Histologic and morphologic effects of valproic acid and oxcarbazepine on rat uterine and ovarian cells.
OBJECTIVE
To determine the histologic and morphologic effects of valproic acid (VPA) and oxcarbazepine (OXC) on rat uterine and ovarian cells.


METHODS
Fifty-six female prepubertal Wistar rats (21-24 days old and weighing between 47.5 and 58.1 g) were divided equally into four groups, which were given drinking water (controls), 300 mg/kg/day of VPA, 100 mg/kg/day of OXC or VPA + OXC via gavage, for 90 days. Ovaries and uteri of rats on proestrous and diestrous phases of estrous cycle were extirpated and placed in a fixation solution. The tissue specimens were assessed with apoptosis (TUNEL) staining protocols, eosinophil counting, and electron microscopic techniques.


RESULTS
In uteri, apoptosis in stroma, mitochondrial swelling, and cristolysis were observed in the VPA group, and OXC led to negative effects on epithelial cell and intracellular edema. In ovaries, both drugs increased apoptosis and intracytoplasmic edema. Organelle structure disruption was also observed in the OXC group. More conspicuous degenerative modifications were determined in the VPA + OXC group. In uteri, the number of TUNEL-positive luminal epithelial cells was 7.20 +/- 1.32 in controls, and significantly increased to 29.60 +/- 1.58, 34.20 +/- 2.53, and 54.80 +/- 2.04 in VPA, OXC, and VPA + OXC groups, respectively (p < 0.001). The highest number of TUNEL-positive glandular epithelium cells was observed in the VPA + OXC group; however, the number of TUNEL-positive stroma cells was highest in the VPA group. The highest number of eosinophils in stroma was in the VPA group.


CONCLUSIONS
VPA and OXC trigger apoptotic and degenerative effects on rat uterine and ovarian cells. VPA also prevents implantation of embryo to the uterus and causes abortion via endometrial eosinophil infiltration.
Cansu
Ali
A
Department of Pediatric Neurology, Karadeniz Technical University, 61080 Merkez/Trabzon, Turkey. acansu2003@yahoo.com
Erdogan
Deniz
D
Serdaroglu
Ayse
A
Take
Gülnur
G
Coskun
Zafer K
ZK
Gurgen
Seren G
SG
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002452:Cell Count; D003593:Cytoplasm / Q000187:drug effects / Q000648:ultrastructure; D010064:Embryo Implantation / Q000187:drug effects; D004717:Endometrium / Q000166:cytology / Q000187:drug effects; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D004847:Epithelial Cells / Q000187:drug effects / Q000648:ultrastructure; D004848:Epithelium / Q000187:drug effects; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D020287:In Situ Nick-End Labeling; D008854:Microscopy, Electron / Q000706:statistics & numerical data; D008933:Mitochondrial Swelling; D010053:Ovary / Q000166:cytology* / Q000187:drug effects*; D000078330:Oxcarbazepine; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D014599:Uterus / Q000166:cytology* / Q000187:drug effects*; D014635:Valproic Acid / Q000494:pharmacology*
D000927:Anticonvulsants; D002220:Carbamazepine; D014635:Valproic Acid; D000078330:Oxcarbazepine