[Association of polymorphisms in signal transducer and activator of transcription 4 gene and the susceptibility to unexplained recurrent spontaneous abortions].

OBJECTIVE: To investigate the association between the polymorphisms of signal transducer and activator of transcription 4 (STAT4) gene and the susceptibility to unexplained recurrent spontaneous abortion(URSA). METHODS: PCR-restriction fragment length polymorphism (PCR-RFLP) was used to detect genotype 3 loca (rs7574865 G/T, rs10181656 C/G and rs16833431 C/T) polymorphism of STAT4 in 246 URSA cases (URSA group) and 183 normal controls (control group) . RESULTS: (1)The frequencies of rs7574865 were genotype G/G of 36.2% (89/246) in URSA group and 46.4% (85/183) in control group, genotype G/T of 47.2% (116/246) in URSA group and 45.4% (83/183) in control group, and genotype T/T of 16.7% (41/246) in URSA group and 8.2% (15/183) in control group, which reached statistical difference (P < 0.05). The frequencies of rs10181656 were genotype CC of 36.6% (90/246) in URSA group and 46.4% (85/183) in control group, genotype C/G of 48.0% (118/246) in URSA group and 44.8% (82/183) in control group, and genotype G/G of 15.4% (38/246) in URSA group and 8.7% (16/183) in control group, which reached statistical difference (P < 0.05). The carriers of rs7574865 T allele and rs10181656 G allele increased the risk of URSA (OR = 1.51, 1.44, all P < 0.05).(2) There was no different distribution in 3 genotypes (C/C, C/T, T/T) and 2 alleles (C and T) of rs16833431 C/T between URSA patients and normal controls (P = 0.43,0.48). (3) Timated haplotype frequency distribution of rs7574865 G/T and rs10181656 C/G showed haplotype G-T conferring the susceptibility to URSA (OR = 1.49, P < 0.01), but haplotype C-G could provide protection on URSA (OR = 0.68, P < 0.01). CONCLUSION: Polymorphisms of STAT4 gene might confer the susceptibility to URSA by altering STAT4 function and (or) its expression.

Association between functional polymorphisms of Foxp3 gene and the occurrence of unexplained recurrent spontaneous abortion in a Chinese Han population.

Unexplained recurrent spontaneous abortion (URSA) is an alloimmune disease associated with the failure of fetal-maternal immunologic tolerance in which the regulatory T lymphocytes (Treg) play a pivotal role. It is well known that Forkhead box P3 (Foxp3) is a crucial regulatory factor for the development and function of Treg cells. It has also been established that deficiency of the Foxp3 gene suppresses the regulatory function of Treg cells. To determine if functional polymorphisms at the Foxp3 loci are associated with URSA in humans, we genotyped four common polymorphisms of Foxp3 gene in 146 unrelated URSA patients and 112 healthy women. The results showed that rs3761548A/C and rs2232365A/G polymorphisms were significantly associated with URSA. Additionally, we found that the allelic distribution of rs5902434 del/ATT in URSA group was slightly different from that in the control group. We conclude that functional polymorphisms of the Foxp3 gene may confer an important susceptibility to URSA in the Chinese Han population, probably by altering Foxp3 function and/or its expression.

Case Report: Primary Ovarian Leiomyoma: A Clinical Analysis of Case Series and Literature Review.

Ovarian leiomyoma accounts only for 0.5-1% of all benign ovarian tumors, and almost no preoperative diagnosis has been achieved. Commonly, these tumors are small in size and asymptomatic. However, they can become symptomatic as their size increases; thus, it is important to recognize this entity and differentiate them from ovarian malignant tumors. Radical surgeries with total hysterectomy and salpingo-oophorectomy are usually performed. However, ovary-preserving surgery has been suggested to young women, especially those desiring fertility in the future. In this study, we shared seven cases of primary ovarian leiomyomas and one inherent ligament leiomyoma, reviewed related articles to provide some new information about leiomyoma of the ovary, and discussed their proper surgical management.

Gynecological Diagnosis and Treatment of Ectopic Ureter Insertion into Vagina: Analysis of Five Cases and a Literature Review.

An ectopic ureter is a ureter that does not correctly connect to the trigone of the bladder and drains outside of the bladder. Here, we presented five cases of ectopic ureter opening into the vagina, whose clinical symptoms and malformations were rarely described in previous case reports. All five patients were hospitalized with complaints of gynecologic disease. Three of the five cases did not present the typical symptoms of urinary incontinence. Three of these cases showed congenital malformations of the female genital tract. Four cases were diagnosed in adulthood. All patients were analyzed using various imaging examinations. This study suggests that the ectopic ureter should be considered in the differential diagnosis of a pelvic mass in a patient with urinary and reproductive system abnormalities. It is essential to comprehensively evaluate complex malformations of the genitourinary system with multiple imaging tests.

[Study on association of functional polymorphisms in Foxp3 gene with the susceptibility to unexplained recurrent spontaneous abortion].

OBJECTIVE: To investigate the association between the functional polymorphisms of Foxp3 gene and unexplained recurrent spontaneous abortion (URSA). METHODS: PCR-restriction fragment length polymorphism (rs3761548, rs2294021) and PCR with sequence-specific primers (rs2232365, rs5902434) were used to detect four polymorphisms of Foxp3 in 146 URSA cases and 112 normal controls. RESULTS: (1) The frequencies of rs3761548A/C were 10.3%, 22.3% in genotype C/C, 38.4%, 40.2% in genotype A/C and 51.4%, 37.5% in genotype A/A between URSA patients and normal controls; the frequencies of rs2232365A/G were 5.5%, 15.2% in genotype A/A, 47.9%, 50.0% in genotype A/G, 46.6%, 34.8% in genotype G/G between URSA patients and normal controls; they all reached statistical difference (P < 0.05). The carriers of rs3761548A allele and rs2232365G allele increased the risk of URSA (OR = 1.73, 1.61;all P < 0.05). (2) There was no difference in the genotypic distribution of rs5902434del/ATT polymorphism between cases and controls (P = 0.10), but the frequency of del allele in URSA was statistically increased than that of controls (71.2%, 62.5%;OR = 1.49, P = 0.04). (3) There was no different distribution in 3 genotypes (C/C, T/C, T/T) and 2 alleles (T and C) of rs2294021T/C between URSA patients and normal controls (P = 0.18 and 0.08). (4) Estimated haplotype frequency distribution of rs5902434del/ATT, rs3761548A/C and rs22323565A/G showed haplotype del-A-G conferring the susceptibility to URSA (OR = 2.51, P < 0.01) but haplotype del-C-G and ATT-A-A could provide protection on URSA (OR = 0.18, 0.22; all P < 0.01). CONCLUSION: Functional polymorphisms of Foxp3 gene could probably confer the susceptibility to URSA, by altering Foxp3 function and (or) its expression.

Case Report: A Synonymous Mutation in NF1 Located at the Non-canonical Splicing Site Leading to Exon 45 Skipping.

Synonymous mutations are generally considered non-pathogenic because it did not alter the amino acids of the encoded protein. Publications of the associations between synonymous mutations and abnormal splicing have increased recently, however, not much observations available described the synonymous mutations at the non-canonical splicing sites leading to abnormal splicing. In this pedigree, the proband was diagnosed Neurofibromatosis type I due to the presence of typical cafe' au lait macules and pectus carinatum. Whole-exome sequencing identified a synonymous mutation c.6795C > T (p.N2265N) of the NF1 gene which was located at the non-canonical splicing sites. Reverse transcription polymerase chain reaction followed by Sanger sequencing was carried out, and the skipping of exon 45 was observed. Therefore, the pathogenicity of the synonymous mutation c.6795C > T was confirmed. Our finding expanded the spectrum of pathogenic mutations in Neurofibromatosis type I and provided information for genetic counseling.

Galectin-14 Promotes Trophoblast Migration and Invasion by Upregulating the Expression of MMP-9 and N-Cadherin.

Galectin-14 is specifically expressed in placental trophoblasts, and its expression is reduced in trophoblasts retrieved from the cervix of women destined to develop early pregnancy loss. However, the roles of galectin-14 in regulating trophoblasts and in the pathogenesis of pregnancy complication have never been investigated. In the current research, we aimed to investigate the roles of galectin-14 in the regulation of trophoblasts. Tissues of the placenta and villi were collected. Primary trophoblasts and human trophoblast cell line HTR-8/SVneo were used. Western blotting and RT-PCR were used to quantify gene expression. The siRNA-mediated galectin-14 knockdown and lentivirus-mediated overexpression were performed to manipulate the gene expression in trophoblasts. Transwell migration and invasion assays were used to evaluate cell migration and invasion capacity. Gelatin zymography was used to determine the gelatinase activity. Galectin-14 was significantly decreased in the villi of early pregnancy loss and the placenta of preeclampsia. Knockdown of galectin-14 in primary trophoblasts inhibited cell migration and invasion, downregulated the expression of matrix metalloproteinase (MMP)-9 and N-cadherin, the activity of MMP-9, and decreased the phosphorylation of Akt. Meanwhile, the overexpression of galectin-14 in HTR-8/SVneo promoted cell migration and invasion, upregulated the expression of MMP-9 and N-cadherin, the activity of MMP-9, and increased the phosphorylation of Akt. Increased Akt phosphorylation promoted cell migration and invasion and upregulated the expression and activity of MMP-9, while decreased Akt phosphorylation inhibited cell migration and invasion and downregulated the expression and activity of MMP-9. Thus, galectin-14 promotes trophoblast migration and invasion by enhancing the expression of MMP-9 and N-cadherin through Akt phosphorylation. The dysregulation of galectin-14 is involved in the pathogenesis of early pregnancy loss and preeclampsia.

Pro-Inflammatory Signature in Decidua of Recurrent Pregnancy Loss Regardless of Embryonic Chromosomal Abnormalities.

Recurrent pregnancy loss (RPL), especially the unexplained RPL, is associated with the disruption of maternal immune tolerance. However, little is known about the immune status at the decidua of RPL with embryonic chromosomal aberrations. Herein, mass cytometry (CyTOF) was used to interrogate the immune atlas at the decidua which was obtained from 15 RPL women-six with normal chromosome and nine with chromosomal aberrations-and five controls. The total frequency of CCR2-CD11chigh macrophages increased, while CD39high NK cells and CCR2-CD11clow macrophages decrease significantly in RPL when RPLs were stratified, compared with controls. Pro-inflammatory subsets of CD11chigh macrophages increased, while less pro-inflammatory or suppressive subsets decreased statistically in RPL decidua whenever RPLs were stratified or not. However, CD11chigh NK and CD161highCD8+ T cells increased only in RPL with normal chromosome, while the inactivated and naive CD8+/CD4+ T cells were enriched only in RPL with chromosomal aberrations. A pro-inflammatory signature is observed in RPL decidua; however, differences exist between RPL with and without chromosomal abnormalities.

Clinical analysis of 50 patients with heterotopic pregnancy after ovulation induction or embryo transfer.

OBJECTIVES: The purpose of this study was to evaluate the clinical characteristics, prenatal diagnosis, and management of patients with heterotopic pregnancy after ovulation induction or embryo transfer. METHODS: This was a retrospective study of fifty cases with heterotopic pregnancy, in which the fertilization way, type and number of embryo transferred, gestational age, clinical presentation and outcome of intrauterine, ultrasound presentation and site of ectopic pregnancy, bilateral fallopian tube and treatment were evaluated. RESULTS: Six patients had spontaneous pregnancy and two had artificial insemination after ovulation induction. Sixteen had fresh and nineteen had frozen embryo transfer with seven patients unrecorded its embryo type and number. The average days from transplantation (or intercourse/insemination) to diagnosing heterotopic pregnancy was thirty-seven with the earliest eighteen and the latest more than 70 days. Although the most common presentation was vaginal bleeding or abdominal pain, more than 21% was found by ultrasound and rare individuals even presented with gastrointestinal symptom which may imply ruptured EP and hemorrhagic shock. Giving proper treatment (surgery or local drug injection), the majority of them had a successful intrauterine pregnancy with only seven miscarried. CONCLUSIONS: Ovulation induction or embryo transfer increased the risk of HP greatly and clinician should raise high suspicious during the whole first trimester. Although the most ectopic site was ampullary, other sites such as cornual, cervical, abdominal especially interstitial or tubal stumps should also be assessed by ultrasound even in patients with bilateral salpingectomy or tubal obstructed. Repeated ultrasound tests 2 weeks after the diagnosis of intrauterine pregnancy with heart beating was very necessary to find the missed ones in suspicious patients. Compared with surgery, embryo suction with or without proper local drug injection would be more advisable for patients with cervical, cornual, or interstitial pregnancy in order to reserve the intrauterine pregnancy.

Alteration of serum adropin level in preeclampsia.

To clarify the alterations in serum adropin and preptin concentrations in preeclampsia, we determined serum adropin and preptin levels in 29 women with normal pregnancy and 32 women with preeclampsia. We found that maternal age, body mass index and fetal gender were not significantly different between two groups; however, blood pressure, gestational age and neonatal birth weight were significantly different. Serum adropin levels were significantly increased in women with preeclampsia compared with those with normal pregnancy but there were no significant differences in preptin levels. An increase in maternal serum adropin level was found in preeclampsia, and this may be a compensation for pregnancy complicated with preeclampsia.

Clinical analysis of 26 patients with histologically proven placental chorioangiomas.

OBJECTIVES: The purpose of this study was to evaluate the clinical characteristics, imaging features, pregnancy complications, prenatal management of patients with placenta chorioangioma. METHODS: This was a retrospective study of 26 cases with histologically proven placenta chorioangima, in which the natural history, pregnancy complications, and clinical characteristics including ultrasonography were evaluated. RESULTS: Twelve of the twenty-six cases had a wide range of maternal-fetal complications including polyhydramnios (7), fetal growth restriction (3), fetal distress (2), pre-eclampsia (3), fetal anemia-thrombocytopenia (2), congestive heart failure (1) and fetal abnormality (1). CONCLUSIONS: Placenta chorioangioma was associated with series of pregnancy complications such as polyhytramnios, premature delivery, maternal pre-eclampsia, fetal growth restriction, fetal distress, even fetal anemia and cardiomegaly. With regular prenatal examination, necessary treatment, and timely delivery, the majority had a good pregnancy outcome.