MTOR-mediated interaction between the oocyte and granulosa cells regulates the development and function of both compartments in mice†.

Coordinated development of the germline and the somatic compartments within a follicle is an essential prerequisite for creating a functionally normal oocyte. Bi-directional communication between the oocyte and the granulosa cells enables the frequent interchange of metabolites and signals that support the development and functions of both compartments. Mechanistic target of rapamycin (MTOR), a conserved serine/threonine kinase and a widely recognized integrator of signals and pathways key for cellular metabolism, proliferation, and differentiation, is emerging as a major player that regulates many facets of oocyte and follicle development. Here, we summarized our recent observations on the role of oocyte- and granulosa cell-expressed MTOR in the control of the oocyte's and granulosa cell's own development, as well as the development of one another, and provided new data that further strengthen the role of cumulus cell-expressed MTOR in synchronizing oocyte and follicle development. Inhibition of MTOR induced oocyte meiotic resumption in cultured large antral follicles, as well as cumulus expansion and the expression of cumulus expansion-related transcripts in cumulus-oocyte complexes in vitro. In vivo, the activity of MTOR in cumulus cells was diminished remarkably by 4 h after hCG administration. These results thus suggest that activation of MTOR in cumulus cells contributes to the maintenance of oocyte meiotic arrest before the LH surge. Based on the observations made by us here and previously, we propose that MTOR is an essential mediator of the bi-directional communication between the oocyte and granulosa cells that regulates the development and function of both compartments.

Oocyte-dependent activation of MTOR in cumulus cells controls the development and survival of cumulus-oocyte complexes.

Communication between oocytes and their companion somatic cells promotes the healthy development of ovarian follicles, which is crucial for producing oocytes that can be fertilized and are competent to support embryogenesis. However, how oocyte-derived signaling regulates these essential processes remains largely undefined. Here, we demonstrate that oocyte-derived paracrine factors, particularly GDF9 and GDF9-BMP15 heterodimer, promote the development and survival of cumulus-cell-oocyte complexes (COCs), partly by suppressing the expression of Ddit4l, a negative regulator of MTOR, and enabling the activation of MTOR signaling in cumulus cells. Cumulus cells expressed less Ddit4l mRNA and protein than mural granulosa cells, which is in striking contrast to the expression of phosphorylated RPS6 (a major downstream effector of MTOR). Knockdown of Ddit4l activated MTOR signaling in cumulus cells, whereas inhibition of MTOR in COCs compromised oocyte developmental competence and cumulus cell survival, with the latter likely to be attributable to specific changes in a subset of transcripts in the transcriptome of COCs. Therefore, oocyte suppression of Ddit4l expression allows for MTOR activation in cumulus cells, and this oocyte-dependent activation of MTOR signaling in cumulus cells controls the development and survival of COCs.

[Etiological analysis and individualized treatment of pharyngeal paraesthesia].

OBJECTIVE: To analyze the nosazontology of pharyngeal paraesthesia and investigate the treatment. METHOD: Two hundred and twelve misdiagnosed pharyngeal paraesthesia patients were investigated by history inquiry, routine examination, 24-hour esophageal pH monitoring, barium X-ray of the oesophagus, anxieties-athymic private measuring scale, coefficient of variation of the R-R (CVR-R), bioavailable testosterone detection (Bio-T), erection experiment and questionnaire about man climacteric syndrome. The concomitant symptoms and positions of pharyngeal paresthesia were also studied. We adopted individuallized sequential multi-therapy for every patient according to the cause of disease. RESULT: The cause of disease within 212 cases of pharyngeal paraesthesia included 62 psychic trauma, 32 endocrine system disease, 106 upper gastrointestinal disease, circulatory disease, 9 circulatory disease, 3 idiopathic. With individualized treatment, 110 cases had fully recovered, 63 cases excellence and 31 cases utility, and the efficiency rate was 96.23%. CONCLUSION: Pharyngeal paraesthesia can be caused by several factors. Thorough examination and comprehensive analysis should be applied to those incurable patient who has been treated for a long time. Short course of treatment and irrational drug use are the main causes of short-term recurrence and unsatisfactory curative effect.