Limbic seizures alter reproductive function in the female rat

Purpose: Reproductive dysfunction and endocrine disorders are common among women with temporal lobe epilepsy. This study used the kindled rat model to test the hypothesis that limbic seizures directly contribute to reproducti ve dysfunction. Methods: Kindling electrodes were implanted in the basolateral amygdala in adult female rats. Females were kindled by either brief, daily, suprathresh old stimulations with a bipolar electrode or sham-kindled (controls). Elect rographic and behavioral seizures were monitored. Estrous cycles also were monitored with daily vaginal smears. Results: Seizures arrested ovarian cyclicity in all (n = 42) kindled animal s, the rats exhibiting persistent vaginal cornification (PVC). In these ani mals PVC was associated with high serum estradiol, increased pituitary weig ht, and polyfollicular ovaries consisting of many cystic follicles, as well as follicles in various stages of growth and atresia. In 93% of females, t his effect occurred after the development of stage 5 motor seizures, when f ocal seizures had secondarily generalized. In contrast, only five (21%) of 24 sham-kindled controls exhibited PVC. A single injection of progesterone (P-4) temporarily restored cyclicity in five (18%) of 28 kindled females ex hibiting PVC. In contrast, P-4 administration restored cyclicity in all fiv e sham-kindled controls that had spontaneously stopped cycling. P-4 treatme nt to kindled females in PVC resulted in a different endocrine profile than that in non-P-4-treated, kindled rats in PVC. P-4-treated rats had high se rum estradiol, testosterone, and prolactin levels; they showed an increase in pituitary weight; and their ovaries contained numerous corpora lutea and cystic follicles surrounded by markedly overdeveloped thecal cell layers. Conclusions: Seizures initiated in the amygdala result in impairment of the hypothalamic-pituitary axis, resulting in loss of ovarian cyclicity.