Glial cell line-derived neurotrophic factor (GDNF) and its receptors in human ovaries from fetuses, girls, and women

Objective: To investigate the expression of glial cell line-derived neurotrophic factor (GDNF) and its receptors, GDNF alpha 1 (GFR-alpha 1) and tyrosine kinase receptor for rearranged during transfection (RET), in human ovaries at the protein and mRNA levels. Design: Samples were prepared for immunohistochemical staining for GDNF, GFR-alpha 1, and RET and in situ hybridization for the mRNA of GFR-alpha 1. The mRNA expression of two GDNF isoforms and two RET isoforms was investigated by reverse transcription polymerase chain reaction. Setting: Infertility unit at a university-affiliated tertiary medical center. Patient(s): Fifteen patients who underwent pregnancy terminations at 21-35 gestational weeks and 28 girls/women aged 5-39 years who underwent ovarian laparoscopies. Intervention(s): None. Main Outcome Measure(s): Laboratory analysis of human ovarian specimens. Result(s): The GDNF protein was detected in oocytes of all samples. Granulosa cells (GCs) stained for GDNF in a portion of fetal samples and in all samples from girls/women. The proteins for GFR-alpha 1 and RET were detected in both oocytes and GCs with weak staining for the long RET isoform. GFR-alpha 1 mRNA transcripts were detected in oocytes and GCs from all samples. The mRNA transcripts for the two GDNF isoforms and the two RET isoforms were detected in all fetal and adult specimens. Conclusion(s): The presence of the receptors of GDNF in the GCs of human primordial follicles suggests that GDNF may be involved in the regulation of primordial follicular activation. (Fertil Steril (R) 2010; 93: 2565-71. (C) 2010 by American Society for Reproductive Medicine.)