Identification of sites of STAT3 action in the female reproductive tract through conditional gene deletion

Rebecca L. Robker, Laura N. Watson, Sarah A. Robertson, Kylie R. Dunning, Eileen A. McLaughlin, Darryl L. Russell

Research output: Contribution to journalArticle

14 Citations (Scopus)
2 Downloads (Pure)

Abstract

The STAT3 transcription factor is a pleiotropic transducer of signalling by hormones, growth factors and cytokines that has been identified in the female reproductive tract from oocytes and granulosa cells of the ovary to uterine epithelial and stromal cells. In the present study we used transgenic models to investigate the importance of STAT3 for reproductive performance in these different tissues. The Cre-LoxP system was used to delete STAT3 in oocytes by crossing Stat3 fl/fl with Zp3-cre+ mice, or in ovarian granulosa cells and uterine stroma by crossing with Amhr2-Cre+ mice. Surprisingly, deletion of STAT3 in oocytes had no effect on fertility indicating that the abundance of STAT3 protein in maturing oocytes and fertilized zygotes is not essential to these developmental stages. In Stat3fl/fl;Amhr2-cre + females impaired fertility was observed through significantly fewer litters and smaller litter size. Ovulation rate, oocyte fertilization and development to blastocyst were unaffected in this line; however, poor recombination efficiency in granulosa cells had yielded no net change in STAT3 protein abundance. In contrast, uteri from these mice showed STAT3 protein depletion selectively from the stomal compartment. A significant reduction in number of viable fetuses on gestational day 18, increased fetal resorptions and disrupted placental morphology were evident causes of the reduced fertility. In conclusion, this study defines an important role for STAT3 in uterine stromal cells during embryo implantation and the development of a functional placenta.

Original languageEnglish
Article numbere101182
Pages (from-to)1-10
Number of pages10
JournalPLoS One
Volume9
Issue number7
DOIs
Publication statusPublished - 1 Jul 2014
Externally publishedYes

Fingerprint

STAT3 Transcription Factor
gene deletion
Gene Deletion
Oocytes
oocytes
Genes
Granulosa Cells
granulosa cells
Fertility
stromal cells
Stromal Cells
mice
fetal resorption
Fetal Resorption
Hormones
embryo implantation
Litter Size
female fertility
protein depletion
Zygote

Cite this

Robker, R. L., Watson, L. N., Robertson, S. A., Dunning, K. R., McLaughlin, E. A., & Russell, D. L. (2014). Identification of sites of STAT3 action in the female reproductive tract through conditional gene deletion. PLoS One, 9(7), 1-10. [e101182]. https://doi.org/10.1371/journal.pone.0101182
Robker, Rebecca L. ; Watson, Laura N. ; Robertson, Sarah A. ; Dunning, Kylie R. ; McLaughlin, Eileen A. ; Russell, Darryl L. / Identification of sites of STAT3 action in the female reproductive tract through conditional gene deletion. In: PLoS One. 2014 ; Vol. 9, No. 7. pp. 1-10.
@article{5661185612814eae888ab14840608dcc,
title = "Identification of sites of STAT3 action in the female reproductive tract through conditional gene deletion",
abstract = "The STAT3 transcription factor is a pleiotropic transducer of signalling by hormones, growth factors and cytokines that has been identified in the female reproductive tract from oocytes and granulosa cells of the ovary to uterine epithelial and stromal cells. In the present study we used transgenic models to investigate the importance of STAT3 for reproductive performance in these different tissues. The Cre-LoxP system was used to delete STAT3 in oocytes by crossing Stat3 fl/fl with Zp3-cre+ mice, or in ovarian granulosa cells and uterine stroma by crossing with Amhr2-Cre+ mice. Surprisingly, deletion of STAT3 in oocytes had no effect on fertility indicating that the abundance of STAT3 protein in maturing oocytes and fertilized zygotes is not essential to these developmental stages. In Stat3fl/fl;Amhr2-cre + females impaired fertility was observed through significantly fewer litters and smaller litter size. Ovulation rate, oocyte fertilization and development to blastocyst were unaffected in this line; however, poor recombination efficiency in granulosa cells had yielded no net change in STAT3 protein abundance. In contrast, uteri from these mice showed STAT3 protein depletion selectively from the stomal compartment. A significant reduction in number of viable fetuses on gestational day 18, increased fetal resorptions and disrupted placental morphology were evident causes of the reduced fertility. In conclusion, this study defines an important role for STAT3 in uterine stromal cells during embryo implantation and the development of a functional placenta.",
keywords = "Animals, Female, Gene Deletion, Genitalia, Female/physiology, Infertility, Female/genetics, Male, Mice, STAT3 Transcription Factor/genetics",
author = "Robker, {Rebecca L.} and Watson, {Laura N.} and Robertson, {Sarah A.} and Dunning, {Kylie R.} and McLaughlin, {Eileen A.} and Russell, {Darryl L.}",
year = "2014",
month = "7",
day = "1",
doi = "10.1371/journal.pone.0101182",
language = "English",
volume = "9",
pages = "1--10",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "7",

}

Robker, RL, Watson, LN, Robertson, SA, Dunning, KR, McLaughlin, EA & Russell, DL 2014, 'Identification of sites of STAT3 action in the female reproductive tract through conditional gene deletion', PLoS One, vol. 9, no. 7, e101182, pp. 1-10. https://doi.org/10.1371/journal.pone.0101182

Identification of sites of STAT3 action in the female reproductive tract through conditional gene deletion. / Robker, Rebecca L.; Watson, Laura N.; Robertson, Sarah A.; Dunning, Kylie R.; McLaughlin, Eileen A.; Russell, Darryl L.

In: PLoS One, Vol. 9, No. 7, e101182, 01.07.2014, p. 1-10.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Identification of sites of STAT3 action in the female reproductive tract through conditional gene deletion

AU - Robker, Rebecca L.

AU - Watson, Laura N.

AU - Robertson, Sarah A.

AU - Dunning, Kylie R.

AU - McLaughlin, Eileen A.

AU - Russell, Darryl L.

PY - 2014/7/1

Y1 - 2014/7/1

N2 - The STAT3 transcription factor is a pleiotropic transducer of signalling by hormones, growth factors and cytokines that has been identified in the female reproductive tract from oocytes and granulosa cells of the ovary to uterine epithelial and stromal cells. In the present study we used transgenic models to investigate the importance of STAT3 for reproductive performance in these different tissues. The Cre-LoxP system was used to delete STAT3 in oocytes by crossing Stat3 fl/fl with Zp3-cre+ mice, or in ovarian granulosa cells and uterine stroma by crossing with Amhr2-Cre+ mice. Surprisingly, deletion of STAT3 in oocytes had no effect on fertility indicating that the abundance of STAT3 protein in maturing oocytes and fertilized zygotes is not essential to these developmental stages. In Stat3fl/fl;Amhr2-cre + females impaired fertility was observed through significantly fewer litters and smaller litter size. Ovulation rate, oocyte fertilization and development to blastocyst were unaffected in this line; however, poor recombination efficiency in granulosa cells had yielded no net change in STAT3 protein abundance. In contrast, uteri from these mice showed STAT3 protein depletion selectively from the stomal compartment. A significant reduction in number of viable fetuses on gestational day 18, increased fetal resorptions and disrupted placental morphology were evident causes of the reduced fertility. In conclusion, this study defines an important role for STAT3 in uterine stromal cells during embryo implantation and the development of a functional placenta.

AB - The STAT3 transcription factor is a pleiotropic transducer of signalling by hormones, growth factors and cytokines that has been identified in the female reproductive tract from oocytes and granulosa cells of the ovary to uterine epithelial and stromal cells. In the present study we used transgenic models to investigate the importance of STAT3 for reproductive performance in these different tissues. The Cre-LoxP system was used to delete STAT3 in oocytes by crossing Stat3 fl/fl with Zp3-cre+ mice, or in ovarian granulosa cells and uterine stroma by crossing with Amhr2-Cre+ mice. Surprisingly, deletion of STAT3 in oocytes had no effect on fertility indicating that the abundance of STAT3 protein in maturing oocytes and fertilized zygotes is not essential to these developmental stages. In Stat3fl/fl;Amhr2-cre + females impaired fertility was observed through significantly fewer litters and smaller litter size. Ovulation rate, oocyte fertilization and development to blastocyst were unaffected in this line; however, poor recombination efficiency in granulosa cells had yielded no net change in STAT3 protein abundance. In contrast, uteri from these mice showed STAT3 protein depletion selectively from the stomal compartment. A significant reduction in number of viable fetuses on gestational day 18, increased fetal resorptions and disrupted placental morphology were evident causes of the reduced fertility. In conclusion, this study defines an important role for STAT3 in uterine stromal cells during embryo implantation and the development of a functional placenta.

KW - Animals

KW - Female

KW - Gene Deletion

KW - Genitalia, Female/physiology

KW - Infertility, Female/genetics

KW - Male

KW - Mice

KW - STAT3 Transcription Factor/genetics

UR - http://www.scopus.com/inward/record.url?scp=84903727317&partnerID=8YFLogxK

UR - http://www.mendeley.com/research/identification-sites-stat3-action-female-reproductive-tract-through-conditional-gene-deletion-1

U2 - 10.1371/journal.pone.0101182

DO - 10.1371/journal.pone.0101182

M3 - Article

VL - 9

SP - 1

EP - 10

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 7

M1 - e101182

ER -

Robker RL, Watson LN, Robertson SA, Dunning KR, McLaughlin EA, Russell DL. Identification of sites of STAT3 action in the female reproductive tract through conditional gene deletion. PLoS One. 2014 Jul 1;9(7):1-10. e101182. https://doi.org/10.1371/journal.pone.0101182