Interleukin-22 improves ovulation disorder via STAT3 signalling in polycystic ovary syndrome
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PROVIDER: PRJNA1106793 | ENA |
REPOSITORIES: ENA
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Project description:Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease which leads to serious impairment of reproductive health in women of child-bearing age. Anovulation or oligo-ovulation is a common clinical manifestation of PCOS patients. The disturbance of ovarian immune microenvironment contributes to the disorders of follicle development and ovulation, and the mechanism remains unclear. Here we demonstrated the protective effect of immune factor interleukin-22 (IL-22) on PCOS follicle development and ovulation. Follicular IL-22 levels were significantly lower in PCOS patients than in the control group and were positively correlated with the oocyte fertilization rate and the high-quality embryo rate. Additionally, IL-22 evidently improved follicle development in vitro and promoted ovulation-related gene expression, which was disrupted by the depletion of interleukin-22 receptor 1 (IL-22R1) or inhibition of STAT3 in granulosa cells, indicating that IL-22 acted through IL-22R1 and STAT3 signalling pathway to promote follicle development and ovulation in PCOS. In summary, this study elucidated the vital role of ovarian immune microenvironment in follicle development and ovulation, the application of IL-22 may provide new insights into the treatment of PCOS patients.
2024-10-09 | GSE266340 | GEO
Project description:Interleukin-21 (IL-21) is a pleiotropic cytokine that induces expression of transcription factor BLIMP1 (encoded by Prdm1), which regulates plasma cell differentiation and T cell homeostasis. We identified an IL-21 response element downstream of Prdm1 that binds the transcription factors STAT3 and IRF4, which are required for optimal Prdm1 expression. Genome-wide ChIP-Seq mapping of STAT3- and IRF4-binding sites showed that most regions with IL-21-induced STAT3 binding also bound IRF4 in vivo, and furthermore, revealed that the noncanonical TTCnnnTAA GAS motif critical in Prdm1 was broadly used for STAT3 binding. Comparing genome-wide expression array data to binding sites revealed that most IL-21-regulated genes were associated with combined STAT3-IRF4 sites rather than pure STAT3 sites. Correspondingly, ChIP-Seq analysis of Irf4_/_ T cells showed greatly diminished STAT3 binding after IL-21 treatment, and Irf4_/_ mice showed impaired IL- 21-induced Tfh cell differentiation in vivo. These results reveal broad cooperative gene regulation by STAT3 and IRF4. Affymetrix expression data: Prepare CD4+ T cells from spleen. CD4+ T cells were preactivated, rested, and treated with IL-21 for 1, 6, and 24 hours. ChIP-seq data: Profiling of IRF4 and Stat3 binding with and without IL-21 stimulation in wild type and IRF4 KO mice.
2010-01-08 | E-GEOD-19198 | biostudies-arrayexpress
Project description:ContextAnti-Müllerian hormone (AMH) reduces aromatase activity and sensitivity of follicles to FSH stimulation. Therefore, elevated serum AMH may indicate a higher threshold for response to ovulation induction in women with polycystic ovary syndrome (PCOS).ObjectiveThis study sought to determine the association between AMH levels and ovulatory response to treatment among the women enrolled into the Pregnancy in PCOS II (PPCOS II) trial.Design and settingThis was a secondary analysis of data from a randomized clinical trial in academic health centers throughout the United States Participants: A total of 748 women age 18-40 years, with PCOS and measured AMH levels at baseline, were included in this study.Main outcome measuresCouples were followed for up to five treatment cycles to determine ovulation (midluteal serum progesterone > 5 ng/mL) and the dose required to achieve ovulation.ResultsA lower mean AMH and AMH per follicle was observed among women who ovulated compared with women who never achieved ovulation during the study (geometric mean AMH, 5.54 vs 7.35 ng/mL; P = .0001; geometric mean AMH per follicle, 0.14 vs 0.18; P = .01) after adjustment for age, body mass index, T, and insulin level. As AMH levels increased, the dose of ovulation induction medication needed to achieve ovulation also increased. No associations were observed between antral follicle count and ovulation.ConclusionsThese results suggest that high serum AMH is associated with a reduced response to ovulation induction among women with PCOS. Women with higher AMH levels may require higher doses of medication to achieve ovulation.
| S-EPMC5010565 | biostudies-literature
Project description:GWAS of Polycystic Ovary Syndrome Phenotypes
| PRJNA75733 | ENA
Project description:Polycystic ovary syndrome (PCOS), the most common endocrine disorder among women of reproductive age, is characterized by the coexistence of hyperandrogenism, ovulatory dysfunction, and polycystic ovaries (PCO). PCOS also represents the largest part of female oligoovulatory infertility, and the management of ovulatory and menstrual dysfunction, comprises a third of the high costs of PCOS treatment. Current pharmacological and surgical treatments for reproductive symptoms are effective, however, associated with negative side effects, such as cardiovascular complications and multiple pregnancies. For menstrual irregularities and ovulation induction in women with PCOS, acupuncture has indicated beneficial effects. This review will focus on the results from randomized controlled acupuncture trials for regulation of menstrual dysfunction and for inducing ovulation in women with PCOS although there are uncontrolled trials with nonetheless interesting results. Animal experimental studies will be further discussed when they can provide a more mechanistic explanatory view.
| S-EPMC3773899 | biostudies-literature
Project description:ObjectiveMany women with polycystic ovary syndrome (PCOS) experience infertility and hirsutism and often seek treatment for both concurrently. We investigated whether women who ovulate in response to treatment with clomiphene citrate, metformin, or both would have greater improvement in hirsutism compared with those who did not ovulate.MethodsThis is a secondary analysis evaluating the change in Ferriman-Gallwey score for the hirsute women (n=505 [80.7%]) from the Pregnancy in Polycystic Ovary Syndrome I study. This was a prospective, randomized, doubled-blind trial of 626 women with PCOS and infertility recruited from 12 university sites. They were treated with clomiphene citrate, metformin, or both (combination) for up to six cycles, and hirsutism evaluators were blinded to group assignment.ResultsThere was a significant decrease in the Ferriman-Gallwey score between baseline and completion of the study in each of the three individual groups (clomiphene citrate, P=.024; metformin, P=.005; combination, P<.001). There was no significant difference in the degree to which the hirsutism score changed when comparing the three groups (P=.44). The change in hirsutism was not associated with the duration of treatment or with the presence or absence of ovulation.ConclusionIn infertile hirsute women with PCOS, treatment with clomiphene citrate, metformin, or both for up to six cycles does not alter hirsutism.Clinical trial registrationClinicalTrials.gov, www.clinicaltrials.gov, NCT00068861.Level of evidenceII.
| S-EPMC3360417 | biostudies-literature
Project description:Interleukin-21 (IL-21) is a pleiotropic cytokine that induces expression of transcription factor BLIMP1 (encoded by Prdm1), which regulates plasma cell differentiation and T cell homeostasis. We identified an IL-21 response element downstream of Prdm1 that binds the transcription factors STAT3 and IRF4, which are required for optimal Prdm1 expression. Genome-wide ChIP-Seq mapping of STAT3- and IRF4-binding sites showed that most regions with IL-21-induced STAT3 binding also bound IRF4 in vivo, and furthermore, revealed that the noncanonical TTCnnnTAA GAS motif critical in Prdm1 was broadly used for STAT3 binding. Comparing genome-wide expression array data to binding sites revealed that most IL-21-regulated genes were associated with combined STAT3-IRF4 sites rather than pure STAT3 sites. Correspondingly, ChIP-Seq analysis of Irf4_/_ T cells showed greatly diminished STAT3 binding after IL-21 treatment, and Irf4_/_ mice showed impaired IL- 21-induced Tfh cell differentiation in vivo. These results reveal broad cooperative gene regulation by STAT3 and IRF4.
2010-01-08 | GSE19198 | GEO
Project description:Acupuncture has been demonstrated to improve menstrual frequency and to decrease circulating testosterone in women with polycystic ovary syndrome (PCOS). Our aim was to investigate whether acupuncture affects ovulation frequency and to understand the underlying mechanisms of any such effect by analyzing LH and sex steroid secretion in women with PCOS. This prospective, randomized, controlled clinical trial was conducted between June 2009 and September 2010. Thirty-two women with PCOS were randomized to receive either acupuncture with manual and low-frequency electrical stimulation or to meetings with a physical therapist twice a week for 10-13 wk. Main outcome measures were changes in LH secretion patterns from baseline to after 10-13 wk of treatment and ovulation frequency during the treatment period. Secondary outcomes were changes in the secretion of sex steroids, anti-Müllerian hormone, inhibin B, and serum cortisol. Ovulation frequency during treatment was higher in the acupuncture group than in the control group. After 10-13 wk of intervention, circulating levels of estrone, estrone sulfate, estradiol, dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, testosterone, free testosterone, dihydrotestosterone, androsterone glucuronide, androstane-3?,17?-diol-3-glucuronide, and androstane-3?,17?-diol-17-glucuronide decreased within the acupuncture group and were significantly lower than in the control group for all of these except androstenedione. We conclude that repeated acupuncture treatments resulted in higher ovulation frequency in lean/overweight women with PCOS and were more effective than just meeting with the therapist. Ovarian and adrenal sex steroid serum levels were reduced with no effect on LH secretion.
| S-EPMC4116535 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS), one of the most common endocrinal diseases among reproductive-aged women, is characterized by hyperandrogenemia, chronic oligo/anovulation and polycystic ovarian morphology. In this research, we presented microarrays to identify the differential expressed protein-coding genes and lncRNAs expression profile in the endometrium during the window of implantation between the PCOS and healthy subjects.
2019-09-13 | GSE137354 | GEO
Project description:Adolescent polycystic ovary syndrome (PCOS) is characterized by androgen excess and oligomenorrhea, and commonly driven by hepato-visceral fat excess ("central obesity") ensuing from a mismatch between prenatal and postnatal nutrition, on a background of genetic susceptibility. There is no approved treatment for adolescent PCOS. We report the pooled results of 2 pilot studies in nonobese girls with PCOS (N = 62, age 15.8 years) that compared the effects of randomized treatment for 1 year, either with an oral estro-progestogen contraceptive (OC), or with a low-dose combination of spironolactone-pioglitazone-metformin (SPIOMET, targeting the excess of ectopic fat). Auxological and endocrine-metabolic variables (including fasting insulin, androgens, high-molecular-weight adiponectin [HMW-adiponectin], and microRNA [miR]-451a), body composition (dual x-ray absorptiometry) and hepato-visceral fat (magnetic resonance imaging) were assessed on- and posttreatment. Data from menstrual diaries were combined with weekly salivary progesterone measurements to infer ovulation rates during the second and fourth quarter of the posttreatment year. OC and SPIOMET treatment reduced the androgen excess comparably, and had no differential effects on total-body lean or fat mass. However, SPIOMET was accompanied by more broadly normalizing effects, including on hepato-visceral fat and on circulating insulin, HMW-adiponectin, and miR-451a. On average, there were 3-fold more ovulations post-SPIOMET than post-OC; normovulation was only observed after SPIOMET; anovulation was >10-fold more prevalent post-OC. Pooled results of randomized studies in nonobese adolescent girls with PCOS indicate that SPIOMET treatment leads to an overall healthier, more insulin-sensitive condition-with less ectopic fat-than OC treatment, and to a more normal posttreatment ovulation rate.
| S-EPMC7182125 | biostudies-literature