title: Effects of GnRHa on early embryonic development in mice receiving cyclophosphamide.
abstract: OBJECTIVE
  There is a controversy whether GnRH agonist can reduce the deleterious effects of chemotherapy to prevent ovarian failure. We aimed to examine the possible protective effects of a gonadotrophin-releasing hormone agonist (GnRHa) on the fertilization rate and sequential embryonic development in mouse oocytes exposed to Cy.
  
  
  METHODS
  Mice were assigned to three groups of six animals each. A single dose of 75 mg/kg Cy was given intraperitoneally to the Cy mice group. The subcutaneous GnRHa injection was initiated 1 week before and continued for 1 week after the Cy injection in the GnRHa + Cy group. The animals given cyclophosphamide mated 1 week after the Cy injection. At the end of the injection period, the animals underwent a superovulation regime with pregnant mare serum gonadotrophin and human chorionic gonadotrophin and were mated. Early embryos were collected at 48 h after mating. The control group received only the superovulation regime and then mated.
  
  
  RESULTS
  Cyclophosphamide caused a significant decrease in the fertilization rate (p < 0.001), whereas the GnRHa improved the rate when compared to control group. The GnRHa induced a marked increase in the rate for 2-cell embryos compared with the Cy group (p = 0.003). In both Cy-injected groups, the rates for the 4-cell embryos were lower than those of the control animals (p < 0.001). However, this rate was higher in the GnRHa + Cy group than in the only Cy group. Morphologically abnormal embryos showed such characteristics as condensed cytoplasm, milky cytoplasm, fragmentation, and an empty zona pellucida.
  
  
  CONCLUSIONS
  These results demonstrated that the GnRHa preserved the oocyte capability to develop into an embryo against ovarian toxic chemotherapy. Thus, we suggest that GnRHa cotreatment could increase the number and quality of early embryos in mice.
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kanter
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, Trakya University, 22030, Edirne, Turkey. melikesapmaz@yahoo.com.
authors.forename: Melike
authors.initials: M
authors.lastname: Sapmaz-Metin
authors.affiliation: Department of Thoracic Surgery, Sarikamis State Hospital, Kars, Turkey.
authors.forename: Bilkay
authors.initials: B
authors.lastname: Serez
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000494:pharmacology*; D006063:Chorionic Gonadotropin / Q000097:blood; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology*; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D005306:Fertilization / Q000187:drug effects*; D005307:Fertilization in Vitro / Q000379:methods; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006736:Horses; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D009865:Oocytes / Q000187:drug effects*; D010049:Ovarian Diseases / Q000139:chemically induced / Q000517:prevention & control; D011247:Pregnancy; D020011:Protective Agents / Q000627:therapeutic use
chemical_list: D018906:Antineoplastic Agents, Alkylating; D006063:Chorionic Gonadotropin; D020011:Protective Agents; D007987:Gonadotropin-Releasing Hormone; D003520:Cyclophosphamide
keywords: Cyclophosphamide; GnRH agonist; Mouse; Preimplantation embryo