title: Changes in vaginal physiology of menopausal women with type 2 diabetes.
abstract: BACKGROUND
  Metabolic disorders, such as type 2 diabetes, have been associated with an increased risk of development of female sexual dysfunction (FSD). In experimental studies, vascular, neuronal, and hormonal responsiveness alteration at vaginal level were proposed as contributors to the onset of FSD in women with diabetes; however, conclusive data on humans are still lacking.
  
  
  OBJECTIVE
  The study aimed to assess changes in vascularization, sex steroid receptors, nitric oxide synthase, and aquaporin-2 (AQP2) expression occurring at vaginal level in women with diabetes.
  
  
  METHODS
  Vaginal biopsies were obtained from 21 postmenopausal women, 10 of whom were diagnosed as having type 2 diabetes mellitus. CD31, estrogen receptor-α (ERα) and androgen receptor (AR) expression and localization were analyzed by immunostaining. Expression of endothelial (eNOS) and neuronal (nNOS) nitric oxide synthase isoforms and AQP2 were also assessed in vaginal samples.
  
  
  METHODS
  Changes in vaginal vascularization, sex steroids receptor, eNOS, nNOS and AQP2 expression.
  
  
  RESULTS
  Vaginal samples from women with diabetes showed an increased microvessel density in the lamina propria, which were morphologically disrupted suggesting an angiogenic compensatory mechanism. While no differences were seen in ERα, AR expression was significantly reduced in the vaginal epithelium and lamina propria of women with diabetes. Similarly, the gene and protein expressions of both nNOS and eNOS were significantly reduced in patients with diabetes, while AQP2 mRNAs level did not significantly differ between the two groups.
  
  
  CONCLUSIONS
  Diabetes greatly impacts vaginal physiology, being associated with alterations of the vaginal lamina propria vascular network, nitrergic signaling, and AR expression. These alterations may contribute to the increased risk of FSD development in women with diabetes.
authors.affiliation: Center for Applied Biomedical Research (CRBA), Department of Surgical and Medical Sciences, University of Bologna and S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Baldassarre
authors.affiliation: Gynecology and Physiopathology of Human Reproduction, University of Bologna and S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Alvisi
authors.affiliation: Gynecology and Physiopathology of Human Reproduction, University of Bologna and S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Berra
authors.affiliation: Gynecology and Physiopathology of Human Reproduction, University of Bologna and S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Martelli
authors.affiliation: Gynecology and Physiopathology of Human Reproduction, University of Bologna and S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Farina
authors.affiliation: Department of Pathology, Rizzoli Orthopedics Institute, Bologna, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Righi
authors.affiliation: Center for Applied Biomedical Research (CRBA), Department of Surgical and Medical Sciences, University of Bologna and S. Orsola-Malpighi Hospital, Bologna, Italy.|Gynecology and Physiopathology of Human Reproduction, University of Bologna and S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Meriggiola
mesh_terms: D000728:Androgens / Q000378:metabolism; D051399:Aquaporin 2; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D047628:Estrogen Receptor alpha; D005260:Female; D006801:Humans; D008593:Menopause / Q000502:physiology*; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D011944:Receptors, Androgen / Q000235:genetics; D012735:Sexual Dysfunction, Physiological / Q000209:etiology / Q000503:physiopathology*; D014621:Vagina / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D000728:Androgens; D051399:Aquaporin 2; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D011944:Receptors, Androgen; C496320:NOS1 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I
keywords: Aquaporin-2; Female Sexual Dysfunction (FSD); Nitric Oxide Synthase; Sex Steroids Receptors; Type 2 Diabetes; Vagina; Vaginal Vascularization