Bcl-2, Fas and caspase 3 expression in endometrium from levonorgestrel implant users with and without breakthrough bleeding

• Published in: Human reproduction (Oxford) Vol. 15; no. suppl-3; pp. 152 - 161
• Main Authors: Rogers, Peter A.W., Lederman, Fiona, Plunkett, Debbie, Affandi, Biran
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Oxford Oxford University Press 01.08.2000
• Subjects: Apoptosis; Bcl-2; Biological and medical sciences; Caspase 3; Caspases - analysis; Contraceptive Agents, Female - adverse effects; Drug Implants; Drug toxicity and drugs side effects treatment; endometrium; Endometrium - chemistry; Endometrium - pathology; Fas; fas Receptor - analysis; Female; Humans; Immunohistochemistry; Levonorgestrel - adverse effects; Medical sciences; Norplant; Pharmacology. Drug treatments; Progesterone Congeners - adverse effects; Proto-Oncogene Proteins c-bcl-2 - analysis; Tissue Distribution; Toxicity: urogenital system; Uterine Hemorrhage - chemically induced; Uterine Hemorrhage - metabolism; Uterine Hemorrhage - pathology; Bcl-2; endometrium; Fas; caspase 3; Norplant; Human; Immunohistochemistry; Menstruation disorders; Menstruation; Menstrual cycle; Implant; Toxicity; Levonorgestrel; Gene expression; Progestagen; Uterus; Cell death; C-Onc gene; Female genital system; Female; Contraceptive; Endometrium; Protooncogene; Apoptosis
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/15.suppl_3.152

Women using the progestin-only contraceptive Norplant® often suffer from unpredictable bouts of breakthrough bleeding, which usually occurs from a thin atrophic endometrium. The role of cellular apoptosis in the endometrial response to Norplant has not been investigated. The aim of the present study was to use immunohistochemistry to produce semi-quantitative scores for expression of the apoptosis-related proteins Bcl-2, Fas and caspase 3 in endometrium from 16 controls and 42 women using Norplant with minimal or major breakthrough bleeding problems. The results showed no difference in endometrial immunostaining for any of the three proteins between Norplant users with and without breakthrough bleeding. There was also no evidence of endometrial endothelial cell immunostaining for any of the proteins. Bcl-was the only protein to show a cyclical pattern, with higher expression in the proliferative compared to secretory glands. All three proteins showed different expression levels in control functionalis versus basalis, with the survival protein Bcl-2 being higher in basalis, and the death receptor Fas and the proteolytic enzyme caspase 3 being higher in the functionalis. Overall, the results suggest that apoptosis is regulated differently in functionalis compared to basalis, and that atrophic Norplant-exposed endometrium appears more like functionalis than basalis with respect to expression of Fas and caspase 3. There was no evidence for a role for apoptosis in the mechanisms that underlie progestininduced endometrial breakthrough bleeding.