Neurotrophin 4 enhances in vitro follicular assembly in human fetal ovaries

Objective To investigate the in vitro effect of neurotrophin 4 (NT-4) on follicular assembly in human fetal ovaries. Design Human 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. Setting Infertility 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.