Polycystic ovary syndrome is an endocrine and metabolic disorder that is common in women of reproductive age, and the incidence is 8–13%. Polycystic ovary syndrome leads to low fertility at reproductive age in women and is often associated with insulin resistance and obesity, metabolic syndrome, type 2 diabetes, gestational diabetes, and increased susceptibility to cardiovascular disease[7–10]. High concentrations of androgen secretion in the ovary was the pathophysiological basis of PCOS, which led to hyperandrogenemia and its related to hyperandrogenic symptoms .[11, 12]. In our study, the incidence of PCOS in BHR was 45.7%. Female BHR not only have hypertension, that the reproductive phenotype of BHR with PCOS was similar to that of PCOS animal model. The symptoms similar to those of PCOS include polycystic ovarian changes, hyperandrogenemia and high LH / FSH, weight gain and increase of gonadal fatty cells and peritoneal fatty cells.
The menstrual cycle of PCOS patients was sparse or amenorrhea. There were more than 12 small follicles in one or both ovaries with a diameter of 2-9mm. The estrous cycle of rats was similar to that of women, was also regulated by Hypothalamus-Pituitary ovary-Gonad axis[15, 16]. The basic characteristic of PCOS models of rodent animal was that the estrous cycle was irregular, and multiple cystic follicles in the ovary. The estrous cycle of BHR was shown that the ovaries were anovulatory, and normal and PCOS BHR could be distinguished before HE staining of ovarian pathology by estrous cycle. We found that the estrous cycle of BHR with PCOS was irregular, and the diestrus stage was prolonged, or even other stages of oestrus cycle were absent, which persisted in the diestrus stage. The estrous cycle of BHR with PCOS was similar to that of androgen and letrozole induced PCOS animal model[15, 18].
This study was observed with Hematoxylin and Eosin staining, that Contrary to mature follicles, they were replaced by multiple, enlarged cystic follicles and atretic follicles in BHR with PCOS. The ovarian morphology of BHR with PCOS was consistent with the clinical feature of human PCOS patients, and the ovarian phenotype for animal models[15, 18, 19]. The theca cells of the enlarged cystic follicle in the ovaries of BHR with PCOS was thickened, and the granules decreased. This phenomenon was consistent with the results of animal models induced by androgen induced PCOS animal model in rats or mice. About 33% of the testosterone was produced by the theca cells of ovaries. The thickened theca cells was associated with hyperandrogenemia and high LH level, which led to PCOS. Granulosa cell reduction was associated with low level of FSH, and the follicular growth could be inhibited by low level of FSH and hyperandrogenemia, which lead to increased atresia follicles . The endometrium of BHR with PCOS was thickened, which was consistent with PCOS animal model.
The increase of serum testosterone, estrone, LH and LH / FSH in BHR with PCOS was also consistent with the characteristics of PCOS animal model[19, 23]. The animal models of PCOS established by letrozole showed an increase in serum testosterone, LH and LH/FSH [15, 24]. The changes of serum sex hormone in these animal models were consistent with the BHR with PCOS. The female offspring of sheep and rhesus monkeys showed the consistent clinical characteristics of PCOS, and the change of sex hormone level was similar to that of the BHR with PCOS, when the sheep and rhesus monkeys were exposed to excessive androgen during pregnancy[25, 26].
Hypertension was associated with hyperandrogenemia, and the patients with PCOS has a high prevalence risk of hypertension. The relationship between hypertension and PCOS was not clear. Hypertension was a symptom of PCOS patients, or hypertension was a risk factor of PCOS? The systolic blood pressure and the diastolic blood pressure of BHR was 137.97 ± 7.12 mmHg and 95.01 ± 6.43 mmHg, respectively. The systolic blood pressure and the diastolic blood pressure of SHR was 183.63 ± 7.02 mmHg and 127.06 ± 7.38 mmHg. We found that the reproductive phenotype of some BHR was similar to that of animal model of PCOS, but it did not happen in female SHR.
The BHR inherited the genetic gene of hypertension, and it was often used as an animal model of chronic stress induced hypertension[3, 5]. The BHR was the offspring of female SHR and male WKY, with hypertension genetically. The hypothalamus pituitary adrenal axis of BHR was sensitive to environmental pressure. Women with PCOS usually had high blood pressure in their mothers and normal blood pressure in their fathers, which was similar to the family spectrum of BHR. The female BHR might become a new naturally animal model of PCOS, its reproductive phenotype was similar to other animal models of PCOS, and its maternal hypertension family spectrum was similar to human being.
This study found that the performance of animal models resembling PCOS in some female BHR was spontaneous. However, other PCOS animal models were prepared by exposure to excessive androgen, which were not consistent with the onset of human PCOS. In this study, the incidence of PCOS in female BHR was 45.7%, which was lower. We hypothesized that BHR is sensitive to environmental stress, and whether environmental stress has a role in inducing higher PCOS in female BHR. And the metabolic changes of female BHR with PCOS are the direction of our future research.
In summary, this study described the reproductive related physical performance of female BHR, Some female BHR suffered from a PCOS like condition, that was necessary to consider the impact of PCOS on low fertility and experimental results in the female BHR.