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Oviductal glycoprotein 1 (OVGP1) is expressed by endometrial epithelium that regulates receptivity and trophoblast adhesion

  • Reproductive Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

To study the regulation and functions of oviductal glycoprotein 1 (OVGP1) in endometrial epithelial cells.

Methods

Expression of OVGP1 in mouse endometrium during pregnancy and in the endometrial epithelial cell line (Ishikawa) was studied by immunofluorescence, Western blotting, and RT-PCR. Regulation of OVGP1 in response to ovarian steroids and human chorionic gonadotropin (hCG) was studied by real-time RT-PCR. OVGP1 expression was knockdown in Ishikawa cells by shRNA, and expression of receptivity associated genes was studied by real-time RT-PCR. Adhesion of trophoblast cell line (JAr) was studied by in vitro adhesion assays.

Results

OVGP1 was localized exclusively in the luminal epithelial cells of mouse endometrium at the time of embryo implantation. Along with estrogen and progesterone, hCG induced the expression of OVGP1 in Ishikawa cells. Knockdown of OVGP1 in Ishikawa cells reduced mRNA expression of ITGAV, ITGB3, ITGA5, HOXA10, LIF, and IL15; it increased the expression of HOXA11, MMP9, TIMP1, and TIMP3. Supernatants derived from OVGP1 knockdown Ishikawa cells reduced the adhesiveness of JAr cells in vitro. Expression of OVGP1 mRNA was found to be significantly lowered in the endometrium of women with recurrent implantation failure.

Conclusion

OVGP1 is specifically induced in the luminal epithelium at the time of embryo implantation where it regulates receptivity-related genes and aids in trophoblast adhesion.

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Acknowledgements

We express our gratitude to Dr. Geetanjali Sachdeva for generously giving the Ishikawa and JAr cells. We are thankful to Mr. Abhishek Tiwari (intern at NIRRH) for the technical help. The present study (RA/597/01-2018) is funded by intra-mural grants from ICMR to DM and NMIMS (Deemed-to-be University) to PB.

Funding source

Indian Council of Medical Research (ICMR), Government of India; Department of Biotechnology, Government of India; and SVKM’s NMIMS (Deemed-to-be University).

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Authors and Affiliations

  1. Department of Biological Sciences, NMIMS Sunandan Divatia School of Science, NMIMS (Deemed-to-be University), Vile Parle (west), Mumbai, 400056, India

    Saniya Laheri & Purvi Bhatt

  2. Molecular and Cellular Biology Laboratory, ICMR-National Institute for Research in Reproductive Health, J. M. Street, Parel, Mumbai, 400012, India

    Nancy Ashary & Deepak Modi

Authors
  1. Saniya Laheri
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  2. Nancy Ashary
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  4. Deepak Modi
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Corresponding author

Correspondence to Deepak Modi.

Ethics declarations

The study was approved by the Institutional Animal Ethics Committee (IAEC) of the National Institute for Research in Reproductive (NIRRH).

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The authors declare that they have no conflict of interests.

Electronic supplementary material

Supplementary table 1

(DOCX 22 kb)

Supplementary Fig 1

Distribution of OVGP1 mRNA in different cell types of human endometrium. Data was extracted from GEO dataset accession no. GDS4987. In that study, endometrial cell types were separated using fluorescence-assisted cell sorting from proliferative stage endometrial biopsies and subjected microarray analysis. The values of the Y-axis are mean ± SEM of fold change. Fold change for each sample was calculated using mean values of epithelial cells taken as 1. The number of samples analyzed for each cell type is indicated (n). Each dot represents levels of OVGP1 in an individual. (PNG 168 kb)

Hig-resolution image (TIF 19 kb)

Supplementary Fig 2

mRNA expression of Ovgp1 in mouse endometrium at time of embryo implantation. Panel A is the representative gel image for Ovgp1, and panel B is the representative gel image for housekeeping gene Gapdh. The bands for Ovgp1 (185 bp) and Gapdh (179 bp) are shown by arrows. In both panels, lane 1 is the 100 bp ladder, lane 2 is the oviduct, lane 3 is the uterus at diestrus stage, lane 4 is the uterus on day 4 morning, lane 5 is the uterus on day 4 evening, lane 6 is the uterus on day 5 morning, (day of vaginal plus as day 1), and lane 7 is the negative control without template. (PNG 228 kb)

Hig-resolution image (TIF 46 kb)

Supplementary Fig 3

Cyclic changes in OVGP1 mRNA in human endometrium. Data was extracted from GEO dataset GDS2052. In this study, RNA from endometrial tissue from women at different stages of menstrual cycle were collected and subjected to microarray. The values of the Y-axis are mean ± SEM of fold change. Fold change for each sample was calculated using mean values of proliferative stage taken as 1. The number of samples analyzed for each stage of the menstrual cycle is indicated (n). Each point represents the levels of OVGP1 in an individual. (PNG 173 kb)

High-resolution image (TIF 19 kb)

Supplementary Fig 4

Levels of OVGP1 mRNA in the endometrium of women with recurrent implantation failure. The data was retrieved from GEO dataset accession no. GSE58144. In that study, endometrial biopsies were collected at mid-luteal phase from women undergoing IVF/ICSI. The control group consisted of a woman who conceived within first three IVF/ICSI cycles, whereas women with more than three failed IVF/ICSI treatment or replacement ≥ 10 embryos were categorized as recurrent implantation failure. The RNA was extracted and subjected to microarray. The values of the Y-axis are mean ± SEM of fold change. Fold change for each sample was calculated using mean values of control was taken as 1. The number of samples in each group is indicated (n). Each dot represents the levels of OVGP1 in an individual. (PNG 205 kb)

Hig-resolution image (TIF 19 kb)

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Laheri, S., Ashary, N., Bhatt, P. et al. Oviductal glycoprotein 1 (OVGP1) is expressed by endometrial epithelium that regulates receptivity and trophoblast adhesion. J Assist Reprod Genet 35, 1419–1429 (2018). https://doi.org/10.1007/s10815-018-1231-4

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