Expression of the progesterone receptor, bcl-2 and bax in clomiphene citrate treated rat uteri
Year: 2011
Type: dissertation
Abstract: Clomiphene citrate (CC) is a synthetic oestrogen receptor modulator that may act \nto promote or inhibit oestrogenic responses depending on the type of tissue or \norganism. CC acts as a superovulator and has been widely prescribed in the \ntreatment of female infertility. However, pregnancy rates after CC treatment are \nlow, possibly due to the CC causing morphological and other unidentified changes \nto the uterus. \nThis study investigated the changes caused by CC on the progesterone receptor \n(PR), the anti-apoptotic protein, Bcl-2, and the pro-apoptotic protein, Bax. \nPR with its ligand, progesterone, is important for the maintenance of a pregnancy. \nBcl-2 is a cell survival molecule and acts in opposition to Bax, which promotes \napoptosis, which is important in allowing an attaching blastocyst to infiltrate the \nmaternal endometrium. \nA high physiological dose of CC (1.25 mg) was administered to ovariectomised \nrats, either as a single treatment, or prior to a hormonal treatment regime \ncharacteristic of pre-implantation animals. The single CC treated animals were \ncompared with single 5 mg progesterone (P4) treated animals and vehicle controls. \nThe animals treated with CC in conjunction with the ovarian hormone milieu \n(CCPPPE treatment) were compared to PPPE treated animals or to the vehicle \ncontrols. \nThe effects of CC, P4, PPPE and SPPPE on the morphology of the uteri were \ninvestigated by light microscopy. Expression of the PR, Bcl-2 and Bax were \ninvestigated using immunohistochemistry and enzyme linked immunosorbent \n(ELISA) techniques. \nThe present study showed that CC treatment affects the microanatomy of the \nuterine compartments, particularly the shape of the lumen and the luminal \nepithelial height. The expressions of PR, Bcl-2 and Bax in the entire uterus were not significantly affected by the various treatments applied to the ovariectomised \nrats, as measured using ELISA. However, expression of the proteins in the various \nuterine compartments was altered by CC treatment. The single CC and CCPPPE \ntreatments had an oestrogenic effect with regards to PR expression in the uteri as \nseen in the immunolocalisation, whereas the single P4 treatment decreased the PR \nexpression, as expected. CC treatment caused patchiness in both Bcl-2 and Bax \nexpression surrounding the endometrial lumen. Moreover, treatment with CC \nmaintained expression of Bcl-2 in the luminal epithelium, whereas the expression \nof Bax shifted away from the luminal epithelium. This suggests that CC treatment \npromotes cell survival of the luminal epithelium, which may diminish the ability \nof the blastocyst to infiltrate the maternal tissue. \nCC action is both dose sensitive and has a cumulative effect with multiple \ntreatments. Future studies would aim to separate the various uterine compartments \nin order to quantitatively assess the actions of CC on expression in the PR, Bcl-2 \nand Bax. In addition, it would be interesting to investigate how the accumulation \nof subsequent CC doses affects the expression of apoptotic markers, as this would \nbe a more realistic model for human infertility treatment.
Author: Thérèse Dix‐Peek
Language: English
Subfield: Endocrinology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2287465845