{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T23:21:36Z","timestamp":1773098496023,"version":"3.50.1"},"reference-count":36,"publisher":"CSIRO Publishing","issue":"9","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":3745,"URL":"https:\/\/doi.org\/10.1071\/journalslicense"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,7,21]]},"abstract":"<jats:p>During the oestrous cycle canine endometrium undergoes cyclical cellular proliferation, apoptosis and differentiation. To study the regulation of endometrial apoptosis and proliferation events the expression of apoptosis-related genes was analysed by real-time polymerase chain reaction and cellular expression of their proteins was identified through immunohistochemistry. Cellular apoptosis and proliferation events were detected by TdT-mediated dUTP-biotin nick end labeling (TUNEL) and proliferation marker Ki67 immunostaining, respectively. The highest proliferative index was observed in the follicular phase (all endometrial cellular components) and at early dioestrus (basal glands). This was associated with a low apoptotic index and a strong expression of anti- (Bcl2) and pro-apoptotic proteins (Fas, FasL, Bax). Subsequently (Days 11\u201345 of dioestrus), basal glandular epithelium experienced the highest apoptotic index, coincidental with a decrease of Bcl2 expression and a low ratio of Bcl2\/Bax transcription. An increase in the apoptotic index of crypts, stromal and endothelial cells was observed at late dioestrus and the beginning of anoestrus. These results indicate that pro- and anti-apoptotic proteins regulate the balance between cell proliferation and death in the canine endometrium during the oestrous cycle. High Bcl2 expression in both the follicular and early dioestrous phases stimulate glandular proliferation and prevent apoptosis but, in the non-pregnant uterus, a decrease in Bcl2 expression together with an increase in pro-apoptotic proteins induces apoptosis of basal glandular epithelium cells.<\/jats:p>","DOI":"10.1071\/rd14245","type":"journal-article","created":{"date-parts":[[2015,2,23]],"date-time":"2015-02-23T23:03:36Z","timestamp":1424732616000},"page":"1307-1317","source":"Crossref","is-referenced-by-count":3,"title":["Oestrous cycle-dependent expression of Fas and Bcl2 family gene products in normal canine endometrium"],"prefix":"10.1071","volume":"28","author":[{"given":"S.","family":"Henriques","sequence":"first","affiliation":[{"name":"ACIISA, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade T\u00e9cnica, 1300-477 Lisboa, Portugal."}]},{"given":"E.","family":"Silva","sequence":"additional","affiliation":[{"name":"ACIISA, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade T\u00e9cnica, 1300-477 Lisboa, Portugal."}]},{"given":"S.","family":"Cruz","sequence":"additional","affiliation":[{"name":"ACIISA, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade T\u00e9cnica, 1300-477 Lisboa, Portugal."}]},{"given":"M. F.","family":"Silva","sequence":"additional","affiliation":[{"name":"ACIISA, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade T\u00e9cnica, 1300-477 Lisboa, Portugal."}]},{"given":"G.","family":"Ferreira-Dias","sequence":"additional","affiliation":[{"name":"ACIISA, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade T\u00e9cnica, 1300-477 Lisboa, Portugal."}]},{"given":"L.","family":"Lopes-da-Costa","sequence":"additional","affiliation":[{"name":"ACIISA, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade T\u00e9cnica, 1300-477 Lisboa, Portugal."}]},{"given":"L.","family":"Mateus","sequence":"additional","affiliation":[{"name":"ACIISA, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade T\u00e9cnica, 1300-477 Lisboa, Portugal."},{"name":"BCorresponding author. Email: lmateus@fmv.ulisboa.pt"}]}],"member":"67","published-online":{"date-parts":[[2015,2,24]]},"reference":[{"key":"2025102820032146400_R1","unstructured":"Applied Biosystems (2003). Creating standard curves with genomic DNA or plasmid DNA templates for use in quantitative PCR. Available from: http:\/\/www6.appliedbiosystems.com\/support\/tutorials\/pdf\/quant_pcr.pdf [Verified 6 February 2015]."},{"key":"2025102820032146400_R2","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.1016\/J.THERIOGENOLOGY.2006.01.018","article-title":"Degeneration and apoptosis of endometrial cells in the bitch.","volume":"66","author":"Chu","year":"2006","journal-title":"Theriogenology"},{"key":"2025102820032146400_R3","doi-asserted-by":"crossref","first-page":"64","DOI":"10.2460\/ajvr.1989.50.01.64","article-title":"Concentration of receptors for oestradiol and progesterone in canine endometrium during oestrus and dioestrus.","volume":"50","author":"Fernandes","year":"1989","journal-title":"Am. J. Vet. Res."},{"key":"2025102820032146400_R4","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1046\/J.1439-0531.2003.00459.X","article-title":"Morphological changes of endometrial epithelium in the bitch during metoestrus and anoestrus.","volume":"38","author":"Galabova","year":"2003","journal-title":"Reprod. Domest. Anim."},{"key":"2025102820032146400_R5","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1530\/JRF.0.1160167","article-title":"Cell proliferation patterns in the equine endometrium throughout the non-pregnant reproductive cycle.","volume":"116","author":"Gerstenberg","year":"1999","journal-title":"J. Reprod. Fertil."},{"key":"2025102820032146400_R6","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1006\/METH.2001.1261","article-title":"An overview of real-time quantitative PCR: applications to quantify cytokine gene expression.","volume":"25","author":"Giulietti","year":"2001","journal-title":"Methods"},{"key":"2025102820032146400_R7","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1016\/J.THERIOGENOLOGY.2009.11.019","article-title":"Endometrial cytology and computerised morphometric analysis of epithelial nuclei: a useful tool for reproductive diagnosis in the bitch.","volume":"73","author":"Groppetti","year":"2010","journal-title":"Theriogenology"},{"key":"2025102820032146400_R8","doi-asserted-by":"publisher","first-page":"11 962","DOI":"10.1074\/JBC.270.20.11962","article-title":"Structure\u2013function analysis of Bcl2 protein. Identification of conserved domains important for homodimerisation with Bcl2 and heterodimerisation with Bax.","volume":"270","author":"Hanada","year":"1995","journal-title":"J. Biol. Chem."},{"key":"2025102820032146400_R9","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1093\/HUMUPD\/DMH007","article-title":"Apoptosis in human endometrium and endometriosis.","volume":"10","author":"Harada","year":"2004","journal-title":"Hum. Reprod. Update"},{"key":"2025102820032146400_R10","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/J.THERIOGENOLOGY.2009.08.002","article-title":"Epidermal growth factor, transforming growth factor-a and epidermal growth factor receptor expression and localisation in the canine endometrium during the oestrous cycle and in bitches with pyometra.","volume":"73","author":"Kida","year":"2010","journal-title":"Theriogenology"},{"key":"2025102820032146400_R11","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1111\/J.1439-0531.2012.02021.X","article-title":"Expression of survinin, Bcl2 and Bax proteins in the domestic cat (Felis catus) endometrium during the oestrus cycle.","volume":"48","author":"Liman","year":"2013","journal-title":"Reprod. Domest. Anim."},{"key":"2025102820032146400_R12","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1262\/JRD.18139","article-title":"Apoptosis in the porcine uterine endometrium during the oestrous cycle, early pregnancy and post partum.","volume":"53","author":"Okano","year":"2007","journal-title":"J. Reprod. Dev."},{"key":"2025102820032146400_R13","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/0092-8674(93)90509-O","article-title":"Bcl-2 heterodimerises in vivo with a conserved homolog BAX, that accelerates programmed cell death.","volume":"74","author":"Oltvai","year":"1993","journal-title":"Cell"},{"key":"2025102820032146400_R14","doi-asserted-by":"publisher","first-page":"1957","DOI":"10.1016\/S0093-691X(02)00644-1","article-title":"Comparisons of oestradiol, LH and FSH patterns in pregnant and non-pregnant beagle bitches.","volume":"57","author":"Onclin","year":"2002","journal-title":"Theriogenology"},{"key":"2025102820032146400_R15","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1007\/S007950100011","article-title":"Apoptosis in human endometrium: apoptotic detection methods and signalling.","volume":"34","author":"Otsuki","year":"2001","journal-title":"Med. Electron Microsc."},{"key":"2025102820032146400_R16","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/S0140-6736(94)91051-0","article-title":"Cyclic Bcl2 gene expression in human uterine endometrium during menstrual cycle.","volume":"344","author":"Otsuki","year":"1994","journal-title":"Lancet"},{"key":"2025102820032146400_R17","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/0145-2126(95)00135-2","article-title":"A day in the life of the Bcl-2 protein: does the turnover rate of Bcl-2 serve as a biological clock for cellular lifespan regulation?","volume":"20","author":"Reed","year":"1996","journal-title":"Leuk. Res."},{"key":"2025102820032146400_R18","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1002\/BDRB.20121","article-title":"Oestrous cycle-dependent histology and review of sex steroid receptor expression in dog reproductive tissues and mammary gland and associated hormone levels.","volume":"80","author":"Rehm","year":"2007","journal-title":"Birth Defects Res. B Dev. Reprod. Toxicol."},{"issue":"6","key":"2025102820032146400_R19","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1111\/RDA.12063","article-title":"Is apoptosis a regulatory mechanism during early canine pregnancy?","volume":"47","author":"Sch\u00e4fer-Somi","year":"2012","journal-title":"Reprod. Domest. Anim."},{"issue":"17","key":"2025102820032146400_R20","doi-asserted-by":"publisher","first-page":"7834","DOI":"10.1073\/PNAS.92.17.7834","article-title":"Multiple Bcl2 family members demonstrate selective dimerisations with BAX.","volume":"92","author":"Sedlak","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025102820032146400_R21","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1095\/BIOLREPROD65.4.979","article-title":"Regulation of Fas ligand expression by oestradiol and progesterone in human endometrium.","volume":"65","author":"Selam","year":"2001","journal-title":"Biol. Reprod."},{"key":"2025102820032146400_R22","doi-asserted-by":"crossref","first-page":"289","DOI":"10.56808\/2985-1130.2312","article-title":"Investigation of the relationship between endometrial MMP activities and sex hormones in mature bitches.","volume":"41","author":"Shia","year":"2011","journal-title":"Thai. J. Vet. Med."},{"key":"2025102820032146400_R23","first-page":"2251","article-title":"Bcl2 expression prevents activation of the ICE protease cascade.","volume":"12","author":"Shimizu","year":"1996","journal-title":"Oncogene"},{"key":"2025102820032146400_R24","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/J.JRI.2012.07.003","article-title":"Canine endometrial changes in toll-like receptors and prostaglandin production throughout the oestrous cycle.","volume":"96","author":"Silva","year":"2012","journal-title":"J. Reprod. Immunol."},{"key":"2025102820032146400_R25","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1093\/MOLEHR\/8.5.447","article-title":"Hormonal regulation of apoptosis and Fas and Fasl system in human endometrial cells.","volume":"8","author":"Song","year":"2002","journal-title":"Mol. Hum. Reprod."},{"key":"2025102820032146400_R26","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/S0014-4827(02)00056-3","article-title":"Compartmentalisation of Fas and Fas ligand may prevent auto- or paracrine apoptosis in epithelial cells.","volume":"284","author":"Tan","year":"2003","journal-title":"Exp. Cell Res."},{"key":"2025102820032146400_R27","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/NM0396-317","article-title":"Fas ligand in human serum.","volume":"2","author":"Tanaka","year":"1996","journal-title":"Nat. Med."},{"key":"2025102820032146400_R28","first-page":"2738","article-title":"Differential expression of members of the Bcl-2 gene family in proliferative and secretory human endometrium: glandular epithelial cell apoptosis is associated with increased expression of Bax.","volume":"82","author":"Tao","year":"1997","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2025102820032146400_R29","doi-asserted-by":"publisher","first-page":"1595","DOI":"10.1016\/S0093-691X(03)00178-X","article-title":"Apoptosis in the canine endometrium during the oestrous cycle.","volume":"60","author":"Van Cruchten","year":"2003","journal-title":"Theriogenology"},{"key":"2025102820032146400_R30","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/J.THERIOGENOLOGY.2003.11.015","article-title":"Proliferation patterns in the canine endometrium during the oestrous cycle.","volume":"62","author":"Van Cruchten","year":"2004","journal-title":"Theriogenology"},{"key":"2025102820032146400_R31","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/S0303-7207(00)00261-6","article-title":"Apoptosis and apoptosis-related proteins in human endometrium.","volume":"165","author":"Vaskivuo","year":"2000","journal-title":"Mol. Cell. Endocrinol."},{"key":"2025102820032146400_R32","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1016\/S0093-691X(99)00022-9","article-title":"Immunohistochemical detection of oestrogen receptors in the canine uterus and their relation to sex-steroid hormone levels.","volume":"51","author":"Vermeirsch","year":"1999","journal-title":"Theriogenology"},{"key":"2025102820032146400_R33","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1016\/S0093-691X(99)00273-3","article-title":"Immunohistochemical detection of progesterone receptors in the canine uterus and their relation to sex-steroid hormone levels.","volume":"53","author":"Vermeirsch","year":"2000","journal-title":"Theriogenology"},{"key":"2025102820032146400_R34","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1016\/S0002-9378(97)70499-X","article-title":"Bcl2 and Fas expression in eutopic and ectopic human endometrium during the menstrual cycle in relation to endometrial cell apoptosis.","volume":"176","author":"Watanabe","year":"1997","journal-title":"Am. J. Obstet. Gynecol."},{"key":"2025102820032146400_R35","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1002\/MRD.20215","article-title":"Fas, FasL, Bcl2 and Bax in the endometrium of Rhesus monkey during the menstrual cycle.","volume":"70","author":"Wei","year":"2005","journal-title":"Mol. Reprod. Dev."},{"key":"2025102820032146400_R36","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1093\/MOLEHR\/5.4.358","article-title":"Fas ligand, Fas antigen and Bcl2 expression in human endometrium during the menstrual cycle.","volume":"5","author":"Yamashita","year":"1999","journal-title":"Mol. Hum. Reprod."}],"container-title":["Reproduction, Fertility and Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/connectsci.au\/rd\/article-pdf\/28\/9\/1307\/315035\/rd14245.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/connectsci.au\/rd\/article-pdf\/28\/9\/1307\/315035\/rd14245.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:03:36Z","timestamp":1761696216000},"score":1,"resource":{"primary":{"URL":"https:\/\/connectsci.au\/rd\/article\/28\/9\/1307\/50469\/Oestrous-cycle-dependent-expression-of-Fas-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,24]]},"references-count":36,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2016,7,21]]}},"URL":"https:\/\/doi.org\/10.1071\/rd14245","relation":{},"ISSN":["1031-3613","1448-5990"],"issn-type":[{"value":"1031-3613","type":"print"},{"value":"1448-5990","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,2,24]]}}}