Peroxisome proliferator–activated receptor-gamma induces regression of endometrial explants in a rat model of endometriosis

Lebovic, Dan I.; Kır, Mustafa; Casey, Colleen

doi:10.1016/j.fertnstert.2004.02.148

Cited by 121 publications

(83 citation statements)

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“…Several in vitro studies with thiazolidinediones (TZDs) and endometriotic cells (15,39) led to their use in endometriosis animal models. To date there have been two published studies using TZDs in the rat model of endometriosis with one revealing decreased induction of lesions (51) and another showing regression of established disease (19). Since rodents do not have menses or develop spontaneous endometriosis, the ectopic autologous transplantation of uterine tissue in this model (52) may not sufficiently replicate human endometriosis.…”

Section: Discussionmentioning

confidence: 99%

“…PPAR-γ ligands have been shown to decrease aromatase activity in cultured human granulosa cells (18). We published our study using a PPAR-γ agonist, ciglitazone, in the rat model of endometriosis to evaluate a new approach to immunomodulation of endometriosis (19). The uterine autograft from ciglitazonetreated rats showed marked epithelial changes and overall regression of the explant.…”

Section: Introductionmentioning

confidence: 97%

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PPAR-gamma receptor ligand induces regression of endometrial explants in baboons: A prospective, randomized, placebo- and drug-controlled study

Lebovic

Mwenda

Chai

et al. 2007

Fertility and Sterility

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Objective-To determine the effects of a thiazolidinedione (TZD) agonist of peroxisome proliferator-activated receptor (PPAR)-γ, rosiglitazone, in a baboon model of established endometriosis.Design-Prospective, randomized, placebo-controlled study.Setting-Experimental surgery laboratory at the Institute of Primate Research in Nairobi, Kenya.Animal(s)-Endometriosis was induced using intrapelvic injection of eutopic menstrual endometrium in 12 female baboons with a normal pelvis that had undergone at least one menstrual cycle since the time of captivity.Intervention(s)-Induction of endometriosis by laparoscopy was performed in 12 baboons with a normal pelvis. Endometrial tissue was extracted from each baboon by curettage and a standard amount of endometrium was then seeded onto several peritoneal sites as previously described. About 34-68 days after the induction of laparoscopy, a pre-treatment laparoscopy (baseline disease assessment) was performed in the baboons to record the extent of endometriotic lesions. The 12 baboons were randomized into 3 groups and treated from the day after the staging laparoscopy for a total duration of 30 days. They received either PBS tablets (n=4, placebo control; placebo tablets once a day by mouth for 30 days), GnRH-antagonists (n=4, active control; Ganirelix acetate 125 μg/day for 30 days) or rosiglitazone (n=4, test drug, 2 mg by mouth each day for 30 days). A 3 rd and final laparoscopy on day 30 after the start of treatment was performed to record the extent of endometriosis. The type of lesion (typical, red, white and suspicious) was recorded. Biopsies were obtained to confirm the histological presence of endometriosis.Main Outcome Measure(s)-A videolaparoscopy was performed 30 days after treatment to document the number and surface area of endometriotic lesions as well as to calculate the revised American Society for Reproductive Medicine score (rAFS) and stage.Corresponding author Dan I. Lebovic, M.D., M.A., Department of Obstetrics and Gynecology, University of Michigan, Tel: 734-615-8257, Fax: 734-647-1006, E-mail: lebovic@umich.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

PPAR-gamma receptor ligand induces regression of endometrial explants in baboons: A prospective, randomized, placebo- and drug-controlled study

Lebovic

Mwenda

Chai

et al. 2007

Fertility and Sterility

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“…Although these mice had a normal number of follicles and developed corpora lutea, progesterone (P 4 ) level was reduced, implantation rates were lower and litters were smaller [19]. An administration of PPARg agonist for 4 weeks did not affect folliculogenesis, but increased plasma P 4 concentration [27]. There is a lack of similar studies on the tissue-specific deletion of the two remaining PPAR isoforms.…”

Section: Ppars In the Ovarymentioning

confidence: 99%

Peroxisome proliferator-activated receptors in the regulation of female reproductive functions

Bogacka

Kurzyńska

Bogacki

et al. 2015

Folia Histochem Cytobiol.

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Peroxisome proliferator-activated receptors (PPARs) belong to a ligand-dependent nuclear receptor family. In the past decade, numerous studies have revealed the presence and significance of PPARs in the reproductive system. PPARs are expressed at different levels of hypothalamic-pituitary-gonadal (HPG) axis. They are also present in the uterus as well as in the placenta and embryonic tissues of different species. PPARs significance has been reported during the estrous/menstrual cycle and pregnancy with the gamma isoform studied most frequently. Several studies indicate that PPARs regulate proliferation of ovarian cells, tissue remodeling and steroidogenesis. In the endometrium, PPARs are engaged in the regulation of prostaglandins, steroids and cytokines synthesis. The role of PPARs in the trophoblast differentiation, maturation and invasion as well as in the embryo development has also been demonstrated. In this review, we summarize current findings concerning the role of PPARs in the regulation of reproductive functions at different levels of the HPG axis during various physiological statuses of females. In addition, the role of PPARs in the modulation of uterine functions as well as the placenta and embryo development has also been discussed.

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“…Instead, it results from a decrease in the number of embryos implanted, and this, in turn, probably results from a decrease in progesterone secretion by the corpus luteum (Cui et al 2002). Furthermore, 4 weeks of ciglitazone injection in rats did not modify folliculogenesis, but did increase serum progesterone concentration (Lebovic et al 2004). Thus, PPAR seems to play a significant role in fertility control.…”

Section: Ppar Action In Corpus Luteummentioning

confidence: 99%

Peroxisome proliferator-activated receptors in reproductive tissues: from gametogenesis to parturition

Froment¹,

Gizard²,

Defever³

et al. 2006

Journal of Endocrinology

180

132

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Peroxisome proliferator–activated receptor-gamma induces regression of endometrial explants in a rat model of endometriosis

Cited by 121 publications

References 38 publications

PPAR-gamma receptor ligand induces regression of endometrial explants in baboons: A prospective, randomized, placebo- and drug-controlled study

PPAR-gamma receptor ligand induces regression of endometrial explants in baboons: A prospective, randomized, placebo- and drug-controlled study

Peroxisome proliferator-activated receptors in the regulation of female reproductive functions

Peroxisome proliferator-activated receptors in reproductive tissues: from gametogenesis to parturition

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