Differential expression of endometrial integrins and progesterone receptor during the window of implantation in normo-ovulatory women treated with clomiphene citrate.
OBJECTIVE
To assess the effect of clomiphene citrate (CC) on endometrial epithelial integrins and P receptors (PR) during the window of implantation.


METHODS
Controlled, prospective, clinical study.


METHODS
Teaching hospital and university research laboratory.


METHODS
Thirty-one fertile, normo-ovulatory women participated in this trial. Thirteen women exhibited a CC-stimulated cycle with 50 mg on days 5-9, and 18 women with spontaneous menstrual cycles served as controls.


METHODS
Endometrial biopsies in the midluteal phase.


METHODS
Immunohistochemical determination and endometrial cellular localization of alpha1, alpha v, beta3, and alpha4 epithelial integrins and PR during the window of implantation. The staining intensity was assessed by a semiquantitative index (HSCORE) and compared by nonparametric Mann-Whitney test.


RESULTS
Higher plasma levels of P and E2 and delayed histologic dating of the endometrium (38%) were features of CC-treated women. In addition, a low epithelial beta3 integrin expression and persistent PR were observed in glandular epithelial cells of "out-of-phase" endometrial biopsies from CC-treated women. In contrast, in "in-phase" biopsies, neither epithelial PR nor beta3 integrin were different from spontaneous control cycles. There was no difference in the expression of alpha1, alpha v, and alpha4 between the groups studied.


CONCLUSIONS
The administration of clomiphene produces aberrant endometrial beta3 integrin expression in conjunction with a failure in the down-regulation of PR during the window of implantation in a significant number of normo-ovulatory women, notwithstanding the higher plasma P levels. Therefore, CC might affect the expression of endometrial receptivity markers.
Palomino
W Alberto
WA
Institute for Maternal and Child Research, School of Medicine, University of Chile, Santiago, Chile. palomino@email.unc.edu
Fuentes
Ariel
A
González
Rubén René
RR
Gabler
Fernando
F
Boric
Maria Angélica
MA
Vega
Margarita
M
Devoto
Luigi
L
D000328:Adult; D002996:Clomiphene / Q000008:administration & dosage*; D010064:Embryo Implantation / Q000187:drug effects* / Q000502:physiology; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000097:blood; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage*; D006801:Humans; D007150:Immunohistochemistry; D039661:Integrin beta3 / Q000378:metabolism*; D010060:Ovulation / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D011374:Progesterone / Q000097:blood; D011446:Prospective Studies; D011980:Receptors, Progesterone / Q000378:metabolism*
D005300:Fertility Agents, Female; D039661:Integrin beta3; D011980:Receptors, Progesterone; D002996:Clomiphene; D011374:Progesterone; D004958:Estradiol