Analysis on pregnancy outcomes and risk factors of cervical polypectomy during the first and second trimester pregnancy.

AIM: To evaluate the risk factors of miscarriage in patients attempted cervical polypectomy during the first and second trimester pregnancy. METHODS: Pregnant women with singleton infants who underwent cervical polypectomy during the first and second trimester between January 2013 and May 2019 were investigated. The study retrospectively reviewed the clinical features and pregnancy outcomes after cervical polypectomy. A multivariable regression was performed to predict the risk factors of miscarriage. RESULTS: A total of 307 pregnant females were eventually included in our study. Twenty-seven patients (8.8%, 27/307) had a miscarriage before 28 weeks, 37 patients (12.1%, 37/307) had a preterm delivery. After univariate analysis, we found that the presence of decidual polyps and vaginal bleeding after polypectomy were the risk factors for miscarriage. Moreover, the incidence of miscarriage was significantly higher in the patients with decidual polyps than in those with endocervical polyps (14.9% vs. 5.6%, p = 0.010). CONCLUSIONS: The most suitable hemostasis method should be taken in the cervical polypectomy during pregnancy. The risk of miscarriage associated with polypectomy during pregnancy is higher in females with decidual polyps. If decidual polyps are highly suspected and they do not cause excessive vaginal bleeding and can be ruled out the possibility of malignancy, conservative treatment may lead to a better outcome.

Altered expression of DNA damage repair genes in the brain tissue of mice conceived by in vitro fertilization.

Our previous study revealed a higher incidence of gene dynamic mutation in newborns conceived by IVF, highlighting that IVF may be disruptive to the DNA stability of IVF offspring. However, the underlying mechanisms remain unclear. The DNA damage repair system plays an essential role in gene dynamic mutation and neurodegenerative disease. To evaluate the long-term impact of IVF on DNA damage repair genes, we established an IVF mouse model and analyzed gene and protein expression levels of MSH2, MSH3, MSH6, MLH1, PMS2, OGG1, APEX1, XPA and RPA1 and also the amount of H2AX phosphorylation of serine 139 which is highly suggestive of DNA double-strand break (γH2AX expression level) in the brain tissue of IVF conceived mice and their DNA methylation status using quantitative real-time PCR, western blotting and pyrosequencing. Furthermore, we assessed the capacity of two specific non-physiological factors in IVF procedures during preimplantation development. The results demonstrated that the expression and methylation levels of some DNA damage repair genes in the brain tissue of IVF mice were significantly changed at 3 weeks, 10 weeks and 1.5 years of age, when compared with the in vivo control group. In support of mouse model findings, oxygen concentration of in vitro culture environment was shown to have the capacity to modulate gene expression and DNA methylation levels of some DNA damage repair genes. In summary, our study indicated that IVF could bring about long-term alterations of gene and protein expression and DNA methylation levels of some DNA damage repair genes in the brain tissue and these alterations might be resulted from the different oxygen concentration of culture environment, providing valuable perspectives to improve the safety and efficiency of IVF at early embryonic stage and also throughout different life stages.

Proximal Fallopian Tubal Embolization by Interventional Radiology prior to Embryo Transfer in Infertile Patients with Hydrosalpinx: A Prospective Study of an Off-label Treatment.

STUDY OBJECTIVE: To evaluate in vitro fertilization (IVF) outcomes of proximal fallopian tube embolization by interventional radiology compared with laparoscopic salpingectomy before embryo transfer (ET) in patients with hydrosalpinx. DESIGN: A single-center, off-label, nonrandomized prospective study. SETTING: Academic university hospital. PATIENTS: One hundred fifty-five patients with hydrosalpinx were identified on ultrasound or hysterosalpingography desiring IVF between April 2016 and December 2017. INTERVENTIONS: Radiologically guided tubal occlusion with embolization microcoils (RTO-EM) and laparoscopic salpingectomy. MEASUREMENTS AND MAIN RESULTS: Of the 155 analyzed patients, 42 were treated with RTO-EM and 113 with laparoscopic salpingectomy. The subsequent IVF outcomes, including implantation, clinical pregnancy, miscarriage, ectopic pregnancy, and ongoing pregnancy (i.e., a fetal heartbeat on ultrasound beyond 10 weeks) were compared between the 2 groups. Implantation and clinical pregnancy per ET cycle in the RTO-EM group were similar to that of the salpingectomy group (26.7% vs 30.2% [p = .51] and 39.0% vs 45.3% [p = .40], respectively), with a similar miscarriage rate. There was no statistically significant difference in ectopic pregnancies between the 2 groups. Moreover, no difference was detected in ongoing pregnancy per cycle between the 2 groups (33.9% vs 41.2%; p = .32). The ongoing-pregnancy rate per patient following RTO-EM was 47.6% (20 of 42) compared with 61.9% (70 of 113) following salpingectomy (odds ratio, 0.56; 95% confidence interval, 0.27-1.14; p = .11). CONCLUSION: Pregnancy in the RTO-EM group was comparable to the salpingectomy group in patients with hydrosalpinx before ET treatment. RTO-EMs may be an alternative to salpingectomy for patients with hydrosalpinx planning for IVF-ET.

Urinary bisphenol A concentration is correlated with poorer oocyte retrieval and embryo implantation outcomes in patients with tubal factor infertility undergoing in vitro fertilisation.

Bisphenol A (BPA) is a substance ubiquitously present in the environment, and its toxicity on reproductive function has been well characterised in animal models. However, it is still controversy about the effects of BPA exposure on human female reproduction. Therefore, in the present study, the associations of urinary BPA concentration with the outcomes of in vitro fertilisation (IVF) and embryo transfer from fresh and frozen cycles were analysed in the same cohort. 351 women who underwent IVF treatment from September 2013 to October 2016, at the Centre of Reproductive Medicine in the Women's Hospital School of Medicine at Zhejiang University were recruited. Single-spot urine samples were collected on the day of oocyte retrieval to detect BPA using solid-phase extraction and liquid chromatography coupled with tandem mass spectrometry. A multivariable generalised linear mixed model was used to evaluate the association between the urinary BPA concentration and IVF outcomes. After adjustment for age, body mass index, baseline follicle-stimulating hormone level, baseline oestradiol level, and antral follicle count, a significant decrease in the number of retrieved oocytes and in the rates of clinical pregnancy and implantation was observed in the patients with a high urinary BPA concentration. We concluded that BPA exposure exert negative effects on oocyte retrieval and embryo implantation in women undergoing IVF.

Decreased expression of MRE11 and RAD50 in testes from humans with spermatogenic failure.

PURPOSE: To assess testicular mRNA and protein expression levels of MRE11 and RAD50 in human azoospermia patients. METHODS: Patients diagnosed with maturation arrest at the spermatocyte stage (MA) and Sertoli cell-only syndrome (SCOS) were recruited through diagnostic testicular biopsy. Patients with normal spermatogenesis were studied as controls. In addition, knockdown of MRE11 and RAD50 was performed in GC-2spd(ts) cells to investigate their roles in cellular proliferation and apoptosis. RESULTS: mRNA and protein expression levels of MRE11 and RAD50 were measured using quantitative polymerase chain reaction, western blotting, and immunohistochemistry, respectively. Knockdown of both MRE11 and RAD50 utilized transfection with small interfering RNAs. CONCLUSION: Our findings demonstrated altered expression levels of MRE11 and RAD50 in human testes with MA and SCOS, and showed that these alterations might be associated with impaired spermatogenesis. These results offer valuable new perspectives into the molecular mechanisms of male infertility.

The effect of local aspiration and methotrexate injection on live interstitial pregnancy coexisting with live intrauterine pregnancy after assisted reproductive technology.

AIM: To share the experience of local aspiration and instillation of methotrexate (MTX) to selective reduction of live interstitial pregnancy and to evaluate its clinical effect and the outcome of intrauterine pregnancy. METHODS: Twelve patients with heterotopic interstitial pregnancy were enrolled at Women's Hospital, Zhejiang University School of Medicine, from 2006 to 2017. All the pregnancies were derived from assisted reproductive technology (ART). The transvaginal aspiration to interstitial pregnancy sac and local instillation of MTX (range from 12.5 to 30 mg) were performed for the patients under ultrasound-guide. The prognosis and pregnancy outcomes were followed up. RESULTS: No severe side effects of medical treatment were observed in all patients. Three cases underwent subsequent laparotomy cornual resection, and no perioperative complications were found in these three patients. Twelve patients gave birth to 13 healthy infants without congenital anomalies. The average birth weight and gestational age was 2837 g (SD ± 605 g) and 36.8 weeks (SD ± 2.4 weeks). No growth anomalies and mental retardation were observed in live birth offspring. CONCLUSION: The transvaginal ultrasound-guided aspiration and injection of MTX might be a feasible alternative treatment for heterotopic interstitial pregnancy when vital signs of patients are stable.

Alteration in the expression of the renin-angiotensin system in the myocardium of mice conceived by in vitro fertilization.

Epidemiological studies have revealed that offspring conceived by in vitro fertilization (IVF) have an elevated risk of cardiovascular malformations at birth, and are more predisposed to cardiovascular diseases. The renin-angiotensin system (RAS) plays an essential role in both the pathogenesis of congenital heart disease in fetuses and cardiovascular dysfunction in adults. This study aimed to assess the relative expression levels of genes in the RAS pathway in mice conceived using IVF, compared to natural mating with superovulation. Results demonstrated that expression of the angiotensin II receptor type 1 (AGTR1), connective tissue growth factor (CTGF), and collagen 3 (COL3), in the myocardial tissue of IVF-conceived mice, was elevated at 3 weeks, 10 weeks, and 1.5 years of age, when compared to their non-IVF counterparts. These data were supported by microRNA microarray analysis of the myocardial tissue of aged IVF-conceived mice, where miR-100, miR-297, and miR-758, which interact with COL3, AGTR1, and COL1 respectively, were upregulated when compared to naturally mated mice of the same age. Interestingly, bisulfite sequencing data indicated that IVF-conceived mice exhibited decreased methylation of CpG sites in Col1. In support of our in vivo investigations, miR-297 overexpression was shown to upregulate AGTR1 and CTGF, and increased cell proliferation in cultured H9c2 cardiomyocytes. These findings indicate that the altered expression of RAS in myocardial tissue might contribute to cardiovascular malformation and/or dysfunction in IVF-conceived offspring. Furthermore, these cardiovascular abnormalities might be the result of altered DNA methylation and abnormal regulation of microRNAs.

Elevated RON protein expression in endometriosis and disease-associated ovarian cancers.

BACKGROUND: Recepteur d'origine nantais (RON) protein expression has been demonstrated to correlate with tumor progression, metastasis, and prognosis, and its mRNA expression increases in deeply infiltrating endometriotic lesions. However, it remains unclear whether RON protein expression also increases in endometriotic lesions, and may be a risk factor of malignant transformation in endometriotic lesions. METHODS: The protein expression of RON in control (n = 19), eutopic (n = 16), and ectopic (n = 51) endometria, as well as in endometriosis-associated ovarian cancers (EAOC, n = 16) was determined by immunohistochemical (IHC) staining. RESULTS: Endometriotic lesions expressed low levels of RON protein, but no RON protein expression appeared in matched eutopic or control endometrium. EAOC exhibited high levels of RON protein. The frequency and IHC score of RON protein expression were both significantly higher in EAOC [100.0% (14/14), 5.37 ± 0.74] than those in endometriotic lesions [51.0% (26/51), 2.15 ± 1.12; P = 0.002, 0.001]. Multivariate analysis of covariance only revealed a correlation of RON protein expression and EAOC (P = 0.006), but no correlations of RON protein expression and clinical parameters (P > 0.05). CONCLUSIONS: These obtained results suggest that increased RON expression might be involved in the pathogenesis of endometriosis and disease-associated ovarian cancers.

Human sperm devoid of germinal angiotensin-converting enzyme is responsible for total fertilization failure and lower fertilization rates by conventional in vitro fertilization.

In conventional in vitro fertilization (IVF), complete failure of fertilization occurs in 5% to 15% of treatments. Although the causes may be unclear, sperm defects appear to be the major contributor. However, a convincing test is not yet available that can predict the risk of fertilization failure. In this study, we found that germinal angiotensin-converting enzyme (gACE) (also called testicular ACE) was undetectable in sperm from patients who had total fertilization failure (TFF) and lower fertilization rates (LFRs) by IVF based on Western blot and indirect immunofluorescence analyses. Additionally, almost all of the patients without gACE on sperm (23 of 25) manifested a TT genotype of the rs4316 single-nucleotide polymorphism of ACE. Overall, our results indicate that the absence of gACE expression is responsible for TFF and LFRs by IVF. The rs4316 polymorphism of ACE might be associated with infertility in those patients. We conclude that sperm lacking gACE may be recognized before commencing IVF and that the patients may be directed instead to consider intracytoplasmic sperm injection.

[Influence of assisted reproduction technologies on genomic imprinting of embryos and offspring].

Assisted reproduction technologies (ART) include controlled ovarian hyperstimulation, in vitro fertilization-embryo transfer, intracytoplasmic sperm injection, in vitro maturation of oocytes, pre-implantation genetic diagnosis, etc. They have been used for the treatment of impaired fertility but may damage the health of offspring. The ART procedures may alter the epigenetic status of these offspring and DNA methylation may be a crucial mechanism. This paper summarizes epigenetic alterations in ART embryos and offspring, and discusses the risks.

In vitro fertilization alters growth and expression of Igf2/H19 and their epigenetic mechanisms in the liver and skeletal muscle of newborn and elder mice.

Epidemiological studies have reported a higher incidence of growth disorders among newborns conceived by in vitro fertilization (IVF), suggesting that IVF may be disruptive to the process of embryonic and fetal growth. However, the long-term effects of IVF on the growth and molecular mechanisms remain unclear. Therefore, we evaluated the body weight of IVF mice from birth to the age of 1.5 yr. In addition, we analyzed gene expression of insulin-like growth factor 2 (Igf2), H19, Igf2 receptor (Igf2r), and miR-483 and their DNA methylation status using real-time quantitative PCR, Western blot, and pyrosequencing. The results showed that when compared with the in vivo group, the body weight of IVF mice was significantly higher at birth, but lower at 3 wk; in addition, gene expression of Igf2 was significantly up-regulated, with down-regulated expression of H19 and miR-483 in both liver and skeletal muscle. At the same time, there were significant differences in the DNA methylation rates of Igf2/H19 differentially methylated regions (DMRs) and the IGF2 protein expression between the two groups. In the IVF treatment group, the differences in growth and expression disappeared at 10 wk. However, at 1.5 yr of age, aberrant expressions of Igf2/H19, Igf2r, and miR-483 and changes in DNA methylation rates in the liver or skeletal muscle were again observed in IVF mice. Our results indicate that IVF causes alterations in mouse growth during the postnatal periods that may be associated with alterations in Igf2/H19 expression and likely involve the regulation of miR-483 and the methylation status of Igf2/H19 DMRs.

Alterations in the frequency of trinucleotide repeat dynamic mutations in offspring conceived through assisted reproductive technology.

STUDY QUESTION: How does the frequency of trinucleotide repeat dynamic mutations in offspring conceived through assisted reproductive technology (ART) compare with the frequency of these mutations in control offspring conceived from spontaneous pregnancies? SUMMARY ANSWER: There is a slight increase in dynamic mutation instability in offspring conceived through ART compared with the naturally conceived offspring. WHAT IS KNOWN ALREADY: There is evidence to suggest that ART can increase the risk of birth defects and karyotypic abnormalities. However, the accumulating evidence of an association between ART and de novo genetic aberrations is controversial. STUDY DESIGN, SIZE, DURATION: A prospective clinical observational study was performed on 246 families recruited from an in vitro fertilisation (IVF) centre at a tertiary-care, university-affiliated teaching hospital from 2008 to 2012. The study included 147 ART families [75 IVF and 72 intracytoplasmic sperm injection (ICSI)] in the study group and 99 natural-conception families in the control group. PARTICIPANTS, SETTING, METHODS: Parental, umbilical cord and infant peripheral blood samples were collected, and the trinucleotide repeats of the ATN1, AR, ATXN1, ATXN3, Huntington, DMPK and FMR-1 genes were investigated between the generations; these genes were chosen due to their ability to undergo dynamic mutation. The frequencies and sizes of the mutational repeats, as well as the intergenerational instability, were measured. MAIN RESULTS AND THE ROLE OF CHANCE: In 2466 transmissions identified in the ART offspring, 2.11% (n = 52/2466) of the alleles were unstable upon transmission, while in the control group offspring, the frequency of dynamic mutation was 0.77% (n = 10/1300); this difference was statistically significant (P < 0.01). The unstable transmission alleles were detected in 32 (2.48%) of the 1288 alleles from the IVF offspring and in 20 (1.70%) of the 1178 alleles from the ICSI offspring; both of these frequencies were significantly different from that of naturally conceived offspring (0.77%) (P < 0.01 and P < 0.05, respectively). However, there were no significant differences in the sizes of the mutational repeats or in the rates of expansion or contraction among the three groups (P > 0.05). The repeat copy numbers of the examined genes were found to be within the normal ranges in all parents and infants. LIMITATIONS, REASONS FOR CAUTION: One strength of our study is the relatively large sample size; we were able to detect mutations in seven common dynamic genes, and this large sample size allowed us to detect unstable alleles. Although we observed a clear alteration in the frequency of dynamic mutation in the ART offspring compared with controls, further studies are urgently needed to confirm this observation and determine the cause of this phenomenon. WIDER IMPLICATIONS OF THE FINDINGS: DNA microsatellite analysis provides an important tool to assess genomic instability. In this study, we report an association between ART and the frequency of dynamic mutation. The instability could be a reflection of the core infertility problem, the controlled ovarian hyperstimulation and/or the in vitro culture conditions.

Alteration of fatty acid metabolism in the liver, adipose tissue, and testis of male mice conceived through assisted reproductive technologies: fatty acid metabolism in ART mice.

BACKGROUND: Lipid metabolism plays important roles in the whole process of pregnancy. Previous studies have demonstrated abnormalities of lipid metabolism in the placentas of pregnancies obtained by assisted reproductive technology (ART). Therefore, we hypothesized that ART micromanipulation may affect lipid metabolism in offspring, and focused on the fatty acid metabolism in ART male offspring in this study. METHODS: The fatty acid metabolism in the liver, adipose tissue and testis was detected. The comparison between naturally conceived (NC), controlled ovarian hyperstimulation (COH), in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) mice was made to analyze the effect of ART on offspring. The mice models in this study included two age groups: adult group and old group. The fatty acid composition and the expression of lipid metabolism-related genes were analyzed by GC-MS and qRT-PCR. RESULTS: The fatty acid composition in the liver and adipose tissue were significantly altered in ART mice, but no significant difference was found in the testis. In adipose tissue, ART mice showed decreased monounsaturated fatty acids (MUFAs) and increased polyunsaturated fatty acids (PUFAs) in both adult and old mice, while the alteration of saturated fatty acids (SFAs) in the adult disappeared in the old. In liver, the changes were much complex in adult mice, while increased MUFAs and decreased PUFAs were found in ART old mice. The activities of fatty acid metabolism-related enzymes and the expression of lipogenic and lipolytic proteins changed in ART groups, with the adult mice and old mice showing inconsistent alterations. Further analysis indicated that SFAs was closely associated with the alterations of fatty acid metabolism-related enzyme activities and the expression of lipogenic and lipolytic proteins. Furthermore, we also found that the effect of separated ART treatments on fatty acid metabolism varied with different ages and tissues. CONCLUSIONS: ART treatments had effect on the fatty acid composition in adipose tissue and liver of male mice. The alteration of SFAs content was crucial for the regulation of fatty acid composition. These changes might have potential effects on the health of ART male offspring which need further investigation.

Angiotensin-converting enzymes play a dominant role in fertility.

According to the World Health Organization, infertility, associated with metabolic syndrome, has become a global issue with a 10%-20% incidence worldwide. An accumulating body of evidence has shown that the renin-angiotensin system is involved in the fertility problems observed in some populations. Moreover, alterations in the expression of angiotensin-converting enzyme-1, angiotensin-converting enzyme-2, and angiotensin-converting enzyme-3 might be one of the most important mechanisms underlying both female and male infertility. However, as a pseudogene in humans, further studies are needed to explore whether the abnormal angiotensin-converting enzyme-3 gene could result in the problems of human reproduction. In this review, the relationship between angiotensin-converting enzymes and fertile ability is summarized, and a new procedure for the treatment of infertility is discussed.

[Retrospective Analysis of Irregular Antibodies Causing Hemolytic Disease of the Fetus and Newborn in Jiangxi Province].

OBJECTIVE: To analyze the characteristics of antibody-specific distribution, laboratory detection results of hemolytic disease of the fetus and neonatal(HDFN) caused by irregular blood group antibodies other than ABO, and its correlation with the clinical situation. METHODS: The non-ABO-HDFN cases in our hospital from October 2012 to December 2021 were selected as the research objects, and the cases diagnosed with ABO-HDFN in the same period were randomly selected as the control group, and the data of antibody specific distribution, total bilirubin, direct antibodies, maternal history, age of the children, the presence or absence of combined ABO-HDFN, and whether to exchange/transfuse blood were retrospectively analyzed. The characteristics of non-ABO-HDFN in Jiangxi province were analyzed. RESULTS: The detection rate of non-ABO-HDFN in Jiangxi province increased. Among 187 non ABO-HDFN cases, the highest percentage of Rh-HDFN was detected (94.6%). Compared with the control group of ABO-HDFN, the non-ABO-HDFN had higher mean integral value of direct antibody, higher peak total bilirubin, and longer duration. Anti-M-HDFN may have severe disease but the direct antibody weak positive/negative, it was easy missed in clinical and delayed the treatment. There is no correlation between the specificity of irregular antibodies, the sex of the child, the mother's previous childbirth history, the presence or absence of combined ABO-HDFN and the need for blood exchange/transfusion(P>0.05). CONCLUSION: The irregular antibodies of causing non ABO-HDFN in Jiangxi area are mainly Rh blood group system, followed by MNS blood group system. Understanding the characteristics of HDFN disease, serological features and the correlation with clinical indexes will help to detect and treat non ABO-HDFN in time and reduce the risk of complications.

[Study on BW.12 Subtype Caused by c.278C>T Mutation in Exon 6 of ABO Gene].

OBJECTIVE: To investigate the effect of ABO gene α-1,3-D galactosyl transferase mutation on B antigen expression and its molecular mechanism. METHODS: The proband and their family members were identified by routine serological methods, and ABO genotyping and sequence analysis were performed by polymerase chain reaction-sequence specificity (PCR-SSP) and direct sequencing of PCR products from exon 1-7 of ABO gene. The 3D structural simulation of mutant proteins was performed by bioinformatics software. The effect of gene mutation on protein structural stability was analyzed. RESULTS: The proband and his family members were subtype B. ABO genotyping indicated that the proband's genotype was Bw12/O. Gene sequencing results confirmed the presence of ABO*BW.12 characteristic variation c.278C>T in the 6th exon of allele B, leading to the replacement of polypeptide chain p.Pro93Leu. The 3D structure simulation analysis of the protein showed that the hydrogen bonds and water molecules connected to the protein changed after amino acid substitution. The family investigation found that the grandfather, father, uncle and brother of the proband all carried the same ABO*BW.12 allele. CONCLUSION: The mutation of the 6th exon c.278C>T of ABO gene led to the substitution of polypeptide chain amino acids, which affected the stability of α-1,3-D galactosyl transferase protein, resulting in the change of enzyme activity, and the Bw.12 phenotype, which can be stably inherited.

[LRG47/EBP50 recombinant lentivirus-targeted vector vaccine enhances anti-tuberculosis immunity of RAW264.7 macrophages and its mechanism].

Objective To investigate the effect of the gene vaccine in anti-tuberculosis immunity by constructing immunity-related p47 GTPase/ezrin-radixin-moesin-binding phosphoprotein 50 (LRG47/EBP50) gene co-expression recombinant lentivirus targeting vector. Methods Recombinant lentiviral plasmid vector pLenti-EBP50-LRG47 was established by using molecular cloning and packaged as lentivirus LV-EBP50-LRG47 and H37Rv infect macrophages. Then their bactericidal ability was tested by colony-forming units while the cellular autophagy and apoptosis was detected by flow cytometry. iNOS protein was detected by Western blotting and the expression level of nitric oxide (NO) was detected by ultraviolet spectrophotometer. Results The recombinant lentivirus LV-EBP50-LRG47 successfully up-regulated the expression of EBP50 and LRG47 after infecting macrophages. Compared with the control group, LV-EBP50-LRG47 can significantly inhibit the growth of intracellular H37Rv. The autophagy and apoptosis levels of LV-EBP50-LRG47 infected macrophages increased significantly, and the expression levels of iNOS and NO were significantly up-regulated. Conclusion LRG47/EBP50 gene co-expression enhances macrophages autophagy and apoptosis, and increases generation of iNOS and NO, which significantly inhibites the growth of intracellular H37Rv.

Altered expression of Armet and Mrlp51 in the oocyte, preimplantation embryo, and brain of mice following oocyte in vitro maturation but postnatal brain development and cognitive function are normal.

Despite the efforts to recapitulate the follicle environment, oocytes from in vitro maturation (IVM) have poorer developmental potential than those matured in vivo and the effects on the resultant offspring are of concern. The aim of this study was to determine altered gene expression in oocytes following IVM and to evaluate the expression of the arginine rich, mutated in early stage of tumors gene (Armet) and mitochondrial ribosomal protein L51 (Mrpl51) in embryos and brains of fetal/postnatal mice and the brain development of IVM offspring. An IVM mouse model was established while oocytes matured in vivo were used as the controls. Suppressive subtractive hybridization (SSH) and RT-PCR/western blot were used to analyze the differential expression of genes/proteins between IVM and the control group. HE staining and water maze were used to assess the histological changes in brain tissue and cognition of the offspring. The rates of fertilization, cleavage, and live birth were significantly decreased in IVM group. Thirteen genes were upregulated in IVM oocytes compared with the control, including Armet and Mrpl51. The higher level of Armet in IVM oocytes was retained in brain of newborn mice, which could be related to the upregulation of activating transcription factor 6 (Atf6) and X-box binding protein 1 (Xbp1), while Mrpl51 was expressed normally in brain of postnatal mice. No significant differences were detected in brain weight, neuronal counts, and the cognition in the offspring between the two groups. The present results suggested that IVM could affect the pregnancy outcome and the Armet and Mrpl51 gene/protein expression. The change in Armet expression lasted while the change of Mrpl51 disappeared after birth. However, the brain development of the offspring seemed to be unaffected by IVM.

[Research progress on living quality of children conceived by assisted reproductive technology].

With the development of assisted reproductive technique (ART), children born following ART now form a sizeable subgroup of the population, so assessment for the safety of ART becomes more urgent than ever before. The health problems about living quality of children conceived by ART mainly focus on perinatal outcome and short-term follow-up study, including multiple pregnancies, low birth weight and prematurity in singleton births, congenital malformations, imprinting disorders, neurodevelopmental outcome, neonatal outcomes, physical and mental health, as well as cancer risks. In this review, we will discuss the health problems of these children, to provide data for further study.