Follicular dynamic and immunoreactions of the vitrified ovarian graft after host treatment with variable regimens of melatonin.
OBJECTIVE
This study investigates dose-dependent effects of melatonin on ovarian graft.


METHODS
Vitrified-thawed whole ovaries of newborn mice were grafted into ovariectomized mature ones. Melatonin (20, 50, 100, and 200 mg/kg/day) was administrated to separate groups of host mice for 32 days. IgM and IgG antibodies, Th1 and Th2 cytokines, and melatonin in recipient's blood were measured. Subsequent survival of the grafted ovaries was scored. An assessment of follicular morphology was performed using TUNEL assay and hematoxylin-eosin staining.


RESULTS
The administration of melatonin did not disturb the circadian rhythm of melatonin concentration. The ovarian graft lifespan was prolonged at 200 mg/kg/day melatonin (P < 0.001). However, in doses of higher than 20 mg/kg/day melatonin, the proportion of healthy follicles and ovary size decreased. Th1 cytokines levels were reduced dose dependently. However, the effect of melatonin on Th2 cytokines was not pronounced. IgM and IgG2a decreased in recipients receiving 200 mg/kg/day melatonin in comparison with non-treated group (P < 0.001), while this variables were significantly increased at the dose of 50 mg/kg/day (P < 0.001).


CONCLUSIONS
Melatonin at 200 mg/kg/day has an immunosuppresent effect and produce prolongation of graft survival. However, the associated reduction in healthy follicles suggests that melatonin in doses of higher than 20 mg/kg/day has no preventative ischemic action.
Cellular and Molecular Research Center, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Iran. mhemadi@razi.tums.ac.ir
Masoud
M
Hemadi
Saeed
S
Shokri
Elham
E
Pourmatroud
Farideh
F
Moramezi
Ali
A
Khodadai
D000818:Animals; D016207:Cytokines / Q000097:blood; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D008550:Melatonin / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010053:Ovary / Q000276:immunology* / Q000473:pathology / Q000637:transplantation*; D019737:Transplants
D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D008550:Melatonin