Effect of exogenous gonadotropin on the transcriptome of human granulosa cells and follicular fluid hormone profiles

Reproductive Biology and Endocrinology

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[1] 0000 0004 0605 3760, grid.411642.4, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, 100191, Beijing, China;National Clinical Research Center for Obstetrics and Gynecology, 100191, Beijing, China;0000 0001 2256 9319, grid.11135.37, Key Laboratory of Assisted Reproduction, Ministry of Education, Peking University, 100191, Beijing, China;0000 0004 0605 3760, grid.411642.4, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, 100191, Beijing, China;National Clinical Research Center for Obstetrics and Gynecology, 100191, Beijing, China;0000 0001 2256 9319, grid.11135.37, Key Laboratory of Assisted Reproduction, Ministry of Education, Peking University, 100191, Beijing, China;0000 0001 2256 9319, grid.11135.37, Peking-Tsinghua Center of Life Sciences, Peking University, 100871, Beijing, China;0000 0004 0605 3760, grid.411642.4, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, 100191, Beijing, China;National Clinical Research Center for Obstetrics and Gynecology, 100191, Beijing, China;0000 0001 2256 9319, grid.11135.37, Key Laboratory of Assisted Reproduction, Ministry of Education, Peking University, 100191, Beijing, China;Beijing Advanced Innovation Center for Genomics, 100871, Beijing, China;0000 0004 0605 3760, grid.411642.4, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, 100191, Beijing, China;National Clinical Research Center for Obstetrics and Gynecology, 100191, Beijing, China;0000 0001 2256 9319, grid.11135.37, Key Laboratory of Assisted Reproduction, Ministry of Education, Peking University, 100191, Beijing, China;Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, 100191, Beijing, China;0000 0004 0605 3760, grid.411642.4, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, 100191, Beijing, China;National Clinical Research Center for Obstetrics and Gynecology, 100191, Beijing, China;0000 0001 2256 9319, grid.11135.37, Peking-Tsinghua Center of Life Sciences, Peking University, 100871, Beijing, China;Beijing Advanced Innovation Center for Genomics, 100871, Beijing, China;000000041936877X, grid.5386.8, Department of Obstetrics and Gynecology, New York Hospital Queens-affiliated Weill Medical College, Cornell University, 10041NY212, New York, USA;

关键词: Granulosa cells;    Transcriptome;    Follicular fluid;    Gonadotropins;    Natural cycle;   

DOI  :  10.1186/s12958-019-0489-4

来源: publisher

【 摘 要 】

BackgroundSuperovulation 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?MethodsOne 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.ResultsA 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.ConclusionsCell 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.

【 授权许可】

CC BY