased serum levels of IL-10. In conclusion, miR-21 improves the ovarian function recovery of POI mice with UCMSCs transplantation, and the mechanisms may be through suppressing the PTEN/AKT/FOXO3a signal pathway and up-regulating the circulating of the CD8 + CD28-T cells.

LncRNA HOTAIR regulates autophagy and proliferation mechanisms in premature ovarian insufficiency through the miR-148b-3p/ATG14 axis.

Premature ovarian insufficiency (POI) is a serious disease significantly affecting the physical and mental health of women of reproductive age, not just impacting fertility outcomes. Ovarian damage due to chemotherapy remains a major cause of this condition. Recent studies have indicated the involvement of the long non-coding RNA HOTAIR in the progression of various diseases, showcasing important biological functions, yet its role in POI remains unclear. We conducted microarray dataset analysis and qRT-PCR experiments, demonstrating downregulation of HOTAIR expression in ovarian tissue and granulosa cells. Various functional experiments using plasmids overexpressing HOTAIR confirmed its promotion of cisplatin-induced granulosa cell autophagy and proliferation. Mechanistically, dual-luciferase assays showed that HOTAIR modulates ATG14 levels in POI by binding miR-148b-3p, thereby enhancing levels of autophagy and proliferation. In this study, we first explored the impact of miR-148b-3p on POI and found that overexpression of miR-148b-3p reversed the promotion of autophagy and proliferation induced by HOTAIR overexpression. The inhibitory effect of miR-148b-3p inhibitor on KGN cell autophagy and proliferation improvement could also be reversed by silencing ATG14. Overall, our findings indicate the promoting role of HOTAIR in POI and its potential as a biomarker for POI by modulating the miR-148b-3p/ATG14 axis to improve mechanisms of autophagy and proliferation in POI.

Trehalosemodulates OVRAS to improve oxidative stress and apoptosis in KGN cells and ovaries of PCOS mice.

The etiology of polycystic ovary syndrome (PCOS) is complex and variable, and there is no exact cause or good treatment method. Most of the methods of hormones are used to temporarily meet the needs of patients. Experimental evidence has shown that trehalose has, anti-apoptotic, anti-oxidative, glucose-lowering, and insulin resistance effects. However, whether trehalose has a therapeutic effect on PCOS is unknown. It has been reported that the ovarian renin-angiotensin system (OVRAS) is involved in the development of PCOS, but it has not been fully elucidated. This study aims to explore the effect of trehalose on PCOS and elucidate the related OVRAS mechanism. We first observed that body weight, estrous cycle, ovarian follicles at all levels, glucose tolerance, serum hormones, and insulin resistance were improved by trehalose treatment in the PCOS mouse model. Moreover, trehalose treatment also ameliorated ovarian oxidative stress and apoptosis in PCOS mice, as determined by TUNNEL apoptosis staining, total SOD in ovarian homogenate, and WB assay. OVRAS mainly involves two classic pathways, namely the ACE/AngII/AT1R/AT2R, and ACE2 / Ang1-7/ MASR, Which play different functions. In PCOS mouse ovaries, we found that ACE/AngII/AT1R was up-regulated and ACE2/Ang1-7/MASR and AT2R were down-regulated by PCR and WB experiments, However, trehalose treatment changed its direction. In addition, we also found that trehalose ameliorated DHEA-induced oxidative stress and apoptosis in KGN by PCR and WB experiments, mainly by down-regulating ACE/AngII/AT1R. Our study shows that trehalose improves symptoms of PCOS mainly by down-regulating ACE/AngII/AT1R, revealing a potential therapeutic target for PCOS.

Clinical characteristics and prognostic factors of male breast cancer in China.

Purpose: This study aimed to explore the clinical characteristics of male breast cancer (MBC) patients and the factors influencing their prognosis. Methods: We conducted a retrospective case series analysis of 117 MBC cases who were treated at Zhejiang Cancer Hospital from 2009 to 2022. Cox proportional hazard model was used to identify prognostic factors of MBC. Nomogram was constructed based on these factors, which was further evaluated by C-index and calibration curves. Results: A total of 115 MBC cases were finally included in our analyses, with median diagnosis age of 59 years. Of these cases, 80.0% were estrogen receptor (ER) positive, 79.2% were progesterone receptor (PR) positive, 48.7% were human epidermal growth factor receptor 2 (HER2) negative, and 42.6% had Ki67 levels higher than 15%. 108 (93.9%) cases underwent radical mastectomy, while only 3 (2.6%) received breast-conserving surgery. The Logrank test suggested that lymphocyte-to-monocyte ratio (LMR) was negatively associated with both overall survival (OS) and disease-free survival (DFS) of MBC, while platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) were only positively associated with OS (all P-values < 0.05). Multivariate regression analysis showed that age (HR 1.08, 95% CI 1.03-1.13) was significant prognostic factors for OS. Meanwhile, age (HR 1.06, 95% CI 1.02-1.10), histological differentiation grade (poorly differentiated/undifferentiated vs. well-differentiated: HR 2.55, 95% CI 1.05-6.17), and TNM stage (IV vs. I: HR 31.59, 95% CI 6.01-165.93) were also significant prognostic factors for DFS. Nomograms were developed for DFS, with C-indexes of 0.782, indicating good predictive performance. Conclusion: Increased age, bigger tumor size, higher TNM stage, and lower histological differentiation grade were associated with poor MBC prognosis, and LMR, PLR, and NLR might be potential predictors for MBC prognosis.

Impacts of the COVID-19 pandemic on Chinese assisted reproductive technology institutions and human sperm banks: reflections in the post-pandemic era.

OBJECTIVE: The COVID-19 pandemic has been the most serious public health emergency encountered in modern assisted reproductive technology (ART) development. In order to identify lessons learned, this study reviews the effect of the pandemic on ART institutions and human sperm banks in China, and summarizes the experiences and reflections of Chinese scholars post-pandemic era. METHODS: This review is based on multiple consensus statements on the COVID-19 pandemic issued by Chinese experts as well as current national regulations and principles in ART institutions and human sperm banks to document the current situation of ART services in China, describe the impact of the pandemic on these services, and offer Chinese reflections on worrying issues in the post-pandemic era. RESULTS: China reached one million ART cycles in 2016, and there are currently 540 ART medical institutions and 27 human sperm banks, with 540 licensed for AIH, 91 for AID, 415 for conventional IVF and ICSI and 85 for PGT. Of these, only 4 institutions carry out 10,000 cycles or more annually, and the proportion of institutions with less than 1,000 cycles has reached 66%, which means that a considerable number of ART institutions are still not saturated. As a consequence of the COVID-19 pandemic, 63.6% of ART providers and 95.5% of human sperm banks suspended operations. By the end of May 2020, China, as an early country affected by the pandemic achieved a national resumption rate of ART medical services of 99.2% and that of human sperm banks of 100.0%. Reports from the first and largest human sperm bank in China showed that qualification, semen concentration and sperm viability rates measured at primary screening have significantly decreased post-pandemic. Much like in other countries, Chinese experts developed a consensus on prevention and control measures during the pandemic. In principle, all ART activities should be suspended during acute phases of infection spread. Chinese scholars highlight that attention should be paid to young patients with fertility requirements during and after COVID-19, and emphasize the importance of fertility evaluation and clinical intervention. In addition, couples should be reminded that during ART treatment, disinfectants should not be used excessively to minimize risks of damaging the reproductive system, gametes and zygotes. At the same time, timely and reasonable guidance for tackling negative emotions from stress response is needed to provide reassurance and to avoid irrational fear and excessive stress. Seminal parameters should be re-examined 2 months after SARS-CoV-2 vaccination, and ART treatments recommenced if no abnormalities are detected. CONCLUSIONS: Given the growing frequency of outbreaks of global infectious diseases in recent years, ART institutions and human sperm banks should pay attention to improving their prevention and control capabilities. To a certain extent, decisions and measures adopted in China during COVID-19 pandemic are worthy of recognition and acceptance. Chinese scholars have discussed, proactively responded to and understand the key issues surrounding ART development during the pandemic with the aim of contributing to the substantial progress and healthy development of ART services in the world.

Central angiotensin I increases swallowing activity and oxytocin release in the near-term ovine fetus.

The brain renin-angiotensin system (RAS) plays an important role in hydromineral and neuroendocrine balance. Although previous studies showed that exogenous angiotensin (Ang) II increased dipsogenic and vasopressin responses in near-term fetuses, little is known about the functional development of fetal endogenous brain RAS in the regulation of body fluid homeostasis. To determine the functional development of the central angiotensin-converting enzyme (ACE) in utero, we investigated the electrocortical (ECoG) activity, swallowing activity, oxytocin (OT) release, and c-fos expression in response to intracerebroventricular Ang I administration in the near-term fetal lamb. Ang I did not change fetal low-voltage (LV) and high-voltage (HV) ECoG temporal distributions, but increased fetal swallowing activity during LV ECoG (1.0±0.1 to 3.5±0.4 swallows/min). Additionally, Ang I evoked an increase in c-fos-immunoreactivity in putative dipsogenic centers, including the supraoptic and paraventricular nuclei of the hypothalamus, accompanied by an increase in fetal plasma OT levels. The expression of c-fos was demonstrated in OT neurons in the hypothalamus. The Ang I-mediated increase in fetal swallowing and plasma OT was inhibited by captopril. These results demonstrate the functional development of the fetal brain ACE system in the last trimester of gestation, which plays an important role in the RAS-mediated dipsogenic response and OT release in the regulation of body fluid homeostasis.

The effect of folic acid on ovine fetuses in utero during late gestation.

To investigate whether folic acid would have toxic effects on fetal cardiac, hepatic, and renal functions, this was the first in utero fetal study testing acute effects of folic acid at the last third of gestation. Folic acid (5 mg/day) or 0.9% saline as the control was intragastricly administrated into pregnant ewes. Both maternal and fetal blood were analyzed for pH, PO(2), PCO(2), SO(2)%, hemoglobin, hematocrit, glucose, lactic acid, osmolality, Na(+), and K(+) concentrations. Maternal and fetal cardiovascular functions were assessed by examining cardiac enzymes and cardiovascular responses in vivo. Fetal hepatic and renal functions were examined by analysis of biochemistry index and renal excretion. Folic acid did not alter the blood values in both ewes and fetuses. Cardiac enzyme activities remained unchanged, and no alteration in cardiovascular responses was observed. Folic acid did not affect fetal urine volume, urine electrolytes, and osmolality. Enzyme activities related to hepatic and renal functions were not changed. In addition, maternal application of folic acid had no effect on maternal and fetal lipid profile. The results showed that folic acid used (5 mg/day) during the last third of gestation did not cause biochemical changes related to cardiac, hepatic, and renal functions in both maternal and fetal sheep, providing new information for use of folic acid during late pregnancy.

COVID-19 and Male Reproduction: A Thorny Problem.

With the global epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the increasing number of infections, little is known about how SARS-CoV-2 affects the male reproductive system during infection or after recovery. Based on the existing research data, we reviewed the effects of SARS-CoV-2 on the male reproductive system and discussed its possible mechanism of action. SARS-CoV-2 enters host cells through the angiotensin-converting enzyme 2 (ACE2)/transmembrane serine protease 2 (TMPRSS2) pathway, and males are more susceptible than females. After infection, immunopathological damage is noticed in the testicles, and the semen index is significantly reduced. Second, abnormalities of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) levels were also observed, suggesting that there may be dysfunction of the hypothalamic-pituitary-gonadal (HPG) axis. Even after recovery, the effect of SARS-CoV-2 on the male reproductive system can last for at least a period. There are still many unresolved questions about the effect of SARS-CoV-2 infection on the male reproductive tract. Other receptors involved during the invasion of human cells by SARS-CoV-2 remain to be identified. Will the mutation of SARS-CoV-2 increase the diversity of receptors? How does SARS-CoV-2 affect the HPG axis? The long-term effects of SARS-CoV-2 on the male reproductive system remain to be evaluated. SARS-CoV-2 infection can affect male reproductive function. Standard treatment strategies should be developed in time to protect the fertility of infected patients. For recovered patients with fertility requirements, fertility assessments should be performed and professional fertility guidance should be provided at the same time.

Construction of a ceRNA-based lncRNA-mRNA network to identify functional lncRNAs in premature ovarian insufficiency.

Premature ovarian insufficiency, characterized by ovarian infertility and low fertility, has become a significant problem in developed countries due to its propensity for late delivery. It has been described that the vital role of lncRNA in the development and progression of POI. The aim of this work was to create a POI-based lncRNA-mRNA network (POILMN) to recognize key lncRNAs. Overall, differently expressed mRNAs (DEGs) and differently expressed lncRNAs (DELs) were achieved by using the AnnoProbe and limma R packages. POI-based lncRNA-mRNA network (POILMN) construction was carried out using the tinyarray R package and hypergeometric distribution. To identify key lncRNAs, we used CentiScaPe plug-in Cytoscape as a screening tool. In total, 244 differentially expressed lncRNAs (DELs) and 288 differentially expressed mRNAs (DEGs) were obtained in this study. Also, 177 lncRNA/mRNA pairs (including 39 lncRNAs and 86 mRNAs) were selected using the hypergeometric test. Finally, we identified four lncRNA (HCP5, NUTM2A-AS1, GABPB1-IT1, and SMIM25) intersections by topological analysis between two centralities (degree and betweenness), and we explored their subnetwork GO and KEGG pathway enrichment analysis. Here, we have provided strong evidence for a relationship with apoptosis, DNA repair damage, and energy metabolism terms and pathways in the key lncRNAs in our POI-based lncRNA-mRNA network. In addition, we evaluated the localization information of genes related to POI and found that genes were more distributed on chromosomes 15, 16, 17, and 19. However, more experiments are needed to confirm the functional significance of such predicted lncRNA/mRNA. In conclusion, our study identified four long non-coding RNA molecules that may be relevant to the progress of premature ovarian insufficiency.

Nomogram incorporating ultrasonic markers of endometrial receptivity to determine the embryo-endometrial synchrony after in vitro fertilization.

Background: A successful pregnancy using in vitro fertilization and embryo transfer (IVF-ET) requires a receptive endometrium, good-quality embryos, and a synchronized embryo-endometrial dialogue. Although embryo quality and endometrial receptivity (ER) have been fully assessed to exclude substandard conditions, the probability of successful ET is relatively low. Currently, embryo-endometrial synchrony is considered to be a possible explanation, because delayed, advanced, or narrowed window of implantation (WOI) may lead to ET failure. Objective: This study aims to establish a nomogram incorporating a series of ultrasonic ER markers on the day before implantation to assess the embryo-endometrial synchrony, which may contribute to the improvement of clinical pregnancy outcomes. Methods: Totally 583 women with 1135 complete IVF cycles were retrospectively analyzed. Among them, 357 women with 698 cycles and 226 women with 437 cycles were assigned to the training and validation cohorts, respectively. Ultrasonic ER markers obtained on the day before implantation were collected for analyses. In the training cohort, the screened correlates of clinical pregnancy failure were utilized to develop a nomogram for determining whether an infertile woman is suitable for the ET next day. This model was validated both in the training and validation cohorts. Results: Spiral artery (SA) resistance index (RI), vascularisation index (VI), and flow index (FI) were independently associated with the ET failure (all P < 0.05). They were served as the components of the developed nomogram to visualize the likelihood of implantation failure in IVF-ET. This model was validated to present good discrimination and calibration, and obtained clinical net benefits both in the training and validation cohorts. Conclusion: We developed a nomogram that included SA-RI, VI, and FI on the day before implantation. It may assist physicians to identify patients with displaced WOI, thus avoiding meaningless ET prior to implantation.

Development of fetal brain renin-angiotensin system and hypertension programmed in fetal origins.

Since the concept of fetal origins of adult diseases was introduced in 1980s, the development of the renin-angiotensin system (RAS) in normal and abnormal patterns has attracted attention. Recent studies have shown the importance of the fetal RAS in both prenatal and postnatal development. This review focuses on the functional development of the fetal brain RAS, and ontogeny of local brain RAS components in utero. The central RAS plays an important role in the control of fetal cardiovascular responses, body fluid balance, and neuroendocrine regulation. Recent progress has been made in demonstrating that altered fetal RAS development as a consequence of environmental insults may impact on "programming" of hypertension later in life. Given that the central RAS is of equal importance to the peripheral RAS in cardiovascular regulation, studies on the fetal brain RAS development in normal and abnormal patterns could shed light on "programming" mechanisms of adult cardiovascular diseases in fetal origins.

Central angiotensin I increases fetal AVP neuron activity and pressor responses.

Angiotensin (Ang) II plays a critical role in cardiovascular homeostasis and neuroendocrine regulation. Little is known about whether central angiotensin-converting enzyme (ACE) is functional in the fetal brain. We investigated cardiovascular and neuroendocrinological responses to intracerebroventricular (icv) application of Ang I in the chronically prepared near-term ovine fetus in utero and examined the action sites marked by c-fos expression in the fetal hypothalamus. ACE mRNA was detected in the specific central areas. Intracerebroventricular Ang I significantly increased fetal blood pressure and c-fos expression in the supraoptic nuclei (SON) and the paraventricular nuclei (PVN) in the hypothalamus, accompanied by an increase of fetal plasma arginine vasopressin (AVP). Double labeling demonstrated that AVP neurons in the fetal SON and PVN were expressing c-fos. Captopril, an inhibitor of ACE, significantly suppressed fetal pressor responses and plasma AVP. Double labeling experiments showed colocalization of AT(1) receptor (AT(1)R) and c-fos expression in both SON and PVN following icv Ang I. The results indicate that central endogenous ACE has been functional at least at the last third of gestation and the endogenous brain renin-angiotensin system-mediated pressor responses and AVP release via AT(1)Rs by acting at the sites consistent with the cardiovascular network in the hypothalamus.