title: Differential expression of functionality markers in mid-secretory endometrium of infertile women under treatment with ovulation-inducing agents.
abstract: OBJECTIVE
  To analyze the expression of protein markers related to cell proliferation and death, as well as oestrogen and progesterone receptors in the endometrium of infertile women with hypothalamic-pituitary dysfunction treated with clomiphene citrate (CC) or recombinant follicle-stimulating hormone (rFSH), and compare them with ovulatory women.
  
  
  METHODS
  The study included 12 control ovulatory women and 29 anovulatory women, 19 of whom underwent ovulation induction with CC (n = 12) or rFSH (n = 5). Endometrial biopsies were obtained by Pipelle during the mid-secretory phase. Samples were stained with haematoxylin and eosin. Immunohistochemistry of proteins related to cell proliferation and cell death, as well as steroid receptors, was undertaken, and apoptosis was determined using TUNEL analysis.
  
  
  RESULTS
  Immunohistochemical analysis of Ki67 expression showed significantly higher expression in the glandular epithelium of ovulatory women compared with the other groups. Glandular oestrogen receptor α expression was significantly lower in rFSH-treated women compared with ovulatory women. The number of apoptotic cells, Bax expression and progesterone receptor expression were similar in all groups. In contrast, Bcl-2 expression was significantly lower in the glandular epithelium of rFSH-treated women.
  
  
  CONCLUSIONS
  In infertile women with hypothalamic-pituitary dysfunction, treatment with ovulation-inducing agents modifies the expression of proteins involved in cell proliferation and death, as well as the expression of steroid hormone receptors in the endometrium. These differences may help to explain, at the molecular level, the functionality of the endometrium during the implantation window, and may help to optimize pregnancy rates obtained with these treatments.
authors.affiliation: Facultad de Química, Universidad Nacional Autónoma de México, DF, Mexico.
authors.forename: F J
authors.initials: FJ
authors.lastname: Valdez-Morales
authors.forename: A
authors.initials: A
authors.lastname: Gamboa-Domínguez
authors.forename: V S
authors.initials: VS
authors.lastname: Vital-Reyes
authors.forename: J C
authors.initials: JC
authors.lastname: Hinojosa-Cruz
authors.forename: C A
authors.initials: CA
authors.lastname: Mendoza-Rodríguez
authors.forename: A
authors.initials: A
authors.lastname: García-Carrancá
authors.forename: M
authors.initials: M
authors.lastname: Cerbón
mesh_terms: D000328:Adult; D016923:Cell Death / Q000502:physiology; D049109:Cell Proliferation; D002996:Clomiphene / Q000627:therapeutic use*; D004717:Endometrium / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000096:biosynthesis; D005260:Female; D005300:Fertility Agents, Female / Q000627:therapeutic use*; D005640:Follicle Stimulating Hormone / Q000627:therapeutic use*; D006801:Humans; D007247:Infertility, Female / Q000188:drug therapy / Q000378:metabolism*; D008183:Luteal Phase / Q000502:physiology; D010062:Ovulation Induction; D011980:Receptors, Progesterone / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D005300:Fertility Agents, Female; D011980:Receptors, Progesterone; D051028:bcl-2-Associated X Protein; D002996:Clomiphene; D005640:Follicle Stimulating Hormone
keywords: Clomiphene citrate; Human endometrium; Infertility; Ovulation induction; Recombinant follicle-stimulating hormone