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Aberrant maternal inflammation and oxidative stress are the two main mechanisms of pathological pregnancy. The silence information regulator (sirtuin) family is a highly conserved family of nicotinamide adenine dinucleotide (NAD)-dependent deacylases. By regulating the post-translational modification of proteins, sirtuin is involved in various biological processes including oxidative stress and inflammation. Nowadays, emerging evidence indicates that sirtuin may be closely related to the occurrence and development of pathological pregnancy. The down-regulation of sirtuin can cause spontaneous preterm delivery by promoting uterine contraction and rupture of fetal membranes, cause gestational diabetes mellitus through promoting oxidative stress and affecting the activity of key enzymes in glucose metabolism, cause preeclampsia by reducing the proliferation and invasion ability of trophoblasts, cause intrahepatic cholestasis of pregnancy by promoting the production of bile acids and T helper 1 cell (Th1) cytokines, and cause intrauterine growth restriction through inducing mitochondrial dysfunction. Moreover, the expression and activation of sirtuin can be modulated through dietary interventions, thus sirtuin is expected to become a new target for the prevention and treatment of pregnancy complications. This article reviews the role of the sirtuin family in the occurrence and development of pathological pregnancy and its influence on the development of the offspring.
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Feminino , Humanos , Gravidez , Diabetes Gestacional , Nascimento Prematuro , TrofoblastosRESUMO
In the past 20 years,molecular genetic technology has developed rapidly.The leap forward development of single-cell genetic diagnosis technologies represented by whole genome amplification combined with microarray technology or next-generation sequencing not only increased the accuracy of preimplantation genetic diagnosis (PGD) but also greatly expanded the variety and scope of detectable diseases.This paper systematically reviews the clinical application of PGD as well as recent progress of related technologies.
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Objective · To extract and identify exosomes in follicular fluid from patients with polycystic ovary syndrome in order to determine the existence of exosomes in follicular fluid, to isolate and extract miRNAs in exosomes, and to detect relative expression of miRNAs. Methods · Exosomes in follicular fluid were collected with membrane affinity chromatography and their size and morphology were observed with the transmission electron microscope. Exosome protein markers CD63 and CD81 were detected with flow cytometry. miRNAs in purified exosomes were extracted and expressions of miR-125b, miR-19b, and miR-222 were measured with TaqMan real-time PCR. Results · Exosomes in follicular fluid were circular or elliptic under the transmission electron microscope with diameters of around 30-100 nm. They had complete membrane structure and contained low density matter. Flow cytometry showed that CD63 and CD81 were positively expressed in exosomes. Real-time PCR detected expressions of miR-125b, miR-19b, and miR-222. Conclusion · Exosomes can be collected in follicular fluid from patients with polycystic ovary syndrome. Transmission electron microscopy and flow cytometry can be used to identify exosomes in follicular fluid. miR-125b, miR-19b, and miR-222 can be detected in exosomes.
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Reproduction, fat metabolism, and longevity are intertwined regulatory axes; recent studies in C. elegans have provided evidence that these processes are directly coupled. However, the mechanisms by which they are coupled and the reproductive signals modulating fat metabolism and lifespan are poorly understood. Here, we find that an oogenesis-enriched gene, c30f12.4, is specifically expressed and located in germ cells and early embryos; when the gene is knocked out, oogenesis is disrupted and brood size is decreased. In addition to the reproductive phenotype, we find that the loss of c30f12.4 alters fat metabolism, resulting in decreased fat storage and smaller lipid droplets. Meanwhile, c30f12.4 mutant worms display a shortened lifespan. Our results highlight an important role for c30f12.4 in regulating reproduction, fat homeostasis, and aging in C. elegans, which helps us to better understand the relationship between these processes.
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Animais , Feminino , Caenorhabditis elegans , Genética , Metabolismo , Proteínas de Caenorhabditis elegans , Genética , Metabolismo , Gotículas Lipídicas , Metabolismo , Metabolismo dos Lipídeos , Fisiologia , Longevidade , Fisiologia , Mutação , Oogênese , FisiologiaRESUMO
<p><b>BACKGROUND</b>Follicle stimulating hormone is necessary for normal reproduction in men. The biochemical actions of follicle stimulating hormone result from binding to the follicle stimulating hormone receptor in the plasma membrane of Sertoli cells. Here, we investigated the expression of the follicle stimulating hormone receptor in different testicular histological phenotypes of patients with idiopathic azoospermia.</p><p><b>METHODS</b>Fifty-seven cases of idiopathic azoospermia were classified into three groups according to the results of testicular biopsy: patients with hypospermatogenesis, patients with maturation arrest, and patients with Sertoli cell-only syndrome. Thirteen azoospermic patients identified by testicular biopsy as being capable of completing spermatogenesis acted as the control group. Immunohistochemistry and real-time quantitative reverse-transcriptase polymerase chain reaction were performed in each case, and the serum hormone level was also measured in all patients.</p><p><b>RESULTS</b>The serum follicle stimulating hormone level in patients with Sertoli cell-only syndrome was significantly higher than in patients with hypospermatogenesis, maturation arrest, and complete spermatogenesis (P < 0.01). The serum follicle stimulating hormone level in patients with maturation arrest was significantly higher than in patients with hypospermatogenesis and complete spermatogenesis (P < 0.05). There was no difference in serum follicle stimulating hormone levels in patients with hypospermatogenesis and complete spermatogenesis. The follicle stimulating hormone receptor expression level of testicular samples with Sertoli cell-only syndrome was significantly higher than in those with hypospermatogenesis, maturation arrest, and complete spermatogenesis (P < 0.05), but no significant difference was observed among hypospermatogenesis, maturation arrest, and complete spermatogenesis testicular samples.</p><p><b>CONCLUSIONS</b>Different serum follicle stimulating hormone levels and follicle stimulating hormone receptor expression were found in the different testicular histology phenotypes in azoospermic patients. Differential follicle stimulating hormone receptor expression in testicular tissue of patients with idiopathic azoospermia may be associated with the degree of spermatogenesis.</p>
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Adulto , Humanos , Masculino , Azoospermia , Sangue , Metabolismo , Hormônio Foliculoestimulante , Sangue , Oligospermia , Sangue , Metabolismo , Receptores do FSH , Genética , Metabolismo , Espermatogênese , Fisiologia , Testículo , MetabolismoRESUMO
Objectives To observe the genetic characteristics of chromosomes and the rates of implantation and pregnancy in couples of translocation carriers who undergo preimplantation genetic diagnosis (PGD) and to evaluate the significance of PGD in the treatment of translocation carriers. Methods Fluorescence in situ hybridization (FISH) was performed to analyze the embryos of 12 carriers of reciprocal translocation and 22 carriers of Robertsonian translocation. The results of diagnosis and the implantation and pregnancy rates were analyzed. Results A total of 253 embryos from 36 couples were retrieved and FISH was applied for the examination. The characteristics of chromosomes were diagnosed in 225 embryos and the rate of successful PGD was 88.9%. Fifty-eight embryos were found to have normal chromosome or balanced translocation and were transferred into the uterus. The rate of implantation was 36% (5/14) and 14% (6/44) and the rate of pregnancy was 4/9 and 26% (5/19) for carriers of Robertsonian translocation and reciprocal translocation, respectively. Conclusions The FISH-based PGD is effective in the diagnosis of Robertsonian translocation and reciprocal translocation of embryos. It provides the possibility of a high rate of implantation and pregnancy, and avoids recurrent abortion and unwilling termination of pregnancy.
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Objective To compare the efficacy and safety of tranexamic acid(TA)and norethisterone(NET)for the treatment of patients with ovulatory menorrhagia in China. Methods Onehundred and thirty one patients with proven ovulatory menorrhagia from gynecologic clinics of 5 teaching hospitals located in 4 different cities in China were enrolled during Jul 2004 to Dec 2006.Ameng them 128 completed the study.Patients were randomly divided into two therapeutic regimen groups:TA 1g thrice daily during menstrual cycle days(D)1-5,69 cases;or NET 5 mg twice daily on D19-26.59 cases.The drugs were administered for 2 consecutive cycles,then withdrawn and patients were followed-up for 1 more cycle.Data on menstrual blood loss [ estimated by pictorial blood assessment chart(PBAC)],length of menstrual periods,quality of life(QOL)evaluated by a 6 item health-related questionnaire were collectedbefore,during each cycle and were compared.Results Both treatments led to significant decreases of mean PBAC scores and shorter duration of menstrual periods,and improved the QOL ranking during the twotreatment cycles.The mean percentages of PBAC decrements in the TA first and second cycles were significantly greater than those in the NET corresponding cycles(35%VS 17%,P=0.004;4J4%VS 34%,P=0.04 respectively).The success rate of TA second cycle was higher than that of the NET second cycle (41%VS 24%,P=0.04).Improvement of QOL ranking in the TA first cycle was also significantly better than those in the NET first cycle ( P=0.03).The percentage of patients with at least 1 adverse event in TA group(19%)was significantly lower than that in NET group(35%,P=0.04).Patients'willingness tocontinue the treatment in the TA second and follow-up cycles(94%,79%respectively)were significantly higher than those in the corresponding cycles of NET groups(79%,59%respectively;P=0.01,P=0.02).Conclusion The regimen of TA 3 g daily during menstrual days 1-5 is a more effective and tolerable treatment than luteal phase norethisterone for patients with ovulatory menorrhagia.
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Objective To analyze the factors influencing the outcome in a frozen thawed embryo transfer (FTET)program Methods Sixty FTET cycles performed in 53 cases from September 1997 to May 2000 were analyzed retrospectively The related parameters were compared between the conceived and non conceived cycles Results One hundred and seventy eight out of 252 thawed embryos were survival Embryo transfers were undergone in 57 cycles (53 patients), resulting in 17 pregnancies (30% per transfer or 28% per thawed cycle) There were no significant difference between conceived and non conceived cycles in terms of the controlled ovarian hyperstimulation protocols, numbers of developed follicle and oocyte retrieved, fertilization rate, numbers of frozen embryo and the luteinizing hormone, estradiol, progesterone levels on human chorionic gonadotropin triggering day The percentage of good quality embryo before freezing and after thawing and survival thawed embryos were higher in conceived cycles than those in non conceived cycles (83 8% Vs 60 7%, 76 8% Vs 50 0%, 82 4% Vs 66 3%, respectively P
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0.05). Conclusions Our prospective study suggests that mode of anesthesia does not influence significantly the outcome of newborn infants delivered by elective cesarean section. It seems that both general and epidural anesthesia can be used in elective term cesarean sections safely.
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Objective To investigate insulin receptor (INSR) genotype exon 17 frequencies in women with polycystic ovary syndrome(PCOS) and to elucidate its role in the pathogenesis of PCOS. Methods The study involved 33 women with PCOS and 28 healthy control women who were genotyped for polymorphism of INSR gene exon 17 by single strand conformation polymorphism (SSCP) analysis. Body mass index (BMI), insulin sensitive index (ISI), the expression of INSR beta subunit, and serum concentration of luteinizing hormone(LH), total testosterone between the genotypes were compared. Results (1) The T -to- C mutation was observed in the INSR gene exon 17 (1008 bp). The frequency of the C/C genotype was significantly higher in patients (39%) than in the controls (11%) (P
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Objective To study prospectively the values of basal and dynamic measurement of inhibin B(INHB), estrodiol (E_2)following gonadotrophin therapy in vitro fertilization(IVF)cycles in predicting ovarian response to stimulation in young women. Methods A total of 57 patients younger than 40 years of age undergoing their first cycle of long protocol IVF treatment were studied and serum INHB, E_2 levels were detected on day 3 of the menstrual cycle, before the first administration of gonadotrophin (day 0), on days 1 and 5 after gonadotrophin therapy(day 1, day 5 ). Ovarian response was presented by: number of oocytes/total rFSH dose and square root of (number of follicles/total rFSH dose). According to number of follicles, number of oocytes and presence or absence of ovarian hyperstimulation syndrome(OHSS), we categorized the results into three different groups: poor response, normal response and OHSS. Results (1) Hormone levels on days 1,5 of rFSH stimulation: There were positive correlation between INHB (r_S:0.69-0.73), E_2 (r_S:0.60-0.73) and ovarian response (P=0.000). (2) INHB, and E_2 levels on day 5 of rFSH stimulation were significantly different between poor response, normal response and OHSS groups(P
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Objective To investigate the role of follicle stimulating hormone receptor (FSHR) expression on granulosa cells in ovarian response of women undergoing gonadotropin stimulation. Methods A total of 60 women were recruited and divided into poor, moderate and high responders according to the number of follicles. FSHR expression was detemined by Western blot on granulosa cells obtained by follicular aspiration. The peak levels of serum estradiol (E_2) were meassured by immunofluorescent assay. Results (1) The expression of FSHR was significantly different among the 3 groups, being 0.19?0.07, 0.34?0.16, and 0.45?0.18 for poor, moderate and high responders, respectively(P
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0.05). Conclusion The technique of PEP-MN-PCR from single-cell for simultaneous detection of HLA-A, B, DR types were efficient and accurate. It was possible to apply the techniques of PEP-MN-PCR to detect HLA-A, B, DR typing for preimplantational diagnosis, preliminary selection of HLA matching embryos and the patient sibling who needs cord blood stem cell transplantation.
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Objective To observe the effects of renin - angiotensin system ( RAS ) and steroid hormones onpregnancy in in vitro fertilization and embryo transfer(IVF-ET). Methods .53 tubal infertility women underwent IV F-ET under control of ovarian hyperstimulation with GnRHa/FSH/hMG/hCG. Plasma total renin, serum estradiol(E2),progesterone(P) and testosterone(T) were measured on the day of injection of injection of hCG and 36h after hCG( before getting the oocytes). ResultsPlasma total renin level on the day of hCG in pregnant group was higher than that in nonpregnant group(P<0.05), E2 and P lower than that in nonpregnant group(P<0.05, P<0.01). Plasma total renin and E2 levels 36h after hCG in pregnant group were lower than that in nonpregnant group( P<0.05). There was no difference in other hormones between the two groups. ConclusionThe high concentration of total renin on the day of hCG injection and its low concentration 36h after hCG administration are probably conducive to pregnancy.
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AIM: To study the regulatory effect two different estrogen reagents on expressions of estrogen receptor ? and ? in female rat hippocampus and cortex regions. METHODS: 12 cycles after ovariectomy, female rats were orally injected with premarin or progynova for 3 cycles before sacrificed. Semiquantitative RT-PCR was used to detect the ERs mRNA expression and SP immunohistochemistry was performed to measure the ERs protein distribution and expression. RESULTS: In premarin group, ER ? mRNA levels in both hippocampus and cortex tissues decreased significantly compared with control. ER ? protein level in hippocampus was lower than that in the control. However, ER ? protein level in cortex had no statistical difference. ER ? mRNA in the two regions and ER ? protein in cortex had no statistical differences compared with control, while ER ? protein level in hippocampus was higher than that in the control. In progynova group, both mRNA and protein levels of ER ? increased significantly in the two regions compared with the control, and ER ? mRNA level also increased in hippocampus, but ER ? mRNA level in cortex and ER ? protein levels in the above two regions showed no statistical differences. CONCLUSION: There were differential regulatory effects on ER ? and ER ? expression in female rat cognitive regions between the two different types of estrogen reagents, which may be one of the mechanisms of varied effects in different estrogen replacement therapy reagents.
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Objective To investigate whether the limited ovarian stimulation (LOS) could avoid the severe ovarian hyperstimulation syndrome (OHSS) in patients with high risk of OHSS. Methods Ten infertile patients were diagnosed as polycystic ovarian syndrome(PCOS) with high risk of OHSS. All of them were arranged LOS cycles, a long-induction protocol using gonadotropin releasing hormone agonist (GnRHa) for controlled ovarian hyperstimulation. A full dose of human chorionic gonadotropin (10 000 U) was administered when the leading follicle reached a mean diameter of 12.0-14.5 mm. Oocytes were retrieved 36 hours later, followed by conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) and embryo transfer. Results Ten patients produced 11-35 oocytes, including 4-28 oocytes of metaphase Ⅱ. Embryos were transferred in all of ten patients and eight clinical pregnancies were diagnosed. Unfortunately, ectopic pregnancy occurred in one of the patients. None of them experienced the symptoms of OHSS. Conclusions LOS may play a valuable role in preventing OHSS and achieving enough mature oocytes for the patients of PCOS. Furthermore, this protocol would not reduce the pregnancy rate of the patients.
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AIM To study the effect of estrogen on the expression of amyloid precursor protein (APP) carboxyl terminal fragment in ovariectomized female rat hippocampus and cortex regions. METHODS Ovariectomized female rats were fed with Premarin or Progynova for 3 cycles before sacrificed. S P immunohistochemistry was performed to detect the APP C terminal fragment distribution, and semi quantitative H score was used to compare the expression. RESULTS APP C terminal fragment expression in both female rat hippocampus and cortex increased significantly after ovariectomy. Compared with ovariectomized control, C terminal fragment expression in the above regions decreased. It was even lower in progynova group than in premarin group. CONCLUSION Both premarin and progynova down regulate the APP C terminal expression in ovariectomized female rat hippocampus and cortex. The modulation of progynova is more effective.
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Objective To study the effect of controlled ovarian Hyperstimulation(COH)on expression of AQP3 mRNA in mouse oocytes at metaphase Ⅱ. Methods Twenty female mice(6-7 weeks) were randomly allocated into 2 groups, mice in COH group were superovulated by intraperitoneal injection of 7.5 IU pregnant mare's serum gonadotropin(PMSG) followed by 5 IU human chorionic gonadotropin(HCG) after 46-48?h. Nothing was given to mice in control group and the estrus cycle was observed at 9?am everyday. 12-16?h following hCG injection (COH group) or at 8?am next day after the estrus (control group), mice were killed by cervical dislocation. The oviducts were excised.Cumulus masses were recovered from the dilated ampullae under a dissecting microscope,digested granulosa cells using hyaluronidase. Semi-quantitative real-time PCR of AQP3 mRNA in mouse MⅡoocytes was investigated with ?-actin as the internal control. Results Oocytes swelling assay showed that AQP3 mRNA expressed in mouse MⅡ oocytes. Using semi-quantitative real-time PCR, the expression of AQP3 mRNA was significantly decreased(P