Ontogeny of gonadotropin-releasing hormone-containing neurons in early fetal development of rhesus macaques

Abstract

We studied the ontogeny of GnRH neurons in fetal rhesus macaques from days 36-135 of gestation. The nasal region, pituitary, and brain were dissected, fixed in 4% paraformaldehyde, sectioned on a cryostat at 10 microns, and mounted on slides. Immunocytochemistry and in situ hybridization were performed for GnRH, pro-GnRH, and pro-GnRH mRNA on nasal and brain tissues. Immunoreactive LH, FSH, and PRL were determined in developing pituitary glands. At 36 days, clusters of GnRH cells were found in the nasal region only. GnRH fibers extended into the brain, and large bundles projected laterally toward the basal hypothalamus. By day 38 GnRH cells were also localized in the olfactory region of the brain. With increasing fetal age a gradual caudal extension of GnRH cells occurred. These cells were first observed in the basal hypothalamus at 47 days. Cells containing PRL and gonadotropins (LH and FSH) were detected in the pituitary at 47 and 50 days, respectively. Low levels of pro-GnRH mRNA were present in the nasal epithelium and septum by day 38 of gestation. The levels of pro-GnRH mRNA in the nasal area and the brain remained low in the day 50 fetus, but were increased significantly by day 135. These data suggest that GnRH neurons in the primate brain originate in the nasal region. Furthermore, GnRH neurons exhibit low levels of synthetic activity at the early fetal stages, but higher synthetic activity close to term.