Effect of single post-ovulatory administration of mifepristone (RU486) on transcript profile during the receptive period in human endometrium

Catherina A. Cuevas, Alejandro Tapia-Pizarro, Ana María Salvatierra, David J. Munroe, Luis Velasquez, Horacio B. Croxatto

Resultado de la investigación: Article

  • 4 Citas

Resumen

Progesterone regulates uterine function during the luteal phase and is essential for the acquisition of endometrial receptivity. The objective of the present study was to identify endometrial transcripts whose expression is altered during the window of implantation after the administration of 200 mg of the antiprogestin mifepristone, 48 h after the LH peak (LH+2, LH+0=LH peak), and to determine the relationship of these transcripts with those regulated during the acquisition of receptivity. Endometrial samples were obtained in LH+7 from seven women of proven fertility, each one contributing with one cycle treated with placebo and another with mifepristone. Additionally, endometrial samples were obtained in LH+2 and LH+7 during a single untreated spontaneous cycle from seven normal fertile women as a reference. DNA microarrays were used to identify transcripts significantly regulated (defined as ≥2.0-fold change with false discovery rate below 1% using t-test) with the administration of mifepristone vs placebo, or during the transition from pre-receptive to receptive (LH+2 vs LH+7). Approximately 2000 transcripts were significantly regulated in both comparisons (mifepristone vs placebo and LH+2 vs LH+7), but only 777 of them were coincident and displayed opposite regulation except for 25. The mRNA level for eight selected genes regulated by mifepristone was confirmed by real-time RT-PCR. We conclude that not all changes in endometrial transcript levels occurring in the transition from LH+2 to LH+7 seem to be regulated by the progesterone receptor and ∼37% of the genes whose transcript levels changed by effect of mifepristone could be associated with the acquisition of receptivity.

IdiomaEnglish
Páginas331-349
Número de páginas19
PublicaciónReproduction
Volumen151
Número de edición4
DOI
EstadoPublished - 1 abr 2016

Huella dactilar

Mifepristone
Endometrium
Placebos
Luteal Phase
Progesterone Receptors
Oligonucleotide Array Sequence Analysis
Genes
Progesterone
Fertility
Real-Time Polymerase Chain Reaction
Messenger RNA

ASJC Scopus subject areas

  • Embryology
  • Reproductive Medicine
  • Endocrinology
  • Obstetrics and Gynaecology
  • Cell Biology

Citar esto

Cuevas, Catherina A. ; Tapia-Pizarro, Alejandro ; Salvatierra, Ana María ; Munroe, David J. ; Velasquez, Luis ; Croxatto, Horacio B. / Effect of single post-ovulatory administration of mifepristone (RU486) on transcript profile during the receptive period in human endometrium. En: Reproduction. 2016 ; Vol. 151, N.º 4. pp. 331-349.
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title = "Effect of single post-ovulatory administration of mifepristone (RU486) on transcript profile during the receptive period in human endometrium",
abstract = "Progesterone regulates uterine function during the luteal phase and is essential for the acquisition of endometrial receptivity. The objective of the present study was to identify endometrial transcripts whose expression is altered during the window of implantation after the administration of 200 mg of the antiprogestin mifepristone, 48 h after the LH peak (LH+2, LH+0=LH peak), and to determine the relationship of these transcripts with those regulated during the acquisition of receptivity. Endometrial samples were obtained in LH+7 from seven women of proven fertility, each one contributing with one cycle treated with placebo and another with mifepristone. Additionally, endometrial samples were obtained in LH+2 and LH+7 during a single untreated spontaneous cycle from seven normal fertile women as a reference. DNA microarrays were used to identify transcripts significantly regulated (defined as ≥2.0-fold change with false discovery rate below 1{\%} using t-test) with the administration of mifepristone vs placebo, or during the transition from pre-receptive to receptive (LH+2 vs LH+7). Approximately 2000 transcripts were significantly regulated in both comparisons (mifepristone vs placebo and LH+2 vs LH+7), but only 777 of them were coincident and displayed opposite regulation except for 25. The mRNA level for eight selected genes regulated by mifepristone was confirmed by real-time RT-PCR. We conclude that not all changes in endometrial transcript levels occurring in the transition from LH+2 to LH+7 seem to be regulated by the progesterone receptor and ∼37{\%} of the genes whose transcript levels changed by effect of mifepristone could be associated with the acquisition of receptivity.",
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Effect of single post-ovulatory administration of mifepristone (RU486) on transcript profile during the receptive period in human endometrium. / Cuevas, Catherina A.; Tapia-Pizarro, Alejandro; Salvatierra, Ana María; Munroe, David J.; Velasquez, Luis; Croxatto, Horacio B.

En: Reproduction, Vol. 151, N.º 4, 01.04.2016, p. 331-349.

Resultado de la investigación: Article

TY - JOUR

T1 - Effect of single post-ovulatory administration of mifepristone (RU486) on transcript profile during the receptive period in human endometrium

AU - Cuevas, Catherina A.

AU - Tapia-Pizarro, Alejandro

AU - Salvatierra, Ana María

AU - Munroe, David J.

AU - Velasquez, Luis

AU - Croxatto, Horacio B.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Progesterone regulates uterine function during the luteal phase and is essential for the acquisition of endometrial receptivity. The objective of the present study was to identify endometrial transcripts whose expression is altered during the window of implantation after the administration of 200 mg of the antiprogestin mifepristone, 48 h after the LH peak (LH+2, LH+0=LH peak), and to determine the relationship of these transcripts with those regulated during the acquisition of receptivity. Endometrial samples were obtained in LH+7 from seven women of proven fertility, each one contributing with one cycle treated with placebo and another with mifepristone. Additionally, endometrial samples were obtained in LH+2 and LH+7 during a single untreated spontaneous cycle from seven normal fertile women as a reference. DNA microarrays were used to identify transcripts significantly regulated (defined as ≥2.0-fold change with false discovery rate below 1% using t-test) with the administration of mifepristone vs placebo, or during the transition from pre-receptive to receptive (LH+2 vs LH+7). Approximately 2000 transcripts were significantly regulated in both comparisons (mifepristone vs placebo and LH+2 vs LH+7), but only 777 of them were coincident and displayed opposite regulation except for 25. The mRNA level for eight selected genes regulated by mifepristone was confirmed by real-time RT-PCR. We conclude that not all changes in endometrial transcript levels occurring in the transition from LH+2 to LH+7 seem to be regulated by the progesterone receptor and ∼37% of the genes whose transcript levels changed by effect of mifepristone could be associated with the acquisition of receptivity.

AB - Progesterone regulates uterine function during the luteal phase and is essential for the acquisition of endometrial receptivity. The objective of the present study was to identify endometrial transcripts whose expression is altered during the window of implantation after the administration of 200 mg of the antiprogestin mifepristone, 48 h after the LH peak (LH+2, LH+0=LH peak), and to determine the relationship of these transcripts with those regulated during the acquisition of receptivity. Endometrial samples were obtained in LH+7 from seven women of proven fertility, each one contributing with one cycle treated with placebo and another with mifepristone. Additionally, endometrial samples were obtained in LH+2 and LH+7 during a single untreated spontaneous cycle from seven normal fertile women as a reference. DNA microarrays were used to identify transcripts significantly regulated (defined as ≥2.0-fold change with false discovery rate below 1% using t-test) with the administration of mifepristone vs placebo, or during the transition from pre-receptive to receptive (LH+2 vs LH+7). Approximately 2000 transcripts were significantly regulated in both comparisons (mifepristone vs placebo and LH+2 vs LH+7), but only 777 of them were coincident and displayed opposite regulation except for 25. The mRNA level for eight selected genes regulated by mifepristone was confirmed by real-time RT-PCR. We conclude that not all changes in endometrial transcript levels occurring in the transition from LH+2 to LH+7 seem to be regulated by the progesterone receptor and ∼37% of the genes whose transcript levels changed by effect of mifepristone could be associated with the acquisition of receptivity.

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U2 - 10.1530/REP-15-0458

DO - 10.1530/REP-15-0458

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JO - Reproduction

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SN - 1470-1626

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ER -