The prevalence of diabetes mellitus (DM) is about 6 % across the globe. This prevalence has been reported to increase in the near future. This means that the number of women with DM who would like to get pregnant and have children will also increase. The present study is aimed at investigating the morphological changes observed in the uterus after the onset of DM. The study also examined the pattern of distribution of nociceptin (NC), a neuropeptide involved in the regulation of pain, a major physiological factor during parturition. The study shows a severe atrophy of uteri as early as 15 days post DM and continued until the termination of the eight-week study. This atrophy was confirmed by light microscopy. Electron microscopy study showed atrophy of the columnar cells of the endometrium, reduced myofibril number and destruction of smooth muscle cells in the myometrium of diabetic rats compared to control. Immunofluorescence and immunoelectron microscopy studies clearly demonstrated the presence of NC in the endometrium, myometrium and on the myofibrils of the smooth muscles of both control and diabetic rat uteri. In addition, NC-positive neurons and varicose fibres were observed in the myometrium of both normal and diabetic rats. However, the expression of NC decreased after the onset of DM. Morphometric analysis showed that the number of NC-labeled cells was significantly (p < 0.05) lower in diabetic rat uteri compared to those of control. In conclusion, DM-induced uterine atrophy is associated with a decrease in the expression of NC in cells, neurons and myofibrils of the rat uterus.
Nociceptin Diabetics Uterus Neuropeptide Electron microscopy Immunofluorescence Atrophy
This is a preview of subscription content, log in to check access.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
Adeghate E, Ponery A (2004) Diabetes mellitus influences the degree of colocalization of calcitonin gene-related peptide with insulin and somatostatin in the rat pancreas. Pancreas 29:311–319PubMedCrossRefGoogle Scholar
Adeghate E, Hameed RS, Ponery AS et al (2010) Streptozotocin causes pancreatic beta cell failure via early and sustained biochemical and cellular alterations. Exp Clin Endocrinol Diabetes Off J Ger Soc Endocrinol Ger Diabetes Assoc 118:699–707. doi:10.1055/s-0030-1253395CrossRefGoogle Scholar
Berzetei-Gurske IP, Schwartz RW, Toll L (1996) Determination of activity for nociceptin in the mouse vas deferens. Eur J Pharmacol 302:R1–R2PubMedCrossRefGoogle Scholar
Chesterfield M, Janik J, Murphree E, Lynn C, Schmidt E, Callahan P (2006) Orphanin FQ/nociceptin is a physiological regulator of prolactin secretion in female rats. Endocrinology 147:5087–5093PubMedCrossRefGoogle Scholar
Dumont M, Lemaire S (1998) Characterization of the high affinity [3H] nociceptin binding site in membrane preparations of rat heart: correlations with the non-opioid dynorphin binding site. J Mol Cell Cardiol 30:2751–2760. doi:10.1006/jmcc.1998.0838PubMedCrossRefGoogle Scholar
Karnovsky MJ (1965) A formaldehyde-glutaraldehyde fixative of high osmolarity for use in electron microscopy. J Cell Biol 27:137–139Google Scholar
Kim S-J, Ju A, Lim S-G, Kim D-J (2013) Chronic alcohol consumption, type 2 diabetes mellitus, insulin-like growth factor-I (IGF-I), and growth hormone (GH) in ethanol-treated diabetic rats. Life Sci 93:778–782. doi:10.1016/j.lfs.2013.09.018PubMedCrossRefGoogle Scholar
Mollereau C, Mouledous L (2000) Tissue distribution of the opioid receptor-like (ORL1) receptor. Peptides 21:907–917PubMedCrossRefGoogle Scholar
Netti C, Rapetti D, Sibilia V et al (2002) Endocrine effects of centrally injected nociceptin in the rat. Brain Res 938:55–61PubMedCrossRefGoogle Scholar
Osinski MA, Brown DR (2000) Orphanin FQ/nociceptin: a novel neuromodulator of gastrointestinal function? Peptides 21:999–1005PubMedCrossRefGoogle Scholar
Osinski MA, Pampusch MS, Murtaugh MP, Brown DR (1999) Cloning, expression and functional role of a nociceptin/orphanin FQ receptor in the porcine gastrointestinal tract. Eur J Pharmacol 365:281–289PubMedCrossRefGoogle Scholar
Rizzi A, Calò G, Trevisani M et al (1999) Nociceptin receptor activation inhibits tachykinergic non adrenergic non cholinergic contraction of guinea pig isolated bronchus. Life Sci 64:PL157–PL163PubMedCrossRefGoogle Scholar
Sjostrand FS (1956) A method to improve contrast in high resolution electron microscopy of ultrathin tissue sections. Exp Cell Res 10:657–664PubMedCrossRefGoogle Scholar
Takahashi T, Bagnol D, Schneider D et al (2000) Orphanin FQ causes contractions via inhibiting purinergic pathway in the rat colon. Gastroenterology 119:1054–1063PubMedCrossRefGoogle Scholar
Taniguchi H, Yomota E, Nogi K et al (1998) The effect of nociceptin, an endogenous ligand for the ORL1 receptor, on rat colonic contraction and transit. Eur J Pharmacol 353:265–271PubMedCrossRefGoogle Scholar
Tatewaki R, Otani H, Tanaka O, Kitada J (1989) A morphological study on the reproductive organs as a possible cause of developmental abnormalities in diabetic NOD mice. Histol Histopathol 4:343–358PubMedGoogle Scholar
Tekes K, Hantos M, Gyenge M et al (2005) Diabetes and endogenous orphanin FQ/nociceptin levels in rat CSF and plasma. Int J Diabetes Metab 13:147–153Google Scholar
Wang JB, Johnson PS, Imai Y et al (1994) cDNA cloning of an orphan opiate receptor gene family member and its splice variant. FEBS Lett 348:75–79PubMedCrossRefGoogle Scholar