Expression and cellular distribution of insulin-like growth factor 1 receptor during window of implantation in infertile women with intramural fibroids

Annu Makker, Madhu Mati Goel, Dipti Nigam, Amita Pandey


Background: The “window of implantation” (WOI) is a transient but well defined period during which the hostile endometrial lining is transformed to a surface receptive to accept the embryo. Recently, data are beginning to accumulate suggesting negative influence of non-cavity distorting intramural uterine fibroids (NCD-IMF) on endometrial receptivity that may have implications for implantation failure. However, molecular mechanisms underlying infertility associated with NCD-IMF remain unclear. The aim of present study was to examine the expression and cellular distribution of insulin-like growth factor 1 receptor (IGF1R) during WOI in infertile women with NCD-IMF and fertile controls. While, reports are available that support role of IGF1R in mediating adhesive interaction with the implanting blastocyst, the effect of NCD-IMF on IGF1R expression during the WOI is not defined.

Methods: Quantitative real-time polymerase chain reaction and immunohistochemistry were used to evaluate messenger RNA (mRNA) and protein expression of IGF1R in midsecretory endometrial biopsies obtained from infertile women with NCD-IMF (n=20) and healthy fertile controls (n=10).

Results: As compared to fertile controls, significantly higher IGF1R: i) mRNA levels (1.59 fold up regulation; p=0.044) and ii) immunoscore in the luminal epithelium (8.94±3.13 versus 6.31±1.49; p=0.009) were observed in infertile women with NCD-IMF.

Conclusions: Over expression of IGF1R in infertile women with NCD-IMF, during the window of receptivity, may result in altered ability of uterine epithelial cells for blastocyst adhesion and subsequent implantation, which might lead to poor reproductive outcome in these women.


IGF1R, Immunohistochemistry, Intramural fibroids, RT-PCR, Window of implantation

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Bulun SE. Uterine fibroids. N Engl J Med. 2013;369(14):1344-55.

Baird DD, Dunson DB, Hill MC, Cousins D, Schectman JM. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol. 2003;188:100-7.

Olive DL, Pritts EA. Fibroids and reproduction. Semin Reprod Med. 2010;28:218-27.

Pritts EA, Parker WH, Olive DL. Fibroids and infertility: an updated systematic review of the evidence. Fertil Steril. 2009;91:1215-23.

Christopoulos G, Vlismas A, Salim R, Islam R, Trew G, Lavery S. Fibroids that do not distort the uterine cavity and IVF success rates: an observational study using extensive matching criteria. BJOG. 2017;124:615-21.

Pier BD, Bates GW. Potential causes of subfertility in patients with intramural fibroids. Fertil Res Pract. 2015;1:12-20.

Unlu C, Celik O, Celik N, Otlu B. Expression of endometrial receptivity genes increase after myomectomy of intramural leiomyomas not distorting the endometrial cavity. Reprod Sci. 2016;23:31-41.

Makker A, Goel MM, Nigam D, Bhatia V, Mahdi AA, Das V, et al. Endometrial expression of homeobox genes and cell adhesion molecules in infertile women with intramural fibroids during window of implantation. Reprod Sci. 2017;24:435-44.

Makker A, Goel MM, Nigam D, Mahdi AA, Das V, Agarwal A, et al. A berrant Akt activation during implantation window in infertile women with intramural uterine fibroids. Reprod Sci. 2018;25:1243-53.

Makker A, Singh MM. Endometrial receptivity in relation to fertility, infertility and antifertility: clinical assessment using structural, biochermical and molecular markers. Med Res Rev. 2006;26:699-746.

Green CJ, Frase ST, Day ML. Insulin-like growth factor 1 increases apical fibronectin in blastocysts to increase blastocyst attachment to endometrial epithelial cells in vitro. Hum Reprod. 2015;30:284-98.

Ghahary A, Murphy LJ. Uterine insulin-like growth factor-I receptors: regulation by estrogen and variation throughout the estrous cycle. Endocrinol. 1989;125:597-604.

Wu RJ, Zhou FZ. Insulin-like growth factor II and its receptor gene expression in the endometrium of women with unexplained infertility. Zhonghua Fu Chan Ke Za Zhi. 2004;39:242-5.

Ghazal S, McKinnon, Zhou J, Mueller M, Men Y, Yang L, et al. H19 lncRNA alters stromal cell growth via IGF signaling in the endometrium of women with endometriosis. EMBO Mol Med. 2015;7:996-1003.

Noyes RW, Hertig AT, Rock J. Dating the endometrial biopsy. Fertil Steril. 1950;1:3-25.

Baker J, Hardy MP, Zhou J, Bondy C, Lupu F, Bellve AR, et al. Effects of an IGF1 gene null mutation on mouse reproduction. Mol Endocrinol. 1996;10:903-18.

Kang YJ, Lees M, Mathhews LC, Kimber SJ, Forbes K. miR-145 suppresses embryo-juxtracrine communication at implantation by modulating maternal IGF1R. J Cell Sci. 2015;128:804-14.