Tyrosine phosphatase SHP2 in ovarian granulosa cells balances follicular development by inhibiting PI3K/AKT signaling

In mammals,the growth and maturation of oocytes within growing follicles largely depends on ovarian granulosa cells(GCs)in response to gonadotropin stimulation.Many signals have been shown to regulate GC proliferation and apoptosis.However,whether the tyrosine phosphatase SHP2 is involved remains unclear.In this study,we identified the crucial roles of SHP2 in modulating GC proliferation and apoptosis.The production of both mature oocytes and pups was increased in mice with Shp2 specifically deleted in ovarian GCs via Fshr-Cre.Shp2 deletion simultaneously promoted GC proliferation and inhibited GC apoptosis.Furthermore,Shp2 deficiency promoted,while Shp2 overexpression inhibited,the proliferation of cultured primary mouse ovarian GCs and the human ovarian granulosa-like tumor cell line KGN in vitro.Shp2 deficiency promoted follicule-stimulating hormone(FSH)-activated phosphorylation of AKT in vivo.SHP2 deficiency reversed the inhibitory effect of hydrogen peroxide(H_(2)O_(2))on AKT activation in KGN cells.H_(2)O_(2) treatment promoted the interaction between SHP2 and the p85 subunit of PI3K in KGN cells.Therefore,SHP2 in GCs may act as a negative modulator to balance follicular development by suppressing PI3K/AKT signaling.The novel function of SHP2 in modulating proliferation and apoptosis of GCs provides a potential therapeutic target for the clinical treatment of follicle developmental dysfunction.

Reproduction does not impede the stopover departure to ensure a potent migration in Cnaphalocrocis medinalis moths

Despite the importance of reproduction in insects,its relation with multi-stop flight remains poorly understood in migratory species.To clarify whether reproductive maturation commences during the multi-stop flight or after the completion of migration,we conducted physiological and behavioral assays in the rice leaf roller Cnaphalocrocis medinalis with laboratory-simulated conditions and field-captured populations.We found that the ovarian development was significantly promoted by tethered flight treatment for 1-2 nights when compared to the unflown group,while the flight muscle development was not impaired.There was no significant difference in flight duration,flight distance and flight velocity between mated and virgin female moths,indicating that mated moths remained competent for the subsequent flights as did the virgins.Using an integrated field assay,we identified that over 60%of the female moths in the migrating populations cap-tured by high-altitude searchlights in the Immigration period of a season had completed the ovarian development and mating.Sexually mature and mated moths collected in the rice field in the Emigration period were found capable of engaging in migratory take-off,as observed using an indoor monitoring platform.Overall,our findings point out that C.med-inalis managed to complete reproductive maturation to a large extent during the multi-stop migratory flight without compromising the migration performance.Such a cost-effective strategy ensures a successful migration for the moths.These findings advance our under-standing of the relationship between reproduction and migration,thus shedding light on the development of novel control measures for the outbreak of migratory insect pests.

Follicles were reconstituted from dissociated mouse fetal ovarian cells in vitro

Early folliculogenesis involved in the interaction of germ cells and somatic cells is a complicated physiological event. Female germ cells are committed to differentiate into oocytes and finish complete development in the functional units of follicles. Thus there will be great significance in basal research and practices to evaluate the possibility of ovarian cells to reconstitute into follicles in vitro. In the present research, 12-16 dpc (days post coitum) mouse fetal ovarian cells were respectively isolated using collagenase digestion and cultured in droplets in vitro. The results revealed that the fetal ovarian cells of 12-16 dpc appeared to form multiple cell aggregates and tissue-like pieces in vitro. However, 12-13 dpc ovarian cells failed to form the follicles. 14-15 dpc ovarian cells were competent to form a few follicle-like complexes. Furthermore many small typical follicles were reconstituted from 16 dpc ovarian cells in vitro. The results showed for the first time that mouse embryonic

Deletion of Gab2 in mice protects against hepatic steatosis and steatohepatitis:a novel therapeutic target for fatty liver disease

Fatty liver disease is a serious health problem worldwide and is the most common cause for chronic liver disease and metabolic disorders.The major challenge in the prevention and intervention of this disease is the incomplete understanding of the underlying mechanism and thus lack of potent therapeutic targets due to multifaceted and interdependent disease factors.In this study,we investigated the role of a signaling adaptor protein,GRB2-associated-binding protein 2(Gab2),in fatty liver using an animal disease model.Gab2 expression in hepatocytes responded to various disease factor stimulations,and Gab2 knockout mice exhibited resistance to fat-induced obesity,fat-or alcohol-stimulated hepatic steatosis,as well as methionine and choline deficiency-induced steatohepatitis.Concordantly,the forced expression or knockdown of Gab2 enhanced or diminished oleic acid(OA)-or ethanol-induced lipid production in hepatocytes in vitro,respectively.During lipid accumulation in hepatocytes,both fat and alcohol induced the recruitment of PI3K or Socs3 by Gab2 and the activation of their downstream signaling proteins AKT,ERK,and Stat3.Therefore,Gab2 may be a disease-associated protein that is induced by pathogenic factors to amplify and coordinate multifactor-induced signals to govern disease development in the liver.Our research provides a novel potential target for the prevention and intervention of fatty liver disease.