Context: Wenshen Yangxue decoction (WSYXD) is a famous traditional Chinese medicine (TCM) formula and has been used in infertility treatment, but the exact mechanism is still unknown.Objectives: To determine if WSYXD improves endometrial receptivity recovery and promotes endometrial angiogenesis in a rat model.Materials and methods: A total of 100 proestrus female SPF Wistar rats were randomly assigned into five groups: control (saline), model (saline and hydroxyurea solution), high (5.2/100 g), middle (2.6/100 g) and low (1.3/100 g) WSYXD dose groups for 10 d. The microvessel densities, endometrial microstructure, as well as blastocysts number, were observed, followed by detection of angiogenesis-related gene/protein expression by immunohistochemistry, western blot and quantitative real-time polymerase chain reaction (RT-PCR), respectively.Results: Compared with the model group, the blastocyst number in WSYXD middle and high groups were significantly increased (4.50 ± 3.11 vs. 13.00 ± 2.12, 14.00 ± 1.83, p < 0.01). Lower MVD can be found in the model group (4.7) when compared with the normal control (13.7), middle (8.4) and high (9.7) dose groups. Additionally, significant differences were observed in VEGF, HIF-1α, p-AKT, p-PI3K, Ang1 and Ang2 (all p < 0.01) among different groups.Discussion and conclusions: In conclusion, WSYXD could help endometrial receptivity recovery and promote endometrial angiogenesis through PI3K, HIF-1α signalling and VEGF expression regulation. This study provides molecular evidence for application of WSYXD in the clinic and promotes new drug development from TCM.

Recurrent spontaneous abortion (RSA) occurs in 1–5% of parturients. The sustained therapy and research for RSA is expensive, which is a serious issue faced by both patients and doctors. The aim of the present study was to detect protein expression profiles in the serum of RSA patients and healthy controls, and to identify potential biomarkers for this disease. A 1,000-protein microarray consisting of a combination of Human L-507 and L-493 was used. The microarray data revealed that eight serum protein expression levels were significantly upregulated and 143 proteins were downregulated in RSA patients compared with the healthy controls. ELISA individually validated 5 of these 151 proteins in a larger cohort of patients and control samples, demonstrating a significant decrease in insulin-like growth factor-binding protein-related protein 1 (IFGBP-rp1)/IGFBP-7, Dickkopf-related protein 3 (Dkk3), receptor for advanced glycation end products (RAGE) and angiopoietin-2 levels in patients with RSA. Sensitivity and specificity analyses were calculated by a receiver operating characteristics curve, and were revealed to be 0.881, 0.823, 0.79 and 0.814, with diagnostic cut-off points of 95.44 ng/ml for IFGBP-rp1, 32.84 ng/ml for Dkk3, 147.27 ng/ml for RAGE and 441.40 ng/ml for angiopoietin-2. The present study indicated that these four proteins were downregulated in RSA samples and may be useful as biomarkers for the prediction and diagnosis of RSA. Subsequent studies in larger-scale cohorts are required to further validate the diagnostic value of these markers.

Objective: Traditional Chinese medicine (TCM) is an effective management to infertility. The association between TCM-mediated fertility and inhibition of phosphatidylinositol-3-kinase (PI3K) would be investigated.Methods: Institute of Cancer Research mice were treated with three herbal decoctions, named Wenshen Yangxue formula, Wenshen formula, and Yangxue formula, plus with human gonadotropins. PI3K inhibitor wortmannin was administrated to half of mice. Some index such as body weight, fertility ability would be investigated. The expression of P13K/Akt signaling was detected by using Western blot analysis. Results: No difference was observed in body weight among groups. Mice receiving the administration of human gonadotropins and herbal decoctions showed increased follicle numbers, percentage of fertilization, and promoted embryonic development. The treatment of Wenshen Yangxue formula decoction showed the highest efficiency, significant higher than Wenshen and Yangxue formulas. And increased the expression of p-PI3K and p-Akt proteins.Conclusion: These results suggested the herbal decoctions promoted the fertilization of mice, which was related to the charge of PI3K/Akt activation. K E Y W O R D Sinfertility, phosphatidylinositol-3-kinase, traditional chinese medicine, wortmannin