Evidence from three cohort studies on the expression of MUC16 around the time of implantation suggests it is an inhibito

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REPRODUCTIVE PHYSIOLOGY AND DISEASE

Evidence from three cohort studies on the expression of MUC16 around the time of implantation suggests it is an inhibitor of implantation Liu Liu 1 & Yangyang Wang 1 & Xiaoyan Chen 2 & Yichao Tian 1 & Tin Chiu Li 2 & Lijuan Zhao 1 & Qiaoqiao Chen 1 & Mingling Wei 1 & Songying Zhang 1 Received: 9 January 2020 / Accepted: 27 March 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract Purpose To examine the expression of MUC16 in the endometrium peri-implantation period in three different cohort studies. Methods This was a retrospective observational cohort study. A total of 245 participants were recruited in three separate cohort studies: (1) women with recurrent miscarriage (n = 50) and fertile controls (n = 29); (2) women who had high (n = 20) or normal (n = 20) progesterone on the day of hCG trigger in ovarian stimulation cycle for IVF; and (3) women who did (n = 95) or did not (n = 31) conceive following frozen embryo transfer in HRT cycles. All subjects had archived endometrial samples precisely taken on LH+7 in natural cycles, or hCG+6 in ovarian stimulation cycles, or P+5 in HRT cycles. The H-score (median, range) of MUC16 in the luminal epithelium and glandular epithelium was determined by using immunohistochemistry. Results The median (range) of H-score of MUC16 in the luminal epithelium (1) in women with recurrent pregnancy loss was 23.7 (0–300), which was significantly (P < 0.05) lower than that of 118.4 (7.7–300) in fertile controls; (2) in women with elevated progesterone on the day of hCG administration (147.8, 18.0–230.1), significantly (P < 0.05) higher than that of women with normal progesterone (61.0, 2.3–205.3); (3) in women who conceived (23.1, 0–250.3), significantly (P < 0.001) lower than that in women who did not conceive (58.4, 0–300). Conclusion The expression of MUC16 in all three cohort studies is consistent with it being an inhibitor of implantation. Keywords Mucin 16 . Adhesion molecules . Luminal epithelial . Implantation . Inhibitor

Introduction The process of implantation is tightly controlled by a number of promoters and inhibitors. Many previous studies focused on promoters such as integrins [1], LIF [2], pinopodes [3], or HOXA10 [4]. Relatively little attention has been given to the role played by inhibitors. Earlier studies suggested that the Liu Liu and Yangyang Wang contributed equally to this work. * Songying Zhang [email protected] 1

Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3# Qingchun East Road, Hangzhou 310016, People’s Republic of China

2

Assisted Conception Unit, Department of Obstetrics & Gynecology, Chinese University of Hong Kong, Hong Kong SAR, China

MUC family acts as inhibitors in the implantation process [5–7]. Among the MUC family, MUC1 had been more frequently studied but the results were controversial with some literatu