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Endometrial Receptivity Markers in Mice Stimulated With Raloxifene Versus Clomiphene Citrate and Natural Cycles

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Abstract

Ovulation induction therapy with clomiphene citrate can suppress endometrial receptivity. Raloxifene may be an alternative therapeutic for women with ovulatory disorders. This study aimed to compare the expression of endometrial receptivity markers, including homeobox gene 10 (HOXA10), integrin β3, and leukemia inhibitory factor (LIF), as well as pinopode production during the implantation window in mice stimulated with raloxifene and clomiphene citrate and natural cycles. Thirty-six 8-week-old female Kunming mice were randomly divided into 3 groups (n = 12) and administered daily raloxifene (22 mg/kg), clomiphene citrate (18 mg/kg), and normal saline (1 mL), respectively, by gavage. Two days later, mice were injected with 5 IU human chorionic gonadotropin and mated. Successfully mated female animals were identified with vaginal plugs designated gestation day 1. At day 4.5, pregnant donor mice were euthanized, and uterus samples were collected for immunohistochemistry, quantitative polymerase chain reaction, Western blot, and scanning electron microscopy analyses. Homeobox gene 10, integrin β3, and LIF messenger RNA (mRNA) and protein levels were significantly higher in the raloxifene-treated animals compared with the clomiphene citrate group (all P < .05) but not significantly different from saline group values, except for LIF and integrin β3 mRNA levels (P < .05). Pinopodes were abundant and well developed in the raloxifene and saline groups; however, in the clomiphene citrate-treated mice, fewer and poorly developed pinopodes were obtained. In mice, raloxifene had no effect on HOXA10, integrin β3, and LIF expression as well as pinopode production, suggesting it has no adverse effects on endometrial receptivity. Raloxifene may provide a viable alternative oral ovulation induction agent to clomiphene citrate.

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Authors and Affiliations

  1. Reproductive Medicine Center, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, China

    Cairong Chen MS & Song Quan MS

  2. Reproductive Medicine Center, People’s Hospital of Qingyuan, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan, China

    Cairong Chen MS, Qiuxia Yan MS, Xiuqin Zhou BS, Yingjie Xian BS & Xiaoying Zhao BS

  3. Department of Pathology, People’s Hospital of Qingyuan, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan, China

    Kunping Liu MD

  4. Department of Laboratory, People’s Hospital of Qingyuan, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan, China

    Dali Liang BS

  5. Department of Gynaecology and Obstetrics, People’s Hospital of Qingyuan, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan, China

    Xiaoyan Guo MS

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  1. Cairong Chen MS
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  2. Qiuxia Yan MS
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  9. Song Quan MS
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Correspondence to Song Quan MS.

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Chen, C., Yan, Q., Liu, K. et al. Endometrial Receptivity Markers in Mice Stimulated With Raloxifene Versus Clomiphene Citrate and Natural Cycles. Reprod. Sci. 23, 748–755 (2016). https://doi.org/10.1177/1933719115616496

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