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 reproductive dysfunction. Methods: Kindling electrodes were implanted in the basolateral amygdala in adult female rats. Females were kindled by either brief, daily, suprathreshold stimulations with a bipolar electrode or sham-kindled (controls). Electrographic and behavioral seizures were monitored. Estrous cycles also were monitored with daily vaginal smears. Results: Seizures arrested ovarian cyclicity in all (n = 42) kindled animals, the rats exhibiting persistent vaginal cornification (PVC). In these animals PVC was associated with high serum estradiol, increased pituitary weight, and polyfollicular ovaries consisting of many cystic follicles, as well as follicles in various stages of growth and atresia. In 93% of females, this effect occurred after the development of stage 5 motor seizures, when focal 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 exhibiting PVC. In contrast, P-4 administration restored cyclicity in all five sham-kindled controls that had spontaneously stopped cycling. P-4 treatment 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 serum 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.