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      Serum anti-Mullerian hormone predicts ovarian response in ( Macaca fascicularis) monkeys


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          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 with the number of retrieved oocytes ( P < 0.01) in the first, second and third stimulation cycles. In the first cycles, area under the curve (ROC AUC) of AMH is 0.688 for low response and 0.612 for high response respectively, indicating the significant prediction values ( P = 0.000 and P = 0.005). The optimal AMH cutoff value was 9.68 ng/mL for low ovarian response and 15.88 ng/mL for high ovarian response prediction. In the second stimulation cycles, the significance of ROC AUC of AMH for high response rather than the low response was observed ( P = 0.001 and P = 0.468). The optimal AMH cutoff value for high ovarian response was 15.61 ng/mL. In the third stimulation cycles, AMH lost the prediction value with no significant ROC AUC. Our data demonstrated that AMH, not age, is a cycle-dependent predictor for ovarian response in form of oocyte yields, which would promote the application of AMH in assisted reproductive treatment (ART) of female cynomolgus monkeys. AMH evaluation would optimize candidate selection for ART and individualize the ovarian stimulation strategies, and consequentially improve the efficiency in monkeys.

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          Serum anti-Mullerian hormone throughout the human menstrual cycle.

          The anti-Mullerian hormone (AMH) is a member of the transforming growth factor (TGF) superfamily. In women, AMH serum levels can be almost undetectable at birth, with a subtle increase noted after puberty. Data are lacking with regard to menstrual cycle day-to-day fluctuations. This longitudinal study was designed to investigate the pattern of secretion of AMH throughout the menstrual cycle in regularly cycling women. Twelve healthy female subjects aged 18-24 years participated in this study. Blood samples were taken every other day throughout one menstrual cycle. Serum FSH, LH, estradiol (E(2)), progesterone, inhibin B and AMH levels were assayed by double-antibody radioimmunoassay using commercial kits. Serum AMH in the first days of the menstrual cycle (days -14 to -12) was 3.8 +/- 1.2 ng/ml (mean +/- SD). No significant changes were observed in serum AMH levels throughout the menstrual cycle. The highest value was 3.9 +/- 1.3 ng/ml at day -12 and the lowest value was 3.4 +/- 1.1 ng/ml at day 14, and the difference was not significant. In this study, we demonstrated that serum AMH levels do not change significantly throughout the menstrual cycle. Hence, AMH exhibits a relatively stable expression during the menstrual cycle, making it an attractive determinant of ovarian activity.
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            Which follicles make the most anti-Mullerian hormone in humans? Evidence for an abrupt decline in AMH production at the time of follicle selection.

            Anti-Müllerian hormone (AMH) is exclusively produced by granulosa cells (GC) of the developing pre-antral and antral follicles, and AMH is increasingly used to assess ovarian function. It is unclear which size follicles make the most AMH (total content) and are the main contributors to circulating AMH concentrations. To determine AMH gene expression in GC (q-RT-PCR) and follicular AMH production (Elisa and RIA) in relation to follicular development, 87 follicles (3-13 mm diameter) including both GC and the corresponding follicular fluid (FF) were collected in connection with fertility preservation of human ovaries. Further, follicle number and diameter, graded in 1 mm increments, were determined by 3D ultrasound in 113 women in their natural menstrual cycle to determine follicle number and diameter in relation to circulating AMH levels. This study demonstrates for the first time a positive association between AMH gene expression in human and both total follicular fluid AMH (P < 0.02) and follicular fluid AMH concentration (P < 0.01). AMH gene expression and total AMH protein increased until a follicular diameter of 8 mm, after which a sharp decline occurred. In vivo modelling confirmed that 5-8 mm follicles make the greatest contribution to serum AMH, estimated for the first time in human to be 60% of the circulating concentration. Significant positive associations between gene expression of AMH and FSHR, AR and AMHR2 expression (P < 0.00001 for all three) and significant negative association between follicular fluid AMH concentration and CYP19a1 expression were found (P < 0.0001). Both AMH gene expression (P < 0.02) and follicular fluid concentration of AMH (P < 0.00001) correlated negatively with estradiol concentration.
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              Producing primate embryonic stem cells by somatic cell nuclear transfer.

              Derivation of embryonic stem (ES) cells genetically identical to a patient by somatic cell nuclear transfer (SCNT) holds the potential to cure or alleviate the symptoms of many degenerative diseases while circumventing concerns regarding rejection by the host immune system. However, the concept has only been achieved in the mouse, whereas inefficient reprogramming and poor embryonic development characterizes the results obtained in primates. Here, we used a modified SCNT approach to produce rhesus macaque blastocysts from adult skin fibroblasts, and successfully isolated two ES cell lines from these embryos. DNA analysis confirmed that nuclear DNA was identical to donor somatic cells and that mitochondrial DNA originated from oocytes. Both cell lines exhibited normal ES cell morphology, expressed key stem-cell markers, were transcriptionally similar to control ES cells and differentiated into multiple cell types in vitro and in vivo. Our results represent successful nuclear reprogramming of adult somatic cells into pluripotent ES cells and demonstrate proof-of-concept for therapeutic cloning in primates.

                Author and article information

                Endocr Connect
                Endocr Connect
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                September 2018
                03 August 2018
                : 7
                : 9
                : 983-989
                [1 ]Department of Assisted Reproduction Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
                [2 ]Institute of Neuroscience State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
                Author notes
                Correspondence should be addressed to Q Sun or Y Kuang or Q Lyu: qsun@ 123456ion.ac.cn or Kuangyanp@ 123456126.com or lyuqifeng@ 123456126.com

                *(H Long, Y Nie and L Wang contributed equally to this work)

                © 2018 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                : 16 July 2018
                : 03 August 2018

                anti-mullerian hormone,prediction,number of retrieved oocytes,ovarian response,cynomolgus monkeys


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