Neurotrophin 4 enhances in vitro follicular assembly in human fetal ovaries

ObjectiveTo investigate the in vitro effect of neurotrophin 4 (NT-4) on follicular assembly in human fetal ovaries.DesignHuman ovarian tissue from fetuses at 19-20 gestational weeks was placed in organ culture for two weeks with NT-4. Control groups were cultured with a neutralizing antibody against NT-4.SettingInfertility unit at an university-affiliated tertiary medical center.Patient(s)Four patients who underwent pregnancy terminations at 19-20 gestational weeks.Intervention(s)None.Main Outcome Measure(s)Histologic findings of follicular assembly.Result(s)Follicular assembly was significantly increased in the specimens cultured with NT-4 than in the uncultured specimens, the samples cultured without NT-4, and samples cultured with the neutralizing antibody. In the second week of culture, additional follicular assembly was promoted in the presence of 100 ng/mL NT-4 but not with 10 ng/mL NT-4.Conclusion(s)This is the first report showing that NT-4 seems to promote human follicular assembly in fetal ovaries, probably in a dose-dependent manner. Follicular assembly is regulated by multiple signals, and additional studies on the effects of other growth factors in combination with NT-4 are warranted.