title: High FSH decreases the developmental potential of mouse oocytes and resulting fertilized embryos, but does not influence offspring physiology and behavior in vitro or in vivo.
abstract: OBJECTIVE
  Do different concentrations of FSH in the assisted reproductive technology (ART) procedure in vitro or in vivo affect the developmental competence of oocytes, the embryos and the offspring conceived from these embryos?
  
  
  CONCLUSIONS
  Improper FSH treatment (200 IU/l in vitro, 10 IU/ml in vivo and 200 IU/ml in vivo) impairs the development competence of oocyte and embryo, but does not influence offspring physiology and behavior.
  
  
  BACKGROUND
  Exogenous FSH has been widely used in the field of ART. However, the effects of different concentrations of FSH on the developmental competence of oocytes, embryos and the offspring conceived from these embryos, are still unknown.
  
  
  METHODS
  In a prospective study, a total of 45 mice at 8-10 weeks of age were primed in vivo with different dosages of FSH (9 mice in the 10 IU/ml, 10 mice in the 50 IU/ml, 10 mice in the 100 IU/ml and 16 mice in the 200 IU/ml groups). Fresh MII oocytes were retrieved from ovaries: this was designated as in vivo group. Thirty six mice at 8-10 weeks of age were sacrificed by cervical dislocation to obtain ovaries without FSH treatment (9 mice in the 0 IU/l, 9 mice in the 50 IU/l, 8 mice in the 100 IU/l and 10 mice in the 200 IU/l groups), and then the immature oocytes were collected from these ovaries and cultured in vitro matured medium supplemented with 0, 50, 100 and 200 IU/l FSH: this was designated as in vitro group.
  
  
  METHODS
  Spindle assembly of matured MII oocytes was stained via an immunofluorescence method and the oocytes ratio of normal spindle was analyzed. The developmental competence of the resulting fertilized embryos in the pre- and post-implantation stages was examined in in vitro and in vivo groups. Furthermore, physiological index, including reproductive potential and body weight, of the offspring was investigated by mating experiments and behavior index, including learning, memory, probing and intelligence, was tested by Morris water maze in in vitro and in vivo groups.
  
  
  RESULTS
  In the in vitro groups, the oocyte maturation competence, normal spindle assembly, blastocyst formation and implantation, as well as viable pup production were all impaired in the group treated with 200 IU/l FSH (P < 0.05). No differences were observed among the other three groups (P > 0.05). In the in vivo groups, 10 IU/ml FSH but not 200 IU/ml treatment influenced blastocyst formation and viable pup production (P < 0.05), although the high proportion of spindle assembly abnormality was only observed in the 200 IU/ml FSH treatment group (P < 0.05). Furthermore, there were no significant differences in terms of physiological index (reproductive potential and body weight) and behavior index (learning, memory, probing and intelligence) in offspring from in vitro and in vivo groups (P > 0.05).
  
  
  CONCLUSIONS
  The mouse model was used in this study. The results of the mouse follicle growth and oocyte development in responding to different concentrations of FSH are not 100% transferable to human, because of the physiological differences between mouse and human.
  
  
  CONCLUSIONS
  The findings indicated that FSH application in the field of ART is safe to the resulted offspring, but it should be more carefully used for each women in ART cycles because the inappropriate FSH concentration would decrease the oocyte developmental competence.
  
  
  BACKGROUND
  This work was partially supported by the Ministry of Science and Technology of China Grants (973 program; 2011CB944504), the Program for Changjiang Scholars and Innovative Research Team in University of Ministry of Education of China (30825038), the National Natural Science Funds for Young Scholar (31000661) and by the Joint Research Fund for Overseas, Hong Kong and Marco Scholars (31128013/C120205). None of the authors has any conflicts of interest.
authors: Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, No. 49 North HuaYuan Road, HaiDian District, Beijing 100191, China.
authors: Min
authors: M
authors: Li
authors: Yue
authors: Y
authors: Zhao
authors: Cui H
authors: CH
authors: Zhao
authors: Jie
authors: J
authors: Yan
authors: Ying L
authors: YL
authors: Yan
authors: Li
authors: L
authors: Rong
authors: Ping
authors: P
authors: Liu
authors: Huai-Liang
authors: HL
authors: Feng
authors: Yang
authors: Y
authors: Yu
authors: Jie
authors: J
authors: Qiao
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001755:Blastocyst / Q000166:cytology; D003470:Culture Media / Q000737:chemistry; D046149:Embryo Culture Techniques; D005260:Female; D005306:Fertilization / Q000502:physiology*; D005640:Follicle Stimulating Hormone / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007361:Intelligence Tests; D008297:Male; D008568:Memory; D051379:Mice; D008813:Mice, Inbred ICR; D008856:Microscopy, Fluorescence; D009865:Oocytes / Q000166:cytology / Q000502:physiology*; D006080:Ovarian Follicle / Q000502:physiology; D027724:Reproductive Techniques, Assisted; D020554:Sperm Injections, Intracytoplasmic; D013094:Spermatozoa / Q000378:metabolism / Q000473:pathology
chemical_list: D003470:Culture Media; D005640:Follicle Stimulating Hormone