Serum anti-Mullerian hormone predicts ovarian response in (Macaca fascicularis) monkeys
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ABSTRACT:
SUBMITTER: Long H
PROVIDER: S-EPMC6176281 | biostudies-literature | 2018 Sep
REPOSITORIES: biostudies-literature
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Serum anti-Mullerian hormone predicts ovarian response in (Macaca fascicularis) monkeys
Long Hui H Nie Yanhong Y Wang Li L Lu Yong Y Wang Yan Y Cai Yijun Y Liu Zhen Z Jia Miaomiao M Lyu Qifeng Q Qifeng Yanping Y Sun Qiang Q
Endocrine connections 20180901 9
AMH as a promising predictor of ovarian response has been studied extensively in women undergoing assisted reproductive technology treatment, but little is known about its prediction value in monkeys undergoing ovarian stimulation. In the current study, a total of 380 cynomolgus monkeys ranging from 5 to 12 years received 699 ovarian stimulation cycles. Serum samples were collected for AMH measure with enzyme-linked immunosorbent assay. It was found that serum AMH levels were positive correlated ...[more]
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Project description:Cynomolgus monkeys (Macaca fascicularis) are a valuable model organism for human disease modeling because human physiology and pathology are closer to those of cynomolgus monkeys than rodents. It has been widely reported that mature oocytes can be recovered from cynomolgus monkeys through ovarian stimulation by human follicle-stimulating hormone (hFSH). However, it is unknown whether mature oocytes can be effectively obtained through a second ovarian stimulation by hFSH. Here, we report that some ovaries (eight ovaries from 14 female monkeys) were stimulated effectively by hFSH even after the first ovum pick up, whereas the others were stimulated poorly by hFSH. Furthermore, we found antibodies against hFSH only in the serum of female monkeys with poorly stimulated ovaries. Collectively, these data suggest that anti-hFSH antibodies in serum may cause a poor ovarian response to hFSH stimulation. Finally, detection of such antibodies as well as observation of the ovary over the course of hFSH administration might be useful to predict favorable second ovarian stimulation by hFSH.
| S-EPMC6584176 | biostudies-literature
Project description:BACKGROUND: The anti-Müllerian hormone (AMH) is a dimeric protein secreted by the female ovaries and has two fundamental roles in follicle genesis. It delays the entrance of the primordial follicle into the pool of follicles in growth and diminishes the sensitivity of the ovarian follicle towards follicle-stimulating hormone (FSH). The purpose of this work was to study the AMH (nv 2.0-6.8 ng/mL) as a marker during assisted reproductive technology (ART), in order to identify cases of infertility due to polycystic ovarian syndrome (PCOS). This syndrome affects 10% of women with infertility problems, and a new biological marker could be useful to general practitioners of internal medicine to help generate the suspicion of PCOS so that they can refer the patient to the gynecologist for confirmation. METHODS: This study enrolled 236 patients aged 26-46 years undergoing assisted reproductive technology at the Institute for Maternal and Child Health, Trieste, Italy. On the third day of the ovarian cycle, the patients were given doses of AMH, FSH, and luteinizing hormone (LH, in cases of AMH < 2.0-6.8 ng/mL). A control pelvic ultrasound was also carried out. RESULTS: We identified 57 patients who were starting in vitro fertilization or embryo transfer with AMH values within the normal range (3.64 ± 1.51 ng/mL), 77 with values below normal (1.38 ± 0.32 ng/mL), and 96 cases with undetectable values of AMH. Six patients had very high AMH levels (10.0 ± 2.28 ng/mL) and, of these, five were found to have PCOS on pelvic ultrasound examination (P < 0.05). We also found inverse correlations between AMH levels and age (r = -0.52) and between AMH and FSH levels (r = -0.32). CONCLUSION: In clinical practice it is common to encounter patients who turn to medicine in search of a cure for female infertility. In our experience, AMH two or three times the normal amount (10 ± 2.28 ng/mL), is a good indication of PCOS and infertility.
| S-EPMC3219763 | biostudies-other
Project description:Angiogenesis within the ovarian follicle is an important component of ovulation. New capillary growth is initiated by the ovulatory surge of luteinizing hormone (LH), and angiogenesis is well underway at the time of follicle rupture. LH-stimulated follicular production of vascular growth factors has been shown to promote new capillary formation in the ovulatory follicle. The possibility that LH acts directly on ovarian endothelial cells to promote ovulatory angiogenesis has not been addressed. For these studies, ovaries containing ovulatory follicles were obtained from cynomolgus macaques and used for histological examination of ovarian vascular endothelial cells, and monkey ovarian microvascular endothelial cells (mOMECs) were enriched from ovulatory follicles for in vitro studies. mOMECs expressed LHCGR mRNA and protein, and immunostaining confirmed LHCGR protein in endothelial cells of ovulatory follicles in vivo. Human chorionic gonadotropin (hCG), a ligand for LHCGR, increased mOMEC proliferation, migration and capillary-like sprout formation in vitro. Treatment of mOMECs with hCG increased cAMP, a common intracellular signal generated by LHCGR activation. The cAMP analog dibutyryl cAMP increased mOMEC proliferation in the absence of hCG. Both the protein kinase A (PKA) inhibitor H89 and the phospholipase C (PLC) inhibitor U73122 blocked hCG-stimulated mOMEC proliferation, suggesting that multiple G-proteins may mediate LHCGR action. Human ovarian microvascular endothelial cells (hOMECs) enriched from ovarian aspirates obtained from healthy oocyte donors also expressed LHCGR. hOMECs also migrated and proliferated in response to hCG. Overall, these findings indicate that the LH surge may directly activate ovarian endothelial cells to stimulate angiogenesis of the ovulatory follicle.
| S-EPMC9930396 | biostudies-literature
Project description:Because of their developmental similarities to humans, nonhuman primates are often used as a model to study fetal development for potential clinical applications in humans. The detection of fetal DNA in maternal plasma or serum offers a source of fetal genetic material for prenatal diagnosis. However, no such data have been reported for cynomolgus monkeys (Macaca fascicularis), an important model in biomedical research. We have developed a specific, highly sensitive PCR system for detecting and quantifying male-specific fetal DNA in pregnant cynomolgus monkeys. We used multiplex quantitative real-time PCR to analyze cell-free DNA in maternal blood serum obtained from 46 pregnant monkeys at gestational weeks 5, 12, and 22. The presence of SRY gene and DYS14 Y chromosomal sequences was determined in 28 monkeys with male-bearing pregnancies. According to confirmation of fetal sex at birth, the probe and primers for detecting the Y chromosomal regions at each time point revealed 100% specificity of the PCR test and no false-positive or false-negative results. Increased levels of the SRY-specific sequences (mean, 4706 copies/mL serum DNA; range, 1731 to 12,625) and DYS14-specific sequences (mean, 54,814 copies/mL serum DNA; range, 4175-131,250 copies) were detected at week 22. The SRY- and DYS14-specific probes appear to be an effective combination of markers in a multiplex PCR system. To our knowledge, this report is the first to describe the detection of cell-free DNA in cynomolgus monkeys.
| S-EPMC4396932 | biostudies-literature
Project description:Background: The ability of anti-Müllerian hormone (AMH) to predict ovarian response has been studied extensively in gonadotropin-releasing hormone agonist and antagonist treatments, but no information is available regarding its value in progestin-primed ovarian stimulation (PPOS) protocol. Methods: This retrospective data analysis included 523 patients without polycystic ovary syndrome who underwent their first in vitro fertilization/intracytoplasmic sperm injection cycle with PPOS protocol at our center between Jan. 2015 and Jul. 2018. Serum AMH measurements were acquired within 12 months prior to ovarian stimulation using the automated Access AMH assay. Results: AMH exhibited a significantly positive correlation with the number of retrieved oocytes (r = 0.744, P < 0.001). For the prediction of poor (<4 oocytes) and high (>15 oocytes) response, AMH had an area under the receiver operating characteristic curve (AUC) of 0.861 and 0.773, corresponding with an optimal cutoff point of 1.26 and 4.34 ng/mL, respectively. When stratified according to the dose of medroxyprogesterone acetate (MPA) (4 mg vs. 10 mg per day), AMH retained its similarly high predictive value for poor (AUC = 0.829 and 0.886, respectively) and high response (AUC = 0.770 and 0.814, respectively) in both groups. Amongst the 314 women who received their first frozen embryo transfer (FET) following PPOS protocol, no significant differences were observed on the rates of biochemical pregnancy, clinical pregnancy, implantation, early miscarriage, multiple pregnancy and ectopic pregnancy (all P > 0.05) across AMH quartiles (≤1.43, 1.44-2.55, 2.56-4.35, >4.35 ng/mL). In a multivariable logistic regression model, age was suggested to be the only independent risk factor for clinical pregnancy (P = 0.011). Conclusions: Our data demonstrated that AMH is an adequate predictor of both high and poor ovarian response in PPOS protocol regardless of MPA dose, but it does not associate with pregnancy outcomes in the first FET cycles in a freeze-all strategy.
| S-EPMC6547790 | biostudies-literature
Project description:The Infinium Human Methylation450 BeadChip Array (Infinium 450K) is a robust and cost-efficient survey of genome-wide DNA methylation patterns. Macaca fascicularis (Cynomolgus macaque) is an important disease model; however, its genome sequence is only recently published, and few tools exist to interrogate the molecular state of Cynomolgus macaque tissues. Although the Infinium 450K is a hybridization array designed to the human genome, the relative conservation between the macaque and human genomes makes its use in macaques feasible. Here, we used the Infinium 450K array to assay DNA methylation in 11 macaque muscle biopsies. We showed that probe hybridization efficiency was related to the degree of sequence identity between the human probes and the macaque genome sequence. Approximately 61% of the Human Infinium 450K probes could be reliably mapped to the Cynomolgus macaque genome and contain a CpG site of interest. We also compared the Infinium 450K data to reduced representation bisulfite sequencing data generated on the same samples and found a high level of concordance between the two independent methodologies, which can be further improved by filtering for probe sequence identity and mismatch location. We conclude that the Infinium 450K array can be used to measure the DNA methylome of Cynomolgus macaque tissues using the provided filters. We also provide a pipeline for validation of the array in other species using a simple BLAST-based sequence identify filter.
| S-EPMC4455772 | 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:BackgroundReproductive factors, including parity, breastfeeding, and contraceptive use, affect lifetime ovulatory cycles and cumulative exposure to gonadotropins and are associated with ovarian cancer. To understand the role of ovulation-regulating hormones in the etiology of ovarian cancer, we prospectively analyzed the association of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), and inhibin B with ovarian cancer risk.MethodsOur study included 370 women from the Janus Serum Bank, including 54 type I and 82 type II invasive epithelial ovarian cancers, 49 borderline tumors, and 185 age-matched controls. We used conditional logistic regression to assess the relationship between hormones and risk of ovarian cancer overall and by subtype (types I and II).ResultsInhibin B was associated with increased risk of ovarian cancer overall [OR, 1.97; 95% confidence interval (CI), 1.14-3.39; P trend = 0.05] and with type I ovarian (OR, 3.10; 95% CI, 1.04-9.23; P trend = 0.06). FSH was not associated with ovarian cancer risk overall, but higher FSH was associated with type II ovarian cancers (OR, 2.78; 95% CI, 1.05-7.38). AMH was not associated with ovarian cancer risk.ConclusionsFSH and inhibin B may be associated with increased risk in different ovarian cancer subtypes, suggesting that gonadotropin exposure may influence risk of ovarian cancer differently across subtypes.ImpactAssociations between prospectively collected AMH, FSH, and inhibin B levels with risk of ovarian cancer provide novel insight on the influence of premenopausal markers of ovarian reserve and gonadotropin signaling. Heterogeneity of inhibin B and FSH effects in different tumor types may be informative of tumor etiology.
| S-EPMC7060092 | biostudies-literature
Project description:Animal and experimental data suggest that anti-Müllerian hormone (AMH) serves as a marker of ovarian reserve and inhibits the growth of ovarian tumors. However, few epidemiologic studies have examined the association between AMH and ovarian cancer risk. We conducted a nested case-control study of 302 ovarian cancer cases and 336 matched controls from nine cohorts. Prediagnostic blood samples of premenopausal women were assayed for AMH using a picoAMH enzyme-linked immunosorbent assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable-adjusted conditional logistic regression. AMH concentration was not associated with overall ovarian cancer risk. The multivariable-adjusted OR (95% CI), comparing the highest to the lowest quartile of AMH, was 0.99 (0.59-1.67) (Ptrend : 0.91). The association did not differ by age at blood draw or oral contraceptive use (all Pheterogeneity : ≥0.26). There also was no evidence for heterogeneity of risk for tumors defined by histologic developmental pathway, stage, and grade, and by age at diagnosis and time between blood draw and diagnosis (all Pheterogeneity : ≥0.39). In conclusion, this analysis of mostly late premenopausal women from nine cohorts does not support the hypothesized inverse association between prediagnostic circulating levels of AMH and risk of ovarian cancer.
| S-EPMC5749630 | biostudies-literature
Project description:IntroductionThe relationship between serum anti-Müllerian hormone (AMH) and the testosterone response to human chorionic gonadotropin (hCG) stimulation test is unclear.MethodsChildren who had hCG stimulation tests in one tertiary centre from 2001 to 2018 were included (n = 138). Serum testosterone was measured before (day 1 [D1]) and after 3 days (D4) of hCG stimulation. Sixty-one of these children also had prolonged hCG stimulation for 2 more weeks and serum testosterone measured after 21 days (D22). All children had a serum AMH measured on D1.ResultsOf the 138 children, D4 testosterone was normal in 104 (75%). AMH was low in 24/138 (17%) children, and 16 (67%) of these had a low D4 testosterone. Median AMH in those who had a normal vs low D4 testosterone was 850 pmol/L (24, 2280) and 54 pmol/L (0.4, 1664), respectively (P < 0.0001). An AMH > 5th centile was associated with a low D4 testosterone in 18/118 (13%; P < 0.0001). Of the 61 children who had prolonged hCG stimulation, D22 testosterone was normal in 39 (64%). AMH was low in 10/61(16%) children and 9 (90%) of these had a low D22 testosterone. Median AMH in children who responded and did not respond by D22 was 639 pmol/L (107, 2280) and 261 pmol/L (15, 1034) (P < 0.0001).ConclusionA normal AMH may provide valuable information on overall testicular function. However, a low AMH does not necessarily predict a suboptimal testosterone response to hCG stimulation.
| S-EPMC7096311 | biostudies-literature