LPA3-mediated lysophosphatidic acid signalling in embryo implantation and spacing.
Every successful pregnancy requires proper embryo implantation. Low implantation rate is a major problem during infertility treatments using assisted reproductive technologies. Here we report a newly discovered molecular influence on implantation through the lysophosphatidic acid (LPA) receptor LPA3 (refs 2-4). Targeted deletion of LPA3 in mice resulted in significantly reduced litter size, which could be attributed to delayed implantation and altered embryo spacing. These two events led to delayed embryonic development, hypertrophic placentas shared by multiple embryos and embryonic death. An enzyme demonstrated to influence implantation, cyclooxygenase 2 (COX2) (ref. 5), was downregulated in LPA3-deficient uteri during pre-implantation. Downregulation of COX2 led to reduced levels of prostaglandins E2 and I2 (PGE2 and PGI2), which are critical for implantation. Exogenous administration of PGE2 or carbaprostacyclin (a stable analogue of PGI2) into LPA3-deficient female mice rescued delayed implantation but did not rescue defects in embryo spacing. These data identify LPA3 receptor-mediated signalling as having an influence on implantation, and further indicate linkage between LPA signalling and prostaglandin biosynthesis.
Ye
Xiaoqin
X
Department of Molecular Biology, Helen L. Dorris Child and Adolescent Neuropsychiatric Disorder Institute, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Hama
Kotaro
K
Contos
James J A
JJ
Anliker
Brigitte
B
Inoue
Asuka
A
Skinner
Michael K
MK
Suzuki
Hiroshi
H
Amano
Tomokazu
T
Kennedy
Grace
G
Arai
Hiroyuki
H
Aoki
Junken
J
Chun
Jerold
J
D000818:Animals; D051546:Cyclooxygenase 2; D010064:Embryo Implantation / Q000187:drug effects / Q000502:physiology*; D020964:Embryo Loss; D004622:Embryo, Mammalian / Q000196:embryology* / Q000378:metabolism*; D005260:Female; D008246:Lysophospholipids / Q000378:metabolism*; D051379:Mice; D010920:Placenta / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D011453:Prostaglandins / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014599:Uterus / Q000378:metabolism
D008246:Lysophospholipids; D011453:Prostaglandins; D012333:RNA, Messenger; D049368:Receptors, Lysophosphatidic Acid; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C032881:lysophosphatidic acid