Angiotensin II induces apoptosis in human mural granulosa-lutein cells, but not in cumulus cells.
OBJECTIVE
To test whether angiotensin II (AngII) could modulate apoptosis of human granulosa-lutein (GL) cells from gonadotropin-stimulated follicles.


METHODS
In vitro assays on mural and cumulus granulosa cells.


METHODS
University laboratory and private IVF practice.


METHODS
One hundred six consecutive women undergoing 113 IVF cycles.


METHODS
Purified human GL mural or cumulus cells were cultured in serum-free media in the presence or absence of AngII with or without the AngII receptor blockers saralasin and CGP42112A.


METHODS
Detection of apoptosis using a fluorescent in situ marker for activated caspases.


RESULTS
Mural cells had approximately eightfold the amount of apoptosis compared with cumulus cells (average 0.23 vs. <0.03, respectively). With mural cells, AngII increased GL cell apoptosis versus untreated control samples (AngII 10(-)11 mol/L +6.5%; AngII 10(-9) mol/L +13.3%, and AngII 10(-7) mol/L +11.3%), an effect which was blocked by concurrent incubation with AngII receptor blockers. The AngII receptor blockers produced a significant decrease of apoptosis compared with control cultures (saralasin: 19.4%; CGP42112A: 28.9%). Neither AngII nor blockers had effect on cumulus cells.


CONCLUSIONS
Preovulatory concentrations of AngII, most likely via AT2 receptors, increase apoptosis of cultured mural GL cells but have no effect on cumulus cells. Granulosa cells appear to be differentially regulated by AngII.
Acosta
Elisa
E
Department of Biochemistry and Molecular Biology, University of La Laguna, Tenerife, Spain.
Peña
Oscar
O
Naftolin
Frederick
F
Avila
Julio
J
Palumbo
Angela
A
D000293:Adolescent; D000328:Adult; D000375:Aging / Q000502:physiology; D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D018929:Cell Culture Techniques; D016895:Culture Media, Serum-Free; D054885:Cumulus Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D005260:Female; D005307:Fertilization in Vitro; D005640:Follicle Stimulating Hormone / Q000097:blood; D006107:Granulosa Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008597:Menstrual Cycle; D010062:Ovulation Induction; D018579:Patient Selection; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
D047228:Angiotensin II Type 1 Receptor Blockers; D016895:Culture Media, Serum-Free; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D005640:Follicle Stimulating Hormone