Seizures and reproductive function: Insights from female rats with epilepsy

Abstract

OBJECTIVE-Chronic seizures in women can have adverse effects on reproductive function, such as polycystic ovarian syndrome (PCOS), but it has been difficult to dissociate the effects of epilepsy per se from the role of antiepileptic drugs (AEDs). To distinguish the effects of chronic seizures from AEDs, we used the laboratory rat, where an epileptic condition can be induced without concomitant AED treatment.METHODS-Adult female rats were administered the chemoconvulsant pilocarpine to initiate status epilepticus (SE), which was decreased in severity by the anticonvulsant diazepam. These rats developed spontaneous seizures in the ensuing weeks, and are therefore termed "epileptic." Controls were saline-treated rats, or animals that were injected with pilocarpine but did not develop SE. Ovarian cyclicity and weight gain were evaluated for 2-3 months. Serum hormone levels were assayed from trunk blood, collected at the time of death. Paraformaldehyde-fixed ovaries were evaluated quantitatively. RESULTS-Rats that had pilocarpine-induced seizures had an increased incidence of acyclicity by the end of the study, even if SE did not occur. Ovarian cysts and weight gain were significantly greater in epileptic rats than controls, whether rats maintained cyclicity or not. Serum testosterone was elevated in epileptic rats, but estradiol, progesterone and prolactin were not. INTERPRETATIONS-The results suggest that an epileptic condition in the rat leads to increased body weight, cystic ovaries and elevated testosterone levels. Although caution is required when comparing female rats to women, the data suggest that epilepsy per se may be sufficient to induce abnormalities in the control of the ovary.

Impact of rapamycin on status epilepticus induced hippocampal pathology and weight gain

“…Pilocarpine epileptogenesis leads to obesity in rodents (Scharfman et al, 2008; Ruiz et al, 2011) and a similar phenomenon has been described in patients with epilepsy (Daniels et al, 2009). In the present study, SE+Veh mice exhibited a significant 35% increase in body weight over the course of the experiment (p<0.001, one-way RM ANOVA).…”

“…Pilocarpine status epilepticus leads to obesity in rodents (Scharfman et al, 2008; Ruiz et al, 2011). Obesity is also a common comorbidity of human epilepsy (Ladino et al, 2014; Janousek et al, 2013).…”

Sex differences in the neurobiology of epilepsy: A preclinical perspective

“…In kindling, for example, females often develop persistent estrus (Edwards et al, 1999) where a high level of estrogen develops chronically. Irregular estrous cycles typically occur in models of TLE that use SE as the initial insult (Amado and Cavalheiro, 1998; Scharfman et al, 2008). Polycystic ovaries and increased androgen levels can develop, adding additional experimental factors (Scharfman et al, 2008).…”

“…Irregular estrous cycles typically occur in models of TLE that use SE as the initial insult (Amado and Cavalheiro, 1998; Scharfman et al, 2008). Polycystic ovaries and increased androgen levels can develop, adding additional experimental factors (Scharfman et al, 2008). Although interesting because women with epilepsy can develop polycystic ovaries and increased androgen levels, it is difficult to use laboratory animals to explore sex differences in epileptogenesis because inducing convulsive seizures causes a loss or dramatic alteration in normal gonadal hormones.…”

Epilepsi Tedavisi Alan Kadın Hastalarda Hipotalamo-Pituiter-Gonadal Aksın Değerlendirilmesi

“…Reproductive anomalies and high levels of luteinizing hormone (LH) and altered LH: follicule-stimulating hormone (FSH) ratio have been reported in epileptic women (6). Besides, Scharfman et al demonstrated that an epileptic condition in the rat leads to increased body weight, cystic ovaries and elevated testosterone levels (7).…”