title: A critical period of progesterone withdrawal precedes endometrial breakdown and shedding in mouse menstrual-like model.
abstract: OBJECTIVE
  Is there a critical period of progesterone (P4) withdrawal in a mouse menstrual-like model, and at what time after P4 withdrawal endometrial breakdown become irreversible?
  
  
  CONCLUSIONS
  Our results showed that a 12-16 h critical period of P4 withdrawal exists in the mouse menstrual-like model.
  
  
  BACKGROUND
  P4 withdrawal is the trigger for endometrial breakdown and shedding during menstruation. To date, the molecular mechanisms responsible for endometrial breakdown have not been fully elucidated. In an ovariectomized macaque model, P4 replacement could reduce or block menses during a period of 36-48 h after P4 withdrawal, but after this, P4 supplementation did not reduce or block menses. Thus, in the macaque, a critical period of P4 withdrawal lasting 36-48 h exists before menses.
  
  
  METHODS
  We created a mouse menstrual-like model and restored P4 at four time points. The total number of mice was 120 and the duration of treatment was 26 days.
  
  
  METHODS
  A mouse menstrual model was characterized by endometrial morphology and plasma P4 levels. P4 was then replaced at 8, 12, 16 and 20 h after the removal of P4 implants. Vaginal smears, endometrial morphology, plasma P4 levels and expression patterns of matrix metalloproteinases (MMP-2, MMP-3, MMP-9, MMP-10, MMP-11 and MMP-13) were investigated.
  
  
  RESULTS
  Replacement of P4 at 8 and 12 h blocked menstrual-like bleeding and endometrial shedding; however, replacement at 16 and 20 h did not suppress bleeding or shedding. Furthermore, P4 replacement at 12 h inhibited the expression of all latent or active MMPs; however, replacement at 16 h inhibited only pMMP-13.
  
  
  CONCLUSIONS
  Although determination of the critical period in vivo using a mouse model was successfully demonstrated, the mechanisms of P4 regulation need to be further explored.
  
  
  CONCLUSIONS
  The experimental opportunities provided by the mouse model will facilitate understanding the role of P4 in the regulation of menstruation and help to identify new targets for the clinical intervention of menstrual disorders.
authors.affiliation: Graduate School, Peking Union Medical College, 100730 Beijing, People's Republic of China.
authors.forename: Qianxing
authors.initials: Q
authors.lastname: Wang
authors.forename: Xiangbo
authors.initials: X
authors.lastname: Xu
authors.forename: Bin
authors.initials: B
authors.lastname: He
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Li
authors.forename: Xihua
authors.initials: X
authors.lastname: Chen
authors.forename: Jiedong
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D030762:Estrous Cycle / Q000097:blood / Q000502:physiology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D011374:Progesterone / Q000097:blood*; D013997:Time Factors; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects
chemical_list: D011374:Progesterone
keywords: critical period; matrix metalloproteinase; mouse menstrual-like model; progesterone replacement; progesterone withdrawal