Abnormal Elevation of Anti-Mullerian Hormone and Androgen Levels Presenting as Granulosa Cell Tumor.
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SUBMITTER: Chi H
PROVIDER: S-EPMC8019939 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe objective of this study was to determine the gene expression profiles of the androgen/androgen receptor (AR) and anti-Müllerian hormone (AMH)/ Sry-related high-mobility group box 9 (SOX9) pathways in granulosa-luteal cells from patients undergoing standard in vitro fertilization (IVF) with or without recombinant luteinizing hormone (rLH) therapy.MethodsLevels of reproductive hormones in the pre-ovulatory follicular fluid and the expression levels of LHR (luteinizing hormone receptor), AR, SOX9, AMH, AR-associated protein 54(ARA54)and ARA70 were determined in granulosa-luteal cells by real-time reverse-transcription PCR. The effects of androgen and rLH treatments on AR and AMH expression levels were also tested in vitro using HO23 cells.ResultsWe collected 35 an 70 granulosa cell samples from patients cycled with and without rLH supplementation, respectively. The clinical outcomes were similar in patients who received rLH therapy and those who did not, though the pre-ovulatory follicular fluid levels of androstenedione, testosterone, and estradiol were significantly higher and progesterone was lower in the rLH supplementation group. Moreover, granulosa-luteal cell mRNA levels of LHR, AR, AMH, and SOX9 were significantly higher in the rLH supplementation group relative to the group that did not receive rLH supplementation. In addition, we observed significant correlations between LHR and AR mRNA expression and among AR, AMH, and SOX9 mRNA expression in granulosa-luteal cells from patients undergoing standard IVF treatment.ConclusionsIncreased expression of LHR, AR, AMH, and SOX9 is characteristic of granulosa-luteal cells from IVF/ intracytoplasmic sperm injection (ICSI) patients receiving rLH supplementation.
| S-EPMC3599510 | biostudies-literature
Project description:FMR1 premutation (55-200 CGG repeats) results in fragile X-associated primary ovarian insufficiency (FXPOI). We evaluated expression levels of folliculogenesis-related mediators, follicle-stimulating hormone (FSH) receptor and anti-Mullerian hormone (AMH), to gain insights into the mechanisms underlying the reduced ovarian function. Mural granulosa cells (MGCs) were collected from FMR1 premutation carriers and noncarriers undergoing IVF treatments. At baseline, MGCs of carriers demonstrated significantly higher mRNA expression levels of AMH (3.5 ± 2.2, n = 12 and 0.97 ± 0.5, n = 17, respectively; p = 0.0003) and FSH receptor (5.6 ± 2.8 and 2.7 ± 2.8, respectively; p = 0.02) and higher AMH protein expression on immunostaining. Accordingly, FMR1 premutation-transfected COV434 cells exhibited higher AMH protein expression than COV434 cells transfected with 20 CGG repeats. We conclude that FMR1 premutation may lead to dysregulation of AMH expression levels, probably due to a compensatory mechanism. Elucidating the pathophysiology of FXPOI may help in early detection of ovarian dysfunction and tailoring IVF treatments to FMR1 premutation carriers.
| S-EPMC8266831 | biostudies-literature
Project description:Anti-Müllerian hormone (AMH) is a member of the TGF-β superfamily secreted by the gonads of both sexes. This hormone is primarily known for its role in the regression of the Müllerian ducts in male fetuses. In females, AMH is expressed in granulosa cells of developing follicles. Like other members of the TGF-β superfamily, AMH transduces its signal through two transmembrane serine/threonine kinase receptors including a well characterized type II receptor, AMHR-II. The complete signalling pathway of AMH involving Smads proteins and the type I receptor is well known in the Müllerian duct and in Sertoli and Leydig cells but not in granulosa cells. In addition, few AMH target genes have been identified in these cells. Finally, while several co-receptors have been reported for members of the TGF-β superfamily, none have been described for AMH. Here, we have shown that none of the Bone Morphogenetic Proteins (BMPs) co-receptors, Repulsive guidance molecules (RGMs), were essential for AMH signalling. We also demonstrated that the main Smad proteins used by AMH in granulosa cells were Smad 1 and Smad 5. Like for the other AMH target cells, the most important type I receptor for AMH in these cells was BMPR-IA. Finally, we have identified a new AMH target gene, Id3, which could be involved in the effects of AMH on the differentiation of granulosa cells and its other target cells.
| S-EPMC3842941 | biostudies-literature
Project description:Female firefighters have occupational exposures which may negatively impact their reproductive health. Anti-müllerian hormone (AMH) is a clinical marker of ovarian reserve. We investigated whether AMH levels differed in female firefighters compared to non-firefighters and whether there was a dose-dependent relationship between years of firefighting and AMH levels. Female firefighters from a pre-existing cohort completed a cross-sectional survey regarding their occupational and health history and were asked to recruit a non-firefighter friend or relative. All participants provided a dried blood spot (DBS) for AMH analysis. Linear regression was used to assess the relationship between firefighting status and AMH levels. Among firefighters, the influence of firefighting-related exposures was evaluated. Firefighters (n = 106) and non-firefighters (n = 58) had similar age and BMI. Firefighters had a lower mean AMH compared to non-firefighters (2.93 ng/mL vs. 4.37 ng/mL). In multivariable adjusted models, firefighters had a 33% lower AMH value than non-firefighters (-33.38%∆ (95% CI: -54.97, -1.43)). Years of firefighting was not associated with a decrease in AMH. Firefighters in this study had lower AMH levels than non-firefighters. More research is needed to understand the mechanisms by which firefighting could reduce AMH and affect fertility.
| S-EPMC9141260 | biostudies-literature
Project description:BackgroundEndometrial proliferative lesions (EPL) usually refer to endometrial hyperplasia (EH) and endometrial cancer (EC). Among patients with premenopausal EPL who wish to preserve their fertility, only those with EH and early-stage EC have the possibility to undergo fertility preservation therapy. However, there is currently a lack of specific and reliable screening criteria and models for identifying these patients.MethodsThis study utilized a retrospective diagnostic study design. The training set included medical record information that met the criteria between August 2017 and October 2022, while the validation set consisted of medical record information that met the criteria from November 2022 to May 2023. The endometrial pathological test served as the gold standard. The serum anti-Mullerian hormone (AMH) level before endometrial sampling and a regression model were employed to predict EPL.ResultsThe study included a total of 1209 patients with PCOS (1119 in the control group and 90 in the endometrial proliferative lesion group) and 5366 women without PCOS (5249 in the control group and 117 in the proliferative lesion group). In the case of PCOS patients aged 20-39 years, the most effective screening threshold for AMH was found to be a serum AMH level of ≤5.39 ng/mL. The model used for this group was logit(p) = -2.562 - 0.430 × AMH + 0.127 × BMI + 1.512 × hypertension + 0.956 × diabetes -1.145 × regular menstruation. On the other hand, for non-PCOS women aged 20-39 years, the optimal screening threshold for AMH was determined to be a serum AMH value of ≤2.18 ng/mL. The model used for this group was logit(p) = -3.778 - 0.823 × AMH + 0.176 × BMI + 2.660 × diabetes -1.527 × regular menstruation -1.117 × dysmenorrhea. It is important to note that all of these findings have successfully passed internal verification.ConclusionFor PCOS and non-PCOS women aged 20-39 years, the serum AMH test and related multiple regression models were obtained for the warning of EPL.
| S-EPMC10650321 | biostudies-literature
Project description:PurposeThe objective of the study was to investigate whether genetic polymorphisms of the anti-Müllerian hormone (AMH) and its specific receptor anti-Müllerian hormone type II receptor (AMHRII) were associated with the hormone disorder and phenotype of polycystic ovary syndrome (PCOS).MethodsThis case-control study included 141 PCOS patients and 123 normal women. Two polymorphisms of AMH and AMHRII and the clinical characteristics of participants such as body mass index (BMI), serum luteinizing hormone (LH), estradiol levels (E2), total testosterone levels (T), and homeostasis model assessment of insulin resistance (HOMA-IR) were analyzed with the case-control sample. Gene-gene interactions of AMH and AMHRII genes were analyzed based multifactor-dimensionality reduction method.ResultsA significant difference of AMH gene polymorphisms were observed in IR-PCOS women and controls. The AMH and AMHRII gene polymorphisms were not found a significant difference in non-IR-PCOS and normal groups. To IR-PCOS women, genotypes of AMH were closely related to the serum levels of LH (P = 0.000), testosterone (P = 0.000) and HOMA-IR (P = 0.038), while in the non-IR-PCOS and normal groups, no relationship was found. No impact of AMH and AMHRII gene-gene interactions was demonstrated.ConclusionsOur research suggests that the diversity of AMH genotypes in the AMH signal pathway may be connected with the susceptibility and phenotype of PCOS with insulin resistance.
| S-EPMC4759001 | biostudies-literature
Project description:Anti-müllerian hormone (AMH) produced by granulosa cells (GCs), reserves the ovarian follicle pool for future recruitment and ovulation. However, women who have undergone cyclophosphamide (Cy) treatment have decreased AMH levels due to damaged GCs. This study establishes flow cytometry protocols for identification of GCs and investigates the cause of the Cy-induced AMH decrease by analyzing the number of GCs and their AMH production at the single cell level. Over 2 weeks, C57BL/6 mice were intraperitoneally injected 6 times with 100 mg/kg Cy and sacrificed either immediately or 4 weeks after Cy treatment. Twenty-four hours post-Cy exposure, a decrease in serum AMH levels was seen due to a reduction in the number of follicle-stimulating hormone receptor (FSHR)+ AMH+ GCs and their ability to produce AMH. However, 4 weeks after Cy treatment, serum AMH levels were still decreased due to the decreased number of FSHR+ AMH+ GCs, however, their AMH-producing ability was unaltered. Consistently, in vitro, Cy-induced low AMH production in FSHR+ AMH+ hGL5 cells (immortalized human GCs) was restored 24 h after Cy treatment, although their numbers remained decreased. Thus, the surviving GCs after Cy exposure had intact AMH-producing ability. In future, an effort to minimize GC death by Cy treatment is required, while maintaining its therapeutic effects.
| S-EPMC8451832 | biostudies-literature
Project description:BackgroundAnti-Müllerian hormone (AMH) is an important determinant of ovarian reserve in fertility workups in many clinical settings. Thus, we investigated the age dependent decline in AMH specific to the Egyptian population and sought to establish an age dependent reference interval parametrically.MethodsSerum samples were collected from 841 apparently healthy women. AMH was measured using an electro-chemiluminescent technique. Box-Cox power transformation was used to make the AMH distribution Gaussian for parametric derivation of reference intervals.ResultsPower of 0.4 was found optimal for Gaussian transformation of AMH reference values. We demonstrate the strong negative relation between circulating AMH and female age with Spearman's correlation coefficient of rS = -0.528. Age-specific reference interval was determined for every 5 years of age from 16 to 49, and nomogram was constructed by smoothing the lines connecting adjacent lower and upper reference limits.ConclusionThe age-specific reference intervals and the age-AMH nomogram could be valuable in the clinical practice of in reproductive medicine. To our knowledge, this is the first study to confirm AMH levels in Egyptian females. We were able to explore age-related AMH levels specific to Egyptian females in the fertile age group and to treat skewed AMH data in a multi-step scheme using power transformation. Thus, a more accurate nomogram was constructed accommodating a profile delineated for a wide age range and a rescaled AMH axis improving its usability.
| S-EPMC8312962 | biostudies-literature
Project description:Aims/hypothesisGiven its role in ovarian follicle development, circulating anti-Müllerian hormone (AMH) is considered to be a marker of reproductive ageing. Although accelerated reproductive ageing has been associated with a higher risk of type 2 diabetes, research on the relationship between AMH and type 2 diabetes risk is scarce. Therefore, we aimed to investigate whether age-specific AMH levels and age-related AMH trajectories are associated with type 2 diabetes risk in women.MethodsWe measured AMH in repeated plasma samples from 3293 female participants (12,460 samples in total), aged 20-59 years at recruitment, from the Doetinchem Cohort Study, a longitudinal study with follow-up visits every 5 years. We calculated age-specific AMH tertiles at baseline to account for the strong AMH-age correlation. Cox proportional hazards models adjusted for confounders were used to assess the association between baseline age-specific AMH tertiles and incident type 2 diabetes. We applied linear mixed models to compare age-related AMH trajectories for women who developed type 2 diabetes with trajectories for women who did not develop diabetes.ResultsDuring a median follow-up of 20 years, 163 women developed type 2 diabetes. Lower baseline age-specific AMH levels were associated with a higher type 2 diabetes risk (HRT2vsT3 1.24 [95% CI 0.81, 1.92]; HRT1vsT3 1.62 [95% CI 1.06, 2.48]; ptrend = 0.02). These findings seem to be supported by predicted AMH trajectories, which suggested that plasma AMH levels were lower at younger ages in women who developed type 2 diabetes compared with women who did not. The trajectories also suggested that AMH levels declined at a slower rate in women who developed type 2 diabetes, although differences in trajectories were not statistically significant.Conclusions/interpretationWe observed that lower age-specific AMH levels were associated with a higher risk of type 2 diabetes in women. Longitudinal analyses did not show clear evidence of differing AMH trajectories between women who developed type 2 diabetes compared with women who did not, possibly because these analyses were underpowered. Further research is needed to investigate whether AMH is part of the biological mechanism explaining the association between reproductive ageing and type 2 diabetes. Graphical abstract.
| S-EPMC7801305 | biostudies-literature
Project description:OBJECTIVE:To explore the association of hypothalamic-pituitary-adrenal activity with ovarian functioning in women with and without chronic abdominal pain (CAP). DESIGN AND SETTING:A secondary data analysis was performed with data from female participants in a natural history protocol at the National Institutes of Health. PARTICIPANTS:A total of 36 women (age range = 19-39 years, mean = 27.11 years) were included in the study. METHODS:This pilot study was conducted with a subset of participants enrolled in a natural history protocol conducted in the Hatfield Clinical Research Center at the National Institutes of Health. The parent study included participants with and without CAP who provided a 5-hour urine sample for determination of cortisol levels and serum samples for determination of circulating levels of cortisol, luteinizing hormone, and follicle-stimulating hormone. CAP was defined as presence or absence of chronic pain for at least 6 months and was determined via self-report. RESULTS:Anti-Müllerian hormone (AMH) concentrations declined significantly with age as expected. When AMH levels were dichotomized as normal or abnormal (defined as higher or lower than age-specific normative ranges, respectively), there were significant associations between abnormal AMH levels and CAP and urine cortisol levels. Participants with CAP or low urine cortisol levels were significantly more likely to have abnormal AMH levels. CONCLUSION:Results suggest that chronic abdominal pain and hypothalamic-pituitary-adrenal dysregulation may be associated with abnormal AMH levels.
| S-EPMC5107147 | biostudies-literature