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Failure of Parturition in Mice Lacking the Prostaglandin F Receptor
Abstract
Mice lacking the gene encoding the receptor for prostaglandin F 2α (FP) developed normally but were unable to deliver normal fetuses at term. Although these FP-deficient mice showed no abnormality in the estrous cycle, ovulation, fertilization, or implantation, they did not respond to exogenous oxytocin because of the lack of induction of oxytocin receptor (a proposed triggering event in parturition), and they did not show the normal decline of serum progesterone concentrations that precedes parturition. Ovariectomy at day 19 of pregnancy restored induction of the oxytocin receptor and permitted successful delivery in the FP-deficient mice. These results indicate that parturition is initiated when prostaglandin F 2α interacts with FP in ovarian luteal cells of the pregnant mice to induce luteolysis.
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“Multiple factors initiate parturition, including fetal cortisol, maternal drop in progesterone, oxytocin, prostaglandin F2α and other endocrine factors56–59.”
From Conditional loss of ERK1 and ERK2 results in abnormal placentation and delayed parturition in the mouse (2019) · cites this paper as [58]
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Endocrine and Paracrine Regulation of Birth at Term and Preterm*
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“Mice carrying null mutations for genes encoding the PGF2a receptor (296), cytosolic phospholipase A2, and prostaglandin synthase type 1 (PGHS-1) (297) have delayed labor onset although neonatal viability is diminished.”
BackgroundTwo pathways for prostaglandin F2α synthesis by the primate periovulatory follicle
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“While studies with PGF2a receptor knockout mice suggest that PGF2a is not required for ovulation (Sugimoto et al. 1997), subfertility in mice lacking expression of the PGE2 receptor EP2 focused attention on PGE2 as the key ovulatory PG (Hizaki et al. 1999).”
BackgroundKamoshita, E., Ikeda, Y., Fujita, M., Amano, H., Oikawa, A., Suzuki, T., Ogawa, Y., Yamashina, S., Azuma, S., Narumiya, S., et al. (2006) · American Journal Of Pathology · doi:10.2353/ajpath.2006.051358 · Cited by 53
Self-citationSignal pathways mediating oxytocin stimulation of prostaglandin synthesis in select target cells
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Oxytocin and vasopressin 1a receptor gene expression in the cycling or pregnant human uterus
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Effects of Prostanoid EP Agonists on Mouse Intraocular Pressure
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Clinical Chemistry of the Laboratory Mouse
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“, 1997) as well as FP (Sugimoto et al., 1997) and EP2 (Kennedy et al.”
BackgroundTargeted Reduction of Oxytocin Expression Provides Insights into its Physiological Roles
Young, W. S., Shepard, E. A., DeVries, A. C., Zimmer, A., LaMarca, M. E., Ginns, E. I., Amico, J. A., Nelson, R. J., Hennighausen, L. G., & Wagner, K. (1998) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-4871-3_30 · Cited by 51
Overexpression of SK3 Channels Dampens Uterine Contractility to Prevent Preterm Labor in Mice1
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“For example, delayed delivery due to a failure of luteolysis or cervical ripening occurs in knockout mice, in which the genes encoding cyclooxygenase 1 [2], cytosolic phospholipase A 2 [3], the PGF 2a receptor [4], or 5a reductase type 1 [5] are disrupted.”
BackgroundEffect of Bimatoprost on Intraocular Pressure in Prostaglandin FP Receptor Knockout Mice
Crowston, J. G., Lindsey, J. D., Morris, C. A., Wheeler, L. A., Medeiros, F. A., & Weinreb, R. N. (2005) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.05-0723 · Cited by 49
Parturition and Recruitment of Macrophages in Cervix of Mice Lacking the Prostaglandin F Receptor1
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“mice, even though progesterone in circulation remained elevated [4, 38].”
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Self-citationMisregulated Progesterone Secretion and Impaired Pregnancy in Cyp11a1 Transgenic Mice1
Chien, Y., Cheng, W.-C., Wu, M., Jiang, S., Shen, C.-K. J., & Chung, B. (2013) · Biology of Reproduction · doi:10.1095/biolreprod.113.110833 · Cited by 49
“It also prevents uterine contraction to maintain pregnancy [7–10].”
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Hall, T., Kim, H., Dabbah, M., Myers, J., Crawford, J. C., Morales‐Hernández, A., Caprio, C., Sriram, P., Kooienga, E., Derecka, M., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33092-4 · Cited by 49
Metadata
- Authors
- Sugimoto, Y., Yamasaki, A., Segi, E., Tsuboi, K., Aze, Y., Nishimura, T., Oida, H., Yoshida, N., Tanaka, T., Katsuyama, M., Hasumoto, K.-Y., Murata, T., Hirata, M., Ushikubi, F., Negishi, M., Ichikawa, A., & Narumiya, S.
- Affiliations
- Kyoto University (JP)
- Y. Sugimoto, A. Yamasaki, E. Segi, K. Tsuboi, M. Katsuyama, K. Hasumoto, M. Negishi, A. Ichikawa, Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Kyoto 606, Japan.
- Corresponding author
- Ichikawa, Atsushi
- ORCID
- Venue
- Science
- Published
- 1997-08
- Volume
- 277
- Issue
- 5326
- Pages
- 681-683
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2142980049
- Cited by
- 608
- References
- 16
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 11 · 2023: 10 · 2022: 12 · 2021: 12 · 2020: 24 · 2019: 19 · 2018: 18 · 2017: 12 · 2016: 17 · 2015: 17 · 2014: 21 · 2013: 15 · 2012: 11
- FWCI
- 85.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Reproductive Physiology in Livestock
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- childbirth, prostaglandin F2alpha, FP receptor, oxytocin receptor, luteolysis, progesterone, ovariectomy, luteal cells, pregnancy, knockout mice, estrous cycle
- MeSH terms
- Animals, Corpus Luteum, Female, Heterozygote, Homozygote, Labor, Obstetric, Male, Mice, Inbred C57BL, Ovariectomy, Oxytocin, Pregnancy, Progesterone, Receptors, Prostaglandin, Uterine Contraction, Uterus, Dinoprost, Receptors, Oxytocin, Gene Targeting, Mice
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