Evidence-Based Complementary and Alternative Medicine
Volume 2015 (2015), Article ID 317586, 10 pages
http://dx.doi.org/10.1155/2015/317586
Research Article
Traditional Chinese Medicine, the Zishen Yutai Pill, Ameliorates Precocious Endometrial Maturation Induced by Controlled Ovarian Hyperstimulation and Improves Uterine Receptivity via Upregulation of HOXA10
Qi Gao,1 Lu Han,1 Xiumei Li,2 and Xia Cai3
1Department of Gynecology, Traditional Chinese Medical Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang 830000, China
2Department of Morphology Center, Xinjiang Medical University, Urumqi, Xinjiang 830000, China
3Reproductive Center, The First Teaching Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830000, China
Received 12 September 2014; Accepted 20 January 2015
Academic Editor: Xiu-Min Li
Copyright © 2015 Qi Gao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Controlled ovarian hyperstimulation (COH) is widely used in assisted reproductive technology (ART), but it often leads to precocious maturation of the endometrium such that it impairs embryonic implantation and limits pregnancy rates. Previous studies have shown the traditional Chinese medicine, the Zishen Yutai pill (ZYP), to be effective in treatment of threatened as well as recurrent miscarriages, and it can improve embryonic implantation rates in patients undergoing IVF treatment. In the present study, the ZYP has been found to ameliorate precocious endometrial maturation in a mouse model of different COH. Molecular evaluations, real-time PCR, relative RT-PCR, Western blotting, and immunohistochemistry have indicated that the ZYP increased the expression of HOXA10, an important marker of uterine receptivity. Elevation of HOXA10 led to further upregulation of its target gene, integrin β3, and downregulation of EMX2, two additional markers of uterine receptivity. In this way, the ZYP may mitigate COH-induced precocious maturation of the endometrium and improve uterine receptivity by upregulating HOXA10.
1. Introduction
It is estimated that over 4% of all infants born every year in the more developed countries are conceived using assisted reproductive technology (ART) [1]. However, despite years of attempts to improve the efficiency of ART, pregnancy rates still remain moderate and have not increased significantly [1, 2]. It has been suggested that this relatively low pregnancy rate is in large part due to the widespread use of a technique termed “controlled ovarian hyperstimulation” (COH) [3–5]. COH has been developed for the collection of a large number of follicles in order to retrieve mature oocytes. COH is achieved by daily injection of follicle-stimulating hormone (FSH) [6]. To prevent a surge in premature luteinizing hormone (LH) and premature ovulation, gonadotropin-releasing hormone (GnRH) agonist or antagonist is also injected [6]. However, ovarian stimulation often disturbs luteal cycles and induces abnormalities in endometrial development. These abnormalities manifest mainly as precocious maturation of the endometrium, which often leads to frequent glandular and stromal dyssynchrony in the mid-luteal phase [3–5]. Studies have suggested that this advanced maturation of the endometrium may account in large part for the failure of embryonic implantation [3–5]. Embryonic implantation is an essential step in the development of a pregnancy and its failure continues to impede treatment outcomes of ARTs [3]. A key factor determining the success of embryo implantation is the receptivity of the endometrium, which is often impaired by precocious endometrial maturation in ART cycles [3]. This has led to widespread adoption of clinical interventions aimed at improving endometrial receptivity in ART cycles [3].
The Zishen Yutai pill (ZYP) is a TCM formula that contains Cuscuta sinensis Lam., Fructus Amomi, Radix Rehmanniae Preparata, ginseng, Herba Taxilli, Colla Coriiasini, Polygonum Multiflorum, Artemisiae Argyi Folium, Morinda officinalis, Atractylodes macrocephala, Codonopsis Radix, cornu cervi degelatinatum, Fructus Lycii, Dipsaci Radix, and Eucommia ulmoides. It was first introduced by Professor Yuankai Luo [7].
The effectiveness of the ZYP in treatment of threatened or recurrent miscarriages has been supported by clinical studies [7, 8]. It has also been shown to improve embryonic implantation rates in patients undergoing embryo transfer [9]. Collectively, these results strongly suggest that the ZYP can improve receptivity of the endometrium in both natural luteal cycles and ART cycles. These results suggest that the ZYP acts through HOXA10 to ameliorate COH-induced endometrial defects and that it improves uterine receptivity.
