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Objective To investigate the optimal preparation method of bisphenol A (BPA) -induced diminished ovarian reserve (DOR) rat models, and to clarify the attributes of traditional Chinese medicine (TCM) syndromes. Methods Eighteen clean female SD rats aged 3 and 6 months with regular estrous cycle were selected and were randomly divided into the low-dose, medium-dose and high-dose BPA groups. The rats in the low-dose, medium-dose and high-dose BPA groups were given 50，100，and 200 mg/kg BPA mixed suspension orally, once a day until they showed unregular estrous cycles. The general performance and vaginal smear were observed everyday. The estrous cycle of rats was observed by vaginal smear; the abdominal aortic blood of rats was collected, and serum was separated. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), anti-Müllerian hormone (AMH), and inhibin-B (INHB) were detected by ELISA. We took bilateral ovaries, observed the morphology of ovarian tissues, and calculated the proportion of follicles at all levels and the ovarian index. We chose the model preparation method used in the group which had the most significant change of the indexes as the best method. The 18 successful model rats were randomly divided into the control group, Yougui pill group, and Yangjingzhongyu decoction group, with 6 in each. The model rats in the control group， Yougui pill group and Yangjingzhongyu decoction group were given distilled water, Yougui pill for treatment of kidny-yang deficiency, and Yangjingzhongyu decoction for kidny-yin deficiency by 1 mL/100 g body weight, for 2 consecutive weeks， respectively. The changes of estrous cycle, symptoms of kidney-yang deficiency, ovarian tissue morphology, ovarian index, proportion of follicles at all levels, serum hormone, INHB and AMH levels were compared between these two groups. Results All model rats in the BPA groups aged 3 and 6 months had reduced activity and liked to crouch and bunch. The disturbance time of estrous cycles of model rats aged 3 month in the medium-dose BPA group was significant shorter as compared with that of the other groups, and they showed decreased levels of AMH and primordial follicles and increased atretic follicles. Therefore, the preparation method in the 3-month-old rat model of the medium-dose BPA group was the best method. One rat in the Yangjingzhongyu decoction group and 5 rats in Yougui pill group resumed regular estrous cycle while all rats in the control group continued to be in disorder. The number of regular estrus cycle recovery in the Yougui pill group （5）was higher than that in the control group（0）and Yangjingzhongyu decoction group (1), while the symptom of kidneyyang deficiency improved more significantly. The ovaries of rats in the control group were pale, small and hard, while those of the Yougui pill group were bigger and ruddy. The ovaries of Yougui pill group had good elasticity and multiple growth follicles on the surface. There were fewer follicles on the ovarian surface and poor elasticity in the rats of Yangjingzhongyu decoction group. Compared with the other two groups, the Yougui pill group had higher proportion of primordium follicle, lower atresia follicle, and higher AMH level (all P<0. 05). Conclusions The DOR animal models can be successfully prepared by intragastric administration of 100 mg/kg BPA in 3-month clean SD rats. The attribute of TCM syndrome of the rat models is kidney-yang deficiency by means of syndrome differentiation through formula. [ABSTRACT FROM AUTHOR]

Objective: To study the influence of perinatal exposure of bisphenol A (BPA) at a low dose on the spermatogenesis of male offspring rats. Methods: Pregnant rats were injected subcutaneously with BPA 2 μg/(kg·d) from gestation day 10 through lactation day 7, and the same volume of olive oil was used as the blank control. Their male offspring were served as the BPA group and the control group. Histological structure of the testis and the related regulation genes such as cyclin A1、cyclin B、c-jun and c-fos, as well as the FSH and LH, were tested, and the expressions POA-GnRH or ARC-kiss1 mRNAs were also examined in their male offspring during the postnatal day 18, 21, 24. Results: In comparison with the control group, the seminiferous tubular diameter, the number of round spermatids and the ratio of seminiferous tubule with round spermatids were significantly increased in PND24 BPA rats (P＜0.05). The expression levels of cyclin A1, c-jun and c-fos mRNAs in the testes were significantly elevated in PND21 BPA rats (P＜0.01). Similarly, the levels of plasma FSH and LH were increased in the PND21/24 BPA rats compared with the control rats (P＜0.05). But the levels of plasma T and E2 were no significant in the PND18/21/24 BPA rats and the control rats (P＞0.05). In comparison with control group, the expression levels of POA-GnRH mRNA and ARC-kiss1 mRNA were significantly increased in PND21 BPA rats (GnRH: P＜0.05; kiss1: P＜0.01). Conclusions: In addition to the direct effect of BPA on the testes of male offspring, the perinatal exposure to a low dose of BPA promotes spermatogenesis via advancing the pubertal activation of ARC -kisspeptin, and via further enhancing the expressions of meiotic regulation genes in the testes of male offspring. [ABSTRACT FROM AUTHOR]