title: Effect of oral administration of low-dose follicle stimulating hormone on hyperandrogenized mice as a model of polycystic ovary syndrome.
abstract: BACKGROUND
  Polycystic Ovary Syndrome (PCOS) is a widespread reproductive disorder characterized by a disruption of follicular growth and anovulatory infertility. In women with PCOS, follicular growth and ovulation can be induced by subcutaneous injections of low doses of follicle stimulating hormone (FSH). The aim of this study was to determine the effect of oral administration of recombinant human FSH (rhFSH) on follicle development in a PCOS murine model. Moreover, since it is unlikely that intact rhFSH is present into the circulation after oral administration, the biological activity of a peptide fragment, derived from the predicted enzymatic cleavage sites with the FSH molecule, was investigated in vitro on cumulus-enclosed oocytes (COCs).
  
  
  METHODS
  Female peripubertal mice were injected with dehydroepiandrosterone (DHEA) diluted in sesame oil for 20 consecutive days and orally treated with a saline solution of rhFSH. A control group received only sesame oil and saline solution. At the end of treatments, blood was analyzed for hormone concentrations and ovaries were processed for morphological analysis. The presumptive bioactive peptide was added during in vitro maturation of bovine COCs and the effects on cumulus expansion and on maturation rate were evaluated.
  
  
  RESULTS
  DHEA treatment increased serum levels of testosterone, estradiol and progesterone as well as the percentage of cystic follicles. Orally administered rhFSH restored estradiol level and reduced the percentage of cystic follicles. Despite these results indicating a reduction of the severity of PCOS in the mouse model, the presumptive bioactive peptide did not mimic the effect of rhFSH and failed to induce bovine cumulus expansion and oocyte maturation in vitro.
  
  
  CONCLUSIONS
  Although further studies are needed, the present data supports the concept that orally administrated FSH could attenuate some of the characteristic of PCOS in the mouse model.
authors.affiliation: Reproductive and Developmental Biology Laboratory, Department of Health, Animal Science and Food Safety, Università degli Studi di Milano, Via Celoria 10, Milan, 20133, Italy. irene.tessaro@unimi.it.
authors.forename: Irene
authors.initials: I
authors.lastname: Tessaro
authors.affiliation: Reproductive and Developmental Biology Laboratory, Department of Health, Animal Science and Food Safety, Università degli Studi di Milano, Via Celoria 10, Milan, 20133, Italy. silvia.modina@unimi.it.|Interdepartmental Research Centre for the Study of Biological Effects of Nano-concentrations (CREBION), Università degli Studi di Milano, Via Celoria 10, Milan, 20133, Italy. silvia.modina@unimi.it.
authors.forename: Silvia C
authors.initials: SC
authors.lastname: Modina
authors.affiliation: Reproductive and Developmental Biology Laboratory, Department of Health, Animal Science and Food Safety, Università degli Studi di Milano, Via Celoria 10, Milan, 20133, Italy. federica.franciosi1@unimi.it.
authors.forename: Federica
authors.initials: F
authors.lastname: Franciosi
authors.affiliation: Reproductive and Developmental Biology Laboratory, Department of Health, Animal Science and Food Safety, Università degli Studi di Milano, Via Celoria 10, Milan, 20133, Italy. giulsive@gmail.com.
authors.forename: Giulia
authors.initials: G
authors.lastname: Sivelli
authors.affiliation: Reproductive and Developmental Biology Laboratory, Department of Health, Animal Science and Food Safety, Università degli Studi di Milano, Via Celoria 10, Milan, 20133, Italy. laura.terzaghi@unimi.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Terzaghi
authors.affiliation: Reproductive and Developmental Biology Laboratory, Department of Health, Animal Science and Food Safety, Università degli Studi di Milano, Via Celoria 10, Milan, 20133, Italy. valentina.lodde@unimi.it.
authors.forename: Valentina
authors.initials: V
authors.lastname: Lodde
authors.affiliation: Reproductive and Developmental Biology Laboratory, Department of Health, Animal Science and Food Safety, Università degli Studi di Milano, Via Celoria 10, Milan, 20133, Italy. alberto.luciano@unimi.it.|Interdepartmental Research Centre for the Study of Biological Effects of Nano-concentrations (CREBION), Università degli Studi di Milano, Via Celoria 10, Milan, 20133, Italy. alberto.luciano@unimi.it.
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Luciano
mesh_terms: D000276:Adjuvants, Immunologic / Q000633:toxicity; D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D001141:Aromatase / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000633:toxicity; D004195:Disease Models, Animal; D004958:Estradiol / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D017588:Hyperandrogenism / Q000139:chemically induced / Q000188:drug therapy; D007271:Injections, Intradermal; D008807:Mice, Inbred BALB C; D009865:Oocytes / Q000187:drug effects; D006080:Ovarian Follicle / Q000187:drug effects; D010053:Ovary / Q000187:drug effects; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy*; D011994:Recombinant Proteins; D015430:Weight Gain
chemical_list: D000276:Adjuvants, Immunologic; D012739:Gonadal Steroid Hormones; D011994:Recombinant Proteins; D003687:Dehydroepiandrosterone; D004958:Estradiol; D005640:Follicle Stimulating Hormone; D001141:Aromatase