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1.
Asian J Androl ; 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31571639

RESUMO

Testosterone (T) plays a crucial role in spermatogenesis because extremely low levels of intratesticular T lead to correspondingly low serum levels of total T (tT), severe disorders of spermatogenesis, and male sterility. However, there is little consensus on the lower limits of serum tT in proven fertile men undergoing assisted reproductive technology treatments in Chinese or other Asian populations. We aimed to establish the reference range of serum tT based on a population of 868 fertile Chinese men undergoing in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) treatments. We defined a fertile man as having had a live baby with his partner as recorded in our IVF registration system. The lower limits of serum tT were established using a Siemens IMMULITE 2000 chemiluminescent system. The 1st, 2.5th, and 5th percentiles and their 95% confidence intervals (CIs) were 3.6 (95% CI: 2.7-4.1) nmol l-1, 4.3 (95% CI: 4.1-5.0) nmol l-1, and 5.6 (95% CI: 4.8-5.8) nmol l-1, respectively. Using the linear correlation of serum tT between the Siemens platform and a liquid chromatography-tandem mass spectrometry platform, the calculated lower limits of serum tT were also established for fertile Chinese men undergoing IVF/ICSI-ET treatments, which will benefit the clinical diagnosis and treatment of male infertility during such procedures.

2.
Am J Hum Genet ; 105(4): 803-812, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31564438

RESUMO

Concurrent hearing and genetic screening of newborns is expected to play important roles not only in early detection and diagnosis of congenital deafness, which triggers intervention, but also in predicting late-onset and progressive hearing loss and identifying individuals who are at risk of drug-induced HL. Concurrent hearing and genetic screening in the whole newborn population in Beijing was launched in January 2012. This study included 180,469 infants born in Beijing between April 2013 and March 2014, with last follow-up on February 24, 2018. Hearing screening was performed using transiently evoked otoacoustic emission (TEOAE) and automated auditory brainstem response (AABR). For genetic testing, dried blood spots were collected and nine variants in four genes, GJB2, SLC26A4, mtDNA 12S rRNA, and GJB3, were screened using a DNA microarray platform. Of the 180,469 infants, 1,915 (1.061%) were referred bilaterally or unilaterally for hearing screening; 8,136 (4.508%) were positive for genetic screening (heterozygote, homozygote, or compound heterozygote and mtDNA homoplasmy or heteroplasmy), among whom 7,896 (4.375%) passed hearing screening. Forty (0.022%) infants carried two variants in GJB2 or SLC26A4 (homozygote or compound heterozygote) and 10 of those infants passed newborn hearing screening. In total, 409 (0.227%) infants carried the mtDNA 12S rRNA variant (m.1555A>G or m.1494C>T), and 405 of them passed newborn hearing screening. In this cohort study, 25% of infants with pathogenic combinations of GJB2 or SLC26A4 variants and 99% of infants with an m.1555A>G or m.1494C>T variant passed routine newborn hearing screening, indicating that concurrent screening provides a more comprehensive approach for management of congenital deafness and prevention of ototoxicity.

3.
BMJ Open ; 9(9): e030366, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31575574

RESUMO

INTRODUCTION: Intracytoplasmic sperm injection (ICSI), originally introduced as add-on to in vitro fertilisation (IVF) for couples with severe male infertility, is in current clinical practice also used in couples with mild male or even unexplained infertility. However, ICSI has involved unresolved concerns regarding the selection and damage to gametes and the health conditions of the offspring, and it is also labour intensive and therefore more expensive than conventional IVF. High-quality well-powered randomised clinical trials (RCTs) comparing ICSI and IVF are lacking. METHODS AND ANALYSIS: We propose a multicentre, open-label RCT in 10 reproductive medical centres across China. We will study couples with non-severe male infertility (defined as a semen concentrate 5-15×106/mL or sperm with a progressive motility 10%-32%) scheduled for their first or second ICSI or IVF cycle, as low fertility rate after fertilisation are more frequent in this population, which could lead to controversy about ICSI or conventional IVF for fertilisation. On the day of oocyte retrieval, eligible participants are after informed consent be randomised to undergo either ICSI or conventional IVF in a 1:1 treatment ratio. Other standard assisted reproductive treatments are similar and parallel between two groups. Our primary outcome is ongoing pregnancy leading to live birth after the first cycle with embryo transfer. To demonstrate or refute a difference of 7% between ICSI and conventional IVF, we need to include 2346 women (1173 in each intervention arm). In addition, we will follow-up neonatal outcomes after delivery to identify the influence of ICSI on offspring. ETHICS AND DISSEMINATION: Ethical approval was obtained from Peking University Third Hospital medical science research ethics committee. The findings will be disseminated to the public through conference presentations and peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov registry (NCT03298633).

5.
Nat Med ; 25(9): 1327, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31501595
6.
Artigo em Inglês | MEDLINE | ID: mdl-31514246

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is complex with reproductive, metabolic and psychological features. Infertility is a prevalent presenting feature of PCOS with approximately 75% of these women suffering infertility due to anovulation, making PCOS by far the most common cause of anovulatory infertility. Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated. AIMS: This review paper aims to provide a brief update on the best available and most current research evidence supporting the treatment of PCOS which informed the recommendations in the assessment and treatment of infertility section of the international evidence-based guideline on PCOS 2018. MATERIALS AND METHODS: International evidence-based guideline development engaged professional societies and consumer organisations with multidisciplinary experts and women with PCOS directly involved at all stages. RESULTS: Lifestyle change alone is considered the first-line treatment for the management of infertile anovulatory PCOS women who are overweight or obese. Letrozole should now be considered first-line pharmacological treatment for ovulation induction to improve fertility outcomes. Clomiphene citrate alone and metformin alone could also be used as first-line pharmacological therapy, although both are less effective than letrozole and metformin is less effective than clomiphene citrate in obese women. Gonadotrophins or laparoscopic ovarian surgery are usually second-line ovulation induction therapies. In the absence of an absolute indication for in vitro fertilisation (IVF) / intracytoplasmic sperm injection, women with PCOS and anovulatory infertility could be offered IVF as third-line therapy where first- or second-line ovulation induction therapies have failed. CONCLUSION: This review provides the best available evidence informing recommendations (along with clinical expertise and consumer preference) which provide clinicians with clear advice on best practice for the management of infertile women with PCOS.

7.
Mol Genet Genomic Med ; 7(10): e00906, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31429517

RESUMO

BACKGROUND: Mutations of human androgen receptor (AR) gene are responsible for androgen insensitivity syndrome (AIS). Variable phenotypes and androgen receptor binding activity have permitted the classification of AIS into complete (CAIS), partial (PAIS), and minimal or mild (MAIS) forms. Somatic mosaicism in AIS is a rare condition which happened when de novo mutations occur after the zygotic stage. METHODS: Clinical evaluation, hormone measurements, and molecular analysis were performed to diagnose the patient in the study. RESULTS: A 46, XY girl who conceived through in vitro fertilization (IVF), presented with partial virilization of external genitalia, was found to have the p.C620R in heterozygosity. The variant p.C620R of AR has been previously reported in a patient with completely feminized external genitalia, which was inherited from the heterozygote carrier mother. Mutation analysis of the mother of our patient revealed that the variant was de novo and presented as a somatic mosaicism which indicated an insufficient amount of wild-type AR in our patient. CONCLUSION: This is the first case that AIS was caused by de novo mutation of AR in a 46, XY Disorder of Sexual Development (DSD) patient by the assisted reproduction technique (ART). The phenotype of partial virilization could be explained by AR mutation in somatic mosaicism.

8.
BMJ ; 366: l4680, 2019 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-31434652

RESUMO

OBJECTIVE: To measure the association of China's universal two child policy, announced in October 2015, with changes in births and health related birth characteristics. DESIGN: National, descriptive before-and-after comparative study. SETTING: Every county in 28 of 31 provinces of mainland China. PARTICIPANTS: Births included in two national databases: 67 786 749 births from county level monthly aggregated data between January 2014 and December 2017; and 31 786 279 deliveries from individual level delivery information records between January 2015 and December 2017. MAIN OUTCOME MEASURES: Monthly mean number of births and mean proportion of multiparous mothers and mothers aged 35 and over, preterm deliveries, and caesarean deliveries. RESULTS: The study had two phases: the baseline period (up to and including June 2016, nine months after the policy announcement) and the effective period (from July 2016 to December 2017). The estimated number of additional births attributable to the new policy between July 2016 and December 2017 was 5.40 million (95% confidence interval 4.34 to 6.46). The monthly mean percentage of multiparous mothers and mothers aged 35 and over increased by 9.1 percentage points (95% confidence interval 6.4 to 11.7) and 5.8 percentage points (5.2 to 6.4), respectively. This increase in older mothers, however, was not associated with a concurrent increase in the overall rate of preterm birth. The monthly mean caesarean delivery rate among multiparous mothers increased by 1.2 percentage points (0.8 to 1.6) from 39.7% to 40.9%, and decreased by 3.0 percentage points (-3.5 to -2.5) among nulliparous mothers from 39.6% to 36.6%. CONCLUSIONS: Since its announcement in October 2015, the universal two child policy has been associated with a rise in births in China and with changes in health related birth characteristics: women giving birth have been more likely to be multiparous, and more likely to be aged 35 and over. No evidence of concurrent worsening outcomes (that is, premature births) was seen.


Assuntos
Coeficiente de Natalidade/tendências , Política de Planejamento Familiar/tendências , Adulto , China/epidemiologia , Características da Família , Feminino , Humanos , Recém-Nascido , Masculino , Idade Materna , Paridade , Gravidez , Nascimento Prematuro/epidemiologia
9.
Nature ; 572(7771): 660-664, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31435013

RESUMO

Implantation is a milestone event during mammalian embryogenesis. Implantation failure is a considerable cause of early pregnancy loss in humans1. Owing to the difficulty of obtaining human embryos early after implantation in vivo, it remains unclear how the gene regulatory network and epigenetic mechanisms control the implantation process. Here, by combining an in vitro culture system for the development human embryos after implantation and single-cell multi-omics sequencing technologies, more than 8,000 individual cells from 65 human peri-implantation embryos were systematically analysed. Unsupervised dimensionality reduction and clustering algorithms of the transcriptome data show stepwise implantation routes for the epiblast, primitive endoderm and trophectoderm lineages, suggesting robust preparation for the proper establishment of a mother-to-offspring connection during implantation. Female embryos showed initiation of random X chromosome inactivation based on analysis of parental allele-specific expression of X-chromosome-linked genes during implantation. Notably, using single-cell triple omics sequencing analysis, the re-methylation of the genome in cells from the primitive endoderm lineage was shown to be much slower than in cells of both epiblast and trophectoderm lineages during the implantation process, which indicates that there are distinct re-establishment features in the DNA methylome of the epiblast and primitive endoderm-even though both lineages are derived from the inner cell mass. Collectively, our work provides insights into the complex molecular mechanisms that regulate the implantation of human embryos, and helps to advance future efforts to understanding early embryonic development and reproductive medicine.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31393569

RESUMO

CONTEXT: The luteinizing hormone/chorionic gonadotropin receptor (LHCGR) is mainly expressed in gonads and plays important roles in estradiol production, ovulation and luteal formation. Women with pathogenic LHCGR variants suffer from infertility, and successful fertility treatments for such women have never been reported. OBJECTIVE: The purpose of this study was to determine whether women with pathogenic LHCGR variants can achieve successful pregnancies through in vitro fertilization (IVF). METHOD: Three women with luteinizing hormone (LH) resistance and infertility and their parents underwent exome sequencing. The biochemical characteristics and functional effects of LHCGR mutation were assessed in transfected HEK-293T cells and primary granulosa cells. RESULTS: All affected women harbored pathogenic LHCGR variants. The LHCGR variants lacked cell surface localization and signal transduction abilities in vitro and in vivo. After dual triggering and prolonging the interval between triggering and oocyte pick-up (OPU), all 3 patients achieved oocytes and high-quality embryos. After frozen embryo transfer, one woman successfully birthed twins, and one woman successfully birthed a live boy. Apart from difficulties in oocyte retrieval, no obvious abnormalities in fertilization or during embryo development and pregnancy were identified in these patients. CONCLUSIONS: This study is the first to report successful assisted reproductive treatment for women with pathogenic LHCGR variants using their own oocytes. Our results supported that defects in LHCGR disrupt ovulation but have no effect on fertilization and embryo development.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31396885

RESUMO

Because elevated levels of caffeine intake can cause many health complications, it is necessary to develop an accurate, simple, rapid, and cost-effective methodology to quantify caffeine in commonly consumed products. This article discusses electrochemical methods to synthesize platinum-graphene hybrid nanosheets (Pt-GR), and how these methods can be utilized to create a new modified electrode, the platinum-graphene nanohybrid glass carbon electrode (Pt-GR/GCE). The electrochemical behavior of caffeine on Pt-GR/GCE was studied by differential pulse voltammetry (DPV). The results showed that a sensitive oxidation peak was observed at 1.336 V in 0.01 mol L-1 H2SO4 buffer solution, indicating that the Pt-GR/GCE exhibited a good electrooxidation activity towards caffeine. The detection limit is 1.129 × 10-7 mol L-1. The modified electrode was applied to the determination of caffeine in real samples with satisfactory electrocatalytic results.

12.
Medicine (Baltimore) ; 98(34): e16904, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441870

RESUMO

Aim of this study was to determine if surface electromyography (sEMG) could provide objective data in monitoring the alteration of signal amplitude of myoelectric activity of the paraspinal muscles in the patients with acute nonspecific lower back pain (ANLBP), and to explore the correlation between sEMG data and symptom relief in the ANLBP patients before and after massage therapy.Forty-five ANLBP patients and 20 healthy subjects were enrolled into this study. Patients were given massage therapy for 1 week. The average electromyography (AEMG), visual analogue scale (VAS), and distance of finger to floor (DFTF) were measured before and after treatment.AEMG at flexion and maintained flexion positions were significantly higher in the ANLBP group compared to that in the control group. At extension position, in contrast, AEMG was significantly lower in the ANLBP patients than that of control group, and there was no significant difference between the 2 groups at upright position. After massage therapy for the ANLBP patients, AEMG was significantly reduced at flexion and maintained flexion positions, but significantly increased at extension position than that before treatment. VAS and DFTF were also significantly reduced after treatment. In addition, AEMG alteration at maintained flexion position was significantly correlated with improvement of VAS or DFTF.Myoelectric activity of the paraspinal muscles in the ANLBP patients was different from that of healthy subjects. Massage therapy not only relived patients' symptoms, but also normalized myoelectric activity of the paraspinal muscles in the ANLBP patients.


Assuntos
Eletromiografia/métodos , Dor Lombar/terapia , Massagem/métodos , Músculos Paraespinais/fisiopatologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Amplitude de Movimento Articular/fisiologia , Resultado do Tratamento
13.
PLoS Biol ; 17(7): e3000365, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31269016

RESUMO

The developmental pathway of the neural retina (NR) and retinal pigment epithelium (RPE) has been revealed by extensive research in mice. However, the molecular mechanisms underlying the development of the human NR and RPE, as well as the interactions between these two tissues, have not been well defined. Here, we analyzed 2,421 individual cells from human fetal NR and RPE using single-cell RNA sequencing (RNA-seq) technique and revealed the tightly regulated spatiotemporal gene expression network of human retinal cells. We identified major cell classes of human fetal retina and potential crucial transcription factors for each cell class. We dissected the dynamic expression patterns of visual cycle- and ligand-receptor interaction-related genes in the RPE and NR. Moreover, we provided a map of disease-related genes for human fetal retinal cells and highlighted the importance of retinal progenitor cells as potential targets of inherited retinal diseases. Our findings captured the key in vivo features of the development of the human NR and RPE and offered insightful clues for further functional studies.

14.
Nat Med ; 25(8): 1225-1233, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31332392

RESUMO

Polycystic ovary syndrome (PCOS) is characterized by androgen excess, ovulatory dysfunction and polycystic ovaries1, and is often accompanied by insulin resistance2. The mechanism of ovulatory dysfunction and insulin resistance in PCOS remains elusive, thus limiting the development of therapeutics. Improved metabolic health is associated with a relatively high microbiota gene content and increased microbial diversity3,4. This study aimed to investigate the impact of the gut microbiota and its metabolites on the regulation of PCOS-associated ovarian dysfunction and insulin resistance. Here, we report that Bacteroides vulgatus was markedly elevated in the gut microbiota of individuals with PCOS, accompanied by reduced glycodeoxycholic acid and tauroursodeoxycholic acid levels. Transplantation of fecal microbiota from women with PCOS or B. vulgatus-colonized recipient mice resulted in increased disruption of ovarian functions, insulin resistance, altered bile acid metabolism, reduced interleukin-22 secretion and infertility. Mechanistically, glycodeoxycholic acid induced intestinal group 3 innate lymphoid cell IL-22 secretion through GATA binding protein 3, and IL-22 in turn improved the PCOS phenotype. This finding is consistent with the reduced levels of IL-22 in individuals with PCOS. This study suggests that modifying the gut microbiota, altering bile acid metabolism and/or increasing IL-22 levels may be of value for the treatment of PCOS.

15.
Cell Death Dis ; 10(8): 558, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31332164

RESUMO

Natriuretic peptide type C (NPPC) secreted by mural granulosa cells (MGCs) maintains oocyte meiotic arrest via the activation of guanylyl cyclase-linked natriuretic peptide receptor 2 (NPR2). Here, we investigated the effect of transforming growth factor (TGF)-ß on NPPC expression in MGCs and oocyte maturation. TGF-ß ligands (TGFB1 and TGFB3, but not TGFB2) and receptors (TGFBR1 and TGFBR2) were predominantly expressed in MGCs. The activation of the follicle-stimulating hormone (FSH) receptor by FSH/equine chorionic gonadotropin (eCG) increased the levels of TGFB1, TGFBR2, and TGF-ß downstream SMAD proteins in MGCs, which were decreased following the activation of the luteinizing hormone (LH) receptor by human chorionic gonadotropin (hCG). TGF-ß significantly increased the gene and protein levels of NPPC in cultured MGCs through SMAD3 binding to Nppc promoter regions. In the presence of FSH, TGF-ß further increased NPPC levels and inhibited oocyte meiotic resumption of cumulus-oocyte complexes (COCs). Moreover, Tgfbr2-specific depletion in granulosa cells using Fshr-Cre mice reduced NPPC mRNA and protein levels, resulting in the weak maintenance of oocyte meiotic arrest within large antral follicles. Tgfbr2 depletion also impaired follicle development, ovulation, and female fertility. Taken together, TGF-ß-promoted NPPC in MGCs is involved in maintaining oocyte meiotic arrest. FSH and LH could regulate NPPC levels in MGCs via TGF-ß and then control the process of oocyte meiosis.

17.
Reprod Biomed Online ; 39(2): 199-204, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31160240

RESUMO

RESEARCH QUESTION: Does artificial oocyte activation improve clinical outcomes for patients at risk of intracytoplasmic sperm injection (ICSI) fertilization failure? DESIGN: In this study, sibling oocytes from patients with previous ICSI failure or severe teratozoospermia were divided equally into two groups, half for artificial oocyte activation (AOA) with ionomycin after conventional ICSI and the other half for conventional ICSI only (non-AOA). The fertilization rates, cleavage rates, transferable embryo rates and blastulation rates of the two groups were compared first; the clinical pregnancy and live birth rates were also compared to assess the efficiency and safety of AOA. RESULT: The outcomes of the AOA group were significantly better than those of the conventional ICSI group in terms of the fertilization (50.38% versus 33.86%, respectively, P < 0.001), cleavage (59.16% versus 39.04%, respectively, P < 0.001) and transferable embryo rates (43.51% versus 26.69%, respectively, P < 0.001). The blastulation (43.53% versus 36.11%, respectively), implantation (26.83% versus 15.79%, respectively), clinical pregnancy (38.46% versus 25%, respectively) and live birth rates (38.46% versus 16.67%, respectively) were not significantly different. CONCLUSION: This study showed that AOA improved some aspects of cycles at risk of ICSI failure by increasing the fertilization and transferable embryo rates. But blastulation, pregnancy and implantation rates were not improved. The study is limited by its small size and absence of data on cumulative outcomes.

18.
Sci China Life Sci ; 62(7): 886-894, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31152388

RESUMO

Birth defects are caused by multiple factors, such as chromosome abnormality, environmental factors, and maternal factors. In this study, we focused on exploring the genetic causes of a non-consanguineous couple who suffered from four times of unsuccessful pregnancy due to unexplained recurrent fetal malformations with similar symptoms and normal chromosome copy number variations. Using trio-whole exome sequencing (trio-WES) for this couple and one of the affected fetuses, we found a mutation, c.1996delC on the maternal imprinted gene MAGEL2 that was carried by the affected fetus and husband, leading to Schaaf-Yang syndrome. To screen this mutation, we further performed preimplantation genetic diagnosis (PGD) strategy followed by a gene pedigree validation and pathogenicity analysis. After the transfer of a PGD-screened embryo, a normal newborn without previous abnormal symptoms was born (February 15, 2019). We present the first data that identified a pathogenic gene (MAGEL2 c.1996delC) in a fetus with Schaaf-Yang syndrome in the EAS (East Asian) database and overcame this genetic defect by using processed PGD for this couple based on the WES results.

19.
Sci China Life Sci ; 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31197760

RESUMO

A decrease in cancer deaths has resulted in the possibility of child bearing for many young adult cancer survivors. Most antitumor treatment modalities are detrimental to female fertility, and methods for fertility preservation before gonadotoxic treatment, including cryopreservation of oocytes, embryos and ovarian tissue, have therefore been developed. This review focuses on the ovarian function of cancer patients, the safety and efficacy of fertility preservation methods, and the pregnancy outcomes of these patients. Breast cancer and hematological tumors constitute the majority of cancers in reproductive-aged female oncology patients. Ovarian function may not be impacted by breast cancer cells, while in patients with hematological malignancies, decreases in anti-Müllerian hormone and antral follicle counts have been demonstrated. In most cases, patients can undergo ovarian stimulation without delaying treatment, and a new stimulation protocol known as dual stimulation, which may be more efficient, has now been developed. Birth outcomes are also acceptable in cancer patients.

20.
Reprod Biol Endocrinol ; 17(1): 49, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31234873

RESUMO

BACKGROUND: Superovulation treatment had some adverse effects on maturity and development of oocytes. Can superovulation dose of gonadotropins (Gns) affect the transcriptome of granulosa cells and follicular fluid (FF) hormone levels? METHODS: One leading pre-ovulatory follicle per subject was used from three natural-cycle and four Gn-stimulated patients. Granulosa cells and FF samples were collected from the same leading follicle of each patient. RNA was extracted from granulosa cells and subjected to deep sequencing and analysis. Follicle-stimulating hormone (FSH), estradiol (E2), androstenedione (AND), testosterone (T), luteinizing hormone (LH), and progesterone (P4) levels in FF were measured by immunoassays. Student's t test was used for statistical analysis. RESULTS: A total of 715 genes were up-regulated, and 287 genes were down-regulated, in the Gn-stimulated group relative to the control group. Gene Ontology analysis revealed that the down-regulated genes were enriched in cell cycle and meiosis pathways, primarily those associated with follicle or oocyte maturation and quality. On the other hand, the up-regulated genes were enriched in functions related to immunity and cytokine-cytokine receptor interactions. Compared to the follicles of natural cycle, the E2 and LH concentrations were significantly reduced (P < 0.001), the P4 concentration was significantly increased (P = 0.003), and the concentrations of FSH, T and AND had no difference in the follicles of Gn-stimulated cycle. CONCLUSIONS: Cell cycle- and meiosis-associated genes were down-regulated by Gns stimulation, whereas immune- and cytokine-associated genes were up-regulated. Hormone levels were also affected by Gns stimulation. Compared with natural-cycle follicles,putative markers associated with oocyte quality and follicle maturation were significantly different from those in Gn-stimulated follicles. Hormone levels in follicles were compatible with the steroidogenic patterns of granulosa cell, which reflects the follicle maturation and oocyte quality.

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