Gulcin Sahin Ersoy, Meryem Kurek Eken, Ozge Cevik, Ozlem T

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Mycophenolate mofetil attenuates uterine ischaemia/reperfusion injury in a rat model Gulcin Sahin Ersoy, Meryem Kurek Eken, Ozge Cevik, Ozlem T. Cilingir, Reshef Tal Reproductive BioMedicine Online Volume 34, Issue 2, Pages 115-123 (February 2017) DOI: 10.1016/j.rbmo.2016.11.007 Copyright © 2016 Reproductive Healthcare Ltd. Terms and Conditions

Figure 1 The concentrations of 8-hydroxy-2′-deoxyguanosine (8-OHdG), ischaemia modified albumin (IMA), glutathione (GSH), malondialdehyde (MDA), myeloperoxidase (MPO) and superoxide dismutase (SOD), in the sham + vehicle (C), sham + MMF (M), ischaemia/reperfusion + vehicle (I/R + V) and I/R + mycophenolate mofetil (I/R + M) treated groups. Values are expressed as mean ± SD (n = 7 rats in each group). *P < 0.05, **P < 0.01, ***P < 0.001 versus C group; †P < 0.05, ††P < 0.01, †††P < 0.001 versus M group; #P < 0.05, ##P < 0.01, ###P < 0.001 versus IR + V group. Reproductive BioMedicine Online 2017 34, 115-123DOI: (10.1016/j.rbmo.2016.11.007) Copyright © 2016 Reproductive Healthcare Ltd. Terms and Conditions

Figure 2 Histological micrographs of haematoxylin-eosin stained uteri following ischaemia/reperfusion (I/R) injury. (a) Sham + vehicle group. Epithelial cell layer with regular morphology (arrow); normally organized uterine glands (arrowhead); endometrial stroma without cellular infiltrates (E). (b) Sham + MMF group. Epithelial cell layer with regular morphology (arrow); normally organized uterine glands (arrowhead). (c) I/R + vehicle (V) group. Surface epithelium with raised height (black arrow) and increased number of cell layers (white arrow); polymorphonuclear cell infiltration (white arrowhead) into oedematous endometrial stroma (E); congested blood vessels (asterisks); uterine glands showing epithelial cells with cytoplasm loss (black arrowhead). (d) I/R + mycophenolate mofetil (M) group demonstrating abnormally organized surface epithelium (arrow) but less irregularity of uterine glands (black arrowhead), blood vessels with milder vasocongestion (asterisks) and less polymorphonuclear cell infiltration (white arrow) into endometrial stroma (E) compared with I/R + V group; myometrium with regular morphology (M). Reproductive BioMedicine Online 2017 34, 115-123DOI: (10.1016/j.rbmo.2016.11.007) Copyright © 2016 Reproductive Healthcare Ltd. Terms and Conditions

Figure 3 Micrographs of TUNEL-stained paraffin sections (a, d, g, j) and toluidine blue-stained semi-thin Epon sections (b, e, h, k) at light microscopic level, and contrasted thin sections at electron microscopic level (c, f, i, l) of rat uterine tissue. Control sham groups (a–f); regular contour of endometrial epithelium (arrows), glands (arrowheads) and stroma (asterisks). ischaemia/reperfusion + vehicle (I/R + V) group (g–i) demonstrating numerous TUNEL-positive cells in epithelium (g, arrows) and glands (g, arrowhead) along with glandular degeneration (h, arrowheads). Vacuolization in cytoplasm of endometrial epithelial cells (h, E) and glandular cells was also noted (i, V). I/R + mycophenolate mofetil (M) group (j–l) showing less TUNEL-positive staining in endometrial epithelium (j, arrow) and glands (j, arrowhead), and regular organization of uterine stroma (j and k, asterisks) and glands (k, arrowhead) without cytoplasmic vacuolization (l). Reproductive BioMedicine Online 2017 34, 115-123DOI: (10.1016/j.rbmo.2016.11.007) Copyright © 2016 Reproductive Healthcare Ltd. Terms and Conditions

Figure 4 TUNEL scoring in the sham + vehicle (C), sham + mycophenolate mofetil (M), ischaemia/reperfusion + vehicle (I/R + V) and ischaemia-reperfusion + mycophenolate mofetil (I/R + M) groups. **P < 0.01 versus C group; ††P < 0.01 versus M group; ##P < 0.01 versus IR + V group. Reproductive BioMedicine Online 2017 34, 115-123DOI: (10.1016/j.rbmo.2016.11.007) Copyright © 2016 Reproductive Healthcare Ltd. Terms and Conditions