Role of macrophage secretions on rat polycystic ovary: its effect on apoptosis.
Polycystic ovarian syndrome is the most common endocrine disorder among women of reproductive age. Little is known about its etiology, although the evidence suggests an intrinsic ovarian abnormality in which endocrine, metabolic, neural and immune factors would be involved. In this work, the effects of macrophage (MO) secretion on ovarian apoptosis in a polycystic ovary syndrome rat model (PCO rat) induced by estradiol valerate are studied. Spleen MO secretions were used to stimulate ovaries and ovarian interstitial and granulosa cells from both PCO and control rats. Ovarian hormones and prostaglandin E2 (PGE2) were measured by RIA; ovarian mRNA levels of Bax, Bcl2 and NFkB by RT-PCR; and ovarian inducible nitric oxide synthase (iNOS) by western blot. The number of apoptotic cells was evaluated by TUNEL. In the PCO ovary, the MO secretions from PCO rats increased the Bax and NFkB mRNA expressions and increased TUNEL staining in both granulosa and theca cells. In addition, the PCO MO secretions produced a decrease of nitric oxide release, iNOS protein level and PGE2 content in the PCO ovary, and it also induced an increase of androstenedione production by PCO interstitial cells, in comparison with control MO secretions. Considering these results and knowing that testosterone stimulates tumour necrosis factor-α production by PCO MO modifying ovarian response by increasing androstenedione, it is reasonable to suggest that the increase of androgens stimulated in ovarian cells by PCO MO secretions could in turn stimulate the cytokine production from MO, thus maintaining an apoptotic vicious cycle in the PCO ovary.
Laboratorio de Biología de la ReproducciónyÁrea MorfologíaDepartamento de Bioquímica y Ciencias Biológicas, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, ArgentinaLaboratorio de Fisio-patología Ovárica (CEFYBO)Universidad de Buenos Aires, Argentina.
Florencia
F
Figueroa
Laboratorio de Biología de la ReproducciónyÁrea MorfologíaDepartamento de Bioquímica y Ciencias Biológicas, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, ArgentinaLaboratorio de Fisio-patología Ovárica (CEFYBO)Universidad de Buenos Aires, Argentina.
Alicia
A
Motta
Laboratorio de Biología de la ReproducciónyÁrea MorfologíaDepartamento de Bioquímica y Ciencias Biológicas, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, ArgentinaLaboratorio de Fisio-patología Ovárica (CEFYBO)Universidad de Buenos Aires, Argentina.
Mariano
M
Acosta
Laboratorio de Biología de la ReproducciónyÁrea MorfologíaDepartamento de Bioquímica y Ciencias Biológicas, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, ArgentinaLaboratorio de Fisio-patología Ovárica (CEFYBO)Universidad de Buenos Aires, Argentina.
Fabian
F
Mohamed
Laboratorio de Biología de la ReproducciónyÁrea MorfologíaDepartamento de Bioquímica y Ciencias Biológicas, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, ArgentinaLaboratorio de Fisio-patología Ovárica (CEFYBO)Universidad de Buenos Aires, Argentina.
Liliana
L
Oliveros
Laboratorio de Biología de la ReproducciónyÁrea MorfologíaDepartamento de Bioquímica y Ciencias Biológicas, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, ArgentinaLaboratorio de Fisio-patología Ovárica (CEFYBO)Universidad de Buenos Aires, Argentina mlforneris@gmail.com.
Myriam
M
Forneris
D000735:Androstenedione / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D003270:Contraceptive Agents / Q000633:toxicity; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004958:Estradiol / Q000031:analogs & derivatives / Q000633:toxicity; D005260:Female; D007124:Immunoenzyme Techniques; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
C494828:Bax protein, rat; D003270:Contraceptive Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D009569:Nitric Oxide; D000735:Androstenedione; D004958:Estradiol; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D015232:Dinoprostone