TRANSPLANTATION OF THE FETAL OLFACTORY PLACODE RESTORES REPRODUCTIVE-CYCLES IN FEMALE RHESUS-MONKEYS (MACACA-MULATTA) BEARING LESIONS IN THE MEDIAL BASAL HYPOTHALAMUS

The purpose of this study was to determine whether loss of the reprodu ctive cycle after lesions of the medial basal hypothalamus can be reve rsed by transplantation of the embryonic olfactory placode (OP) into f emale rhesus monkeys. Seven adult female rhesus monkeys with regular m enstrual cycles received bilateral radiofrequency lesions in the arcua te nucleus and the median eminence. After confirmation of anovulation in these monkeys, four monkeys were stereotaxically implanted with the OP obtained from monkey fetuses on embryonic days 35-36. The remainin g three monkeys were similarly implanted with embryonic cerebellum (CB ) as a control. Fetuses were delivered by cesarean section, and the OP and CB were immediately dissected out using a stereomicroscope. Fetal tissue was then cut into small pieces (<1 mm(3)), mixed with artifici al cerebrospinal fluid containing small pieces of Gelfoam, and stereot axically injected into the infundibular recess of the third ventricle. The recovery of ovulatory cycles in recipient monkeys was observed fo r at least 6 months; sex skin color changes and menstrual records were obtained daily, and serum samples for LH, estrogen, and progesterone were obtained twice a week. Three of four OP-transplanted monkeys resu med their ovulatory cycles within 2 months, whereas the fourth monkey, an elderly female, failed to recover her cycle. In contrast, none of the three OP-transplanted monkeys resumed ovulatory cycles. Histologic al examination indicated that 1) lesion scars were present in the medi an eminence-stalk region as well as the medial basal portion of the ar cuate nucleus of all seven brains; and 2) cartilage was present in the third ventricles of the OP-implanted brains. Moreover, immunocytochem ical staining revealed that in all OP monkeys, small, round, and immat ure LHRH-positive cells with fine short processes were found in the th ird ventricle and/or median eminence-stalk region, whereas no similar LHRH cells were found in OP-transplanted monkeys. It is concluded, the refore, that implantation of LHRH neurons derived from the fetal OP ca n result in resumption of the ovulatory cycle in female monkeys whose own LHRH pulse-generating mechanisms were impaired. Moreover, the resu lts suggest that LHRH neurons derived from embryonic OP possess the ph ysiological functions necessary for the stimulation of gonadotropin se cretion.