title: The local effects of ovarian diathermy in an ovine model of polycystic ovary syndrome.
abstract: In order to develop a medical alternative to surgical ovarian diathermy (OD) in polycystic ovary syndrome (PCOS) more mechanistic information is required about OD. We therefore studied the cellular, molecular and vascular effects of diathermy on the ovary using an established ovine model of PCOS. Pregnant sheep were treated twice weekly with testosterone propionate (100 mg) from day 30-100 gestation. Their female offspring (n = 12) were studied during their second breeding season when the PCOS-like phenotype, with anovulation, is fully manifest. In one group (n = 4) one ovary underwent diathermy and it was collected and compared to the contralateral ovary after 24 hours. In another group a treatment PCOS cohort underwent diathermy (n = 4) and the ovaries were collected and compared to the control PCOS cohort (n = 4) after 5 weeks. Ovarian vascular indices were measured using contrast-enhanced ultrasound and colour Doppler before, immediately after, 24 hours and five weeks after diathermy. Antral follicles were assessed by immunohistochemistry and ovarian stromal gene expression by quantitative RT-PCR 24 hours and 5 weeks after diathermy. Diathermy increased follicular atresia (P<0.05) and reduced antral follicle numbers after 5 weeks (P<0.05). There was an increase in stromal CCL2 expression 24 hours after diathermy (P<0.01) but no alteration in inflammatory indices at 5 weeks. Immediately after diathermy there was increased microbubble transit time in the ovarian microvasculature (P = 0.05) but this was not seen at 24 hours. However 24 hours after diathermy there was a reduction in the stromal Doppler blood flow signal (P<0.05) and an increased ovarian resistance index (P<0.05) both of which persisted at 5 weeks (P<0.01; P<0.05). In the ovine model of PCOS, OD causes a sustained reduction in ovarian stromal blood flow with an increased ovarian artery resistance index associated with atresia of antral follicles.
authors.affiliation: Medical Research Council Centre for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Fiona
authors.initials: F
authors.lastname: Connolly
authors.affiliation: School of Health, Life and Social Sciences, Edinburgh Napier University, Edinburgh, United Kingdom.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Rae
authors.affiliation: Institute of Biophysics, Biochemistry and Bio-Engineering, Heriot Watt University, Edinburgh, United Kingdom.
authors.forename: Mairead
authors.initials: M
authors.lastname: Butler
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Klibanov
authors.affiliation: Institute of Biophysics, Biochemistry and Bio-Engineering, Heriot Watt University, Edinburgh, United Kingdom.
authors.forename: Vassilis
authors.initials: V
authors.lastname: Sboros
authors.affiliation: Medical Research Council Centre for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Alan S
authors.initials: AS
authors.lastname: McNeilly
authors.affiliation: Medical Research Council Centre for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: W Colin
authors.initials: WC
authors.lastname: Duncan
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003972:Diathermy; D004195:Disease Models, Animal; D005260:Female; D056726:Genetic Association Studies; D007249:Inflammation / Q000473:pathology; D045423:Microbubbles; D006080:Ovarian Follicle / Q000473:pathology; D010053:Ovary / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D011247:Pregnancy; D011374:Progesterone / Q000097:blood; D060888:Real-Time Polymerase Chain Reaction; D034561:Sheep, Domestic; D018608:Ultrasonography, Doppler
chemical_list: D015415:Biomarkers; D011374:Progesterone