Efeito do gel intravaginal com 4-vinilciclohexeno diepóxido sobre os ovários de ratas

Abstract

The overpopulation of stray dogs and cats damages public health, biodiversity, and the animals themselves that survive without conditions of well-being. For reproductive control, the most commonly used method is sterilization, with surgical options (orchiectomy and ovariohysterectomy) being the most applied. However, the method is inefficient for mass population control of stray animals. Thus, alternative and less invasive methods have been studied. Therefore, chemical sterilization shows it self as a promising alternative, but with the limitation of having practically exclusive use in males. It is known that for effective population control, the methods must be useful in both sexes. In this context, the chemical compound 4-vinylcyclohexene diepoxide (4-VCD), has been used in rodents to induce loss of ovarian follicles and mimic human menopause. The compound shows selective ovotoxicity, accelerating the atresia process in primordial and primary follicles, culminating in premature ovarian failure. For this, the compound is used by the intraperitoneal route, considered invasive and prone to complications. In order to use the 4-VCD for the population control of wandering females (bitches and cats) it is necessary to study a less invasive and effective route. Thus, the objective of the present study was to evaluate the effect of 4-VCD on the ovaries and their chemosterilizing potential, through inoculation of intravaginal gel in experimental models. For this purpose, 20 adult Wistar rats were used, equally and randomly divided into two groups, according to the treatment received: control and treated with gel containing 4-VCD. The control group received 0.2 mL of chitosan-based gel and the treatment group received the same gel, containing 4-VCD at a dose of 160 mg/kg. The inoculations were daily for 15 consecutive days. The rats were evaluated daily by vaginal cytology until euthanasia. The animals were euthanized at two different times (half of the group each): 16 days after the start of treatment (M1) or after 30 days (M2). The ovaries were collected, prepared, and assessed under light microscopy to count primordial and primary follicles and their classification into healthy or atretic. Irregularities in the estrous cycle of rats were noted in the treated group, with prolongation in the diestrus phases in M1 and M2; in M2, prolongation of the estrus phase was also observed. In the group treated with 4-VCD, there was a decrease in the number of estrous cycles compared to the control. The follicular evaluation revealed an increase in the proportion of primordial atresia follicles in the treated group compared to the control group at both times of evaluation. In contrast, in the control group, there was a higher proportion of healthy primordial follicles, when compared to the treatment group, at both times. In the global follicle count in M2, the treated group had a higher mean of primordial atretic follicles compared to the control group. Thus, it was possible to observe the ovotoxic action of 4-VCD through the intravaginal route in chitosan gel. However, treatment for 15 days with intravaginal gel composed of 4-VCD at a dose of 160 mg/kg did not promote ovarian failure during the experiment period. Future studies should be carried out in order to determine the exposure time and ideal dose, sufficient to promote infertility in rats.