Functional recovery of the developing rat ovary after transplantation: contribution of the extrinsic innervation.
These experiments were undertaken to define the neuroendocrine mechanisms underlying the recovery of ovarian function after transplantation to an ectopic site. Both ovaries from 23-day-old rats were transplanted to the region of the neck, next to the jugular vein. Serum gonadotropin and plasma immunoreactive inhibin-alpha levels were determined at several intervals thereafter. Serum estradiol (E2) was measured during the first week posttransplantation. Reinnervation of the ovary by sympathetic and sensory nerves was monitored by immunohistochemistry. Sympathetic nerves were identified as adrenergic by the presence of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, and as peptidergic, by their neuropeptide-Y (NPY) or vasoactive intestinal peptide (VIP) immunoreactivity. Sensory nerves were identified by the presence of substance P (SP) and calcitonin-gene related peptide (CGRP) immunoreactivity. Serum LH and FSH increased, and plasma inhibin levels decreased, within 48 h after transplantation. Serum LH reached maximum levels on day 4, decreasing rapidly thereafter to basal values by day 6. These changes were functionally correlated with the posttransplantation fluctuations in serum E2, which decreased at 48 h, rebounded by day 4, and returned to basal values on day 7. Removal of the transplanted ovaries on day 3 resulted in the disappearance of serum E2 levels on day 4, thus confirming the ovarian graft as the source of E2. In contrast to LH, serum FSH remained significantly elevated for at least 3 weeks after transplantation, then decreased to basal levels after day 21, coinciding with the rise in inhibin secretion. Although a substantial loss of follicles was noted 48 h after transplantation, quantitative examination of the changes on day 4 revealed that approximately 40% of antral follicles were not necrotic. Ovulation and formation of corpora lutea were noted 21 days after transplantation. Reinnervation of the transplanted ovary by TH-, VIP-, NPY-, SP-, and CGRP-containing fibers was first detected 7 days after transplantation. Although VIP reinnervation was sparse and only transiently detected (days 7-21), the density of sympathetic (TH, NPY) and sensory (SP, CGRP) fibers increased 2- to 3-fold between days 7-28, remaining unchanged thereafter. Since apparent completion of this reinnervation coincided with reestablishment of normal levels of both LH and FSH, an additional experiment was performed to determine if the two events were causally related.(ABSTRACT TRUNCATED AT 400 WORDS)
Division of Neuroscience, Oregon Regional Primate Research Center, Beaverton 97006.
H E
HE
Lara
W L
WL
Dees
J K
JK
Hiney
G A
GA
Dissen
C
C
Rivier
S R
SR
Ojeda
D000818:Animals; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007158:Immunologic Techniques; D007265:Inhibins / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D009416:Nerve Regeneration; D009424:Nervous System Physiological Phenomena; D010053:Ovary / Q000294:innervation / Q000502:physiology / Q000637:transplantation*; D011184:Postoperative Period; D051381:Rats; D013562:Sympathectomy; D016042:Transplantation, Heterotopic
D007265:Inhibins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone