Regulation of Pregnancy: Evidence for Major Roles by the Uterine and Placental Kisspeptin/KISS1R Signaling Systems

Radovick, Sally; Babwah, Andy V.

doi:10.1055/s-0039-3400966

Cited by 20 publications

(11 citation statements)

References 100 publications

(130 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This indicates a potential role of kisspeptin in the preparation of endometrial tissue for implantation. Kisspeptin knockout mice exhibit thin, weak uteri with almost no endometrial glands, suggesting kisspeptin is an important regulator of normal endometrial development [34]. Kisspeptin may also act as a mediator that facilitates implantation of the growing embryo to the uterine wall.…”

Section: Kisspeptin In the Luteal Phase And Implantationmentioning

confidence: 99%

“…Kisspeptin may also act as a mediator that facilitates implantation of the growing embryo to the uterine wall. It has been shown that exogenous kisspeptin administration strengthens adhesion of kisspeptin-expressing trophoblast cells to collagen present in uterine tissue [34]. Immediately after implantation, kisspeptin levels are known to rise; this suggests involvement of kisspeptin during the decidualization process [35].…”

Section: Kisspeptin In the Luteal Phase And Implantationmentioning

confidence: 99%

“…Kisspeptin also supports the adhesion of extravillous trophoblasts to the endometrium, which inhibits migration [38]. This careful balance between invasion and the prevention of invasion is essential to the placentation process as well as the appropriate remodeling of the maternal uterine wall [34]. As the placenta develops throughout pregnancy, it exhibits a pattern of kisspeptin expression that follows a circadian rhythm [39].…”

Section: Kisspeptin In the Luteal Phase And Implantationmentioning

confidence: 99%

“…Matjila et al investigated the relationship between maternal kisspeptin levels and placental kisspeptin expression in preeclamptic pregnancies -they found that preeclamptic placentas demonstrated high kisspeptin expression but low maternal kisspeptin levels [30]. It is speculated that elevated kisspeptin expression in diseased placentas may inhibit trophoblast invasion and contribute to the development of preeclampsia [30,34]. Kisspeptin therefore has potential to offer predictive information about the risk of preeclampsia.…”

Section: Kisspeptin In Pregnancymentioning

confidence: 99%

See 3 more Smart Citations

The Role of Kisspeptin in the Ovarian Cycle, Pregnancy, and Fertility

Ahart¹,

Phillips²,

Wolfe³

et al. 2021

Infertility and Assisted Reproduction

View full text Add to dashboard Cite

Kisspeptins are a group of neuropeptides with regulatory functions related to puberty, fertility, and reproduction. They are primarily produced by hypothalamic nuclei and are thought to regulate the activity of neurons that produce gonadotropin-releasing hormone. They are also expressed by placental syncytiotrophoblasts in developing pregnancies and are likely involved in the processes of trophoblast invasion and placentation. Similarly to beta-hCG, kisspeptins are found in maternal plasma during the first trimester of pregnancy and increase proportionately with gestational age. Because of their role in implantation, there is currently interest in the use of kisspeptins as minimally invasive biomarkers. It is suspected that maternal kisspeptin levels have diagnostic potential in identifying viable early pregnancies.

show abstract

Section: Kisspeptin In the Luteal Phase And Implantationmentioning

confidence: 99%

Section: Kisspeptin In the Luteal Phase And Implantationmentioning

confidence: 99%

Section: Kisspeptin In the Luteal Phase And Implantationmentioning

confidence: 99%

Section: Kisspeptin In Pregnancymentioning

confidence: 99%

See 2 more Smart Citations

The Role of Kisspeptin in the Ovarian Cycle, Pregnancy, and Fertility

Ahart¹,

Phillips²,

Wolfe³

et al. 2021

Infertility and Assisted Reproduction

View full text Add to dashboard Cite

show abstract

“…LGR4 couples to Ga s (and thereby stimulates adenylyl cyclase activity and cAMP formation), LPAR3 couples to Ga q/11 (and thereby stimulates phospholipase C activity and diacyl glycerol formation and Ca 2þ mobilization) and Ga i/0 inhibits adenylyl cyclase activity (10), whereas KISS1R couples to Ga q/11 (10,11). Deletion of these receptors in the mouse revealed critical roles for GPCRs in the acquisition of uterine receptivity, embryo implantation, and/or endometrial decidualization (3)(4)(5)(6)(7)12).…”

mentioning

confidence: 99%

Uterine Gpr83 mRNA is highly expressed during early pregnancy and GPR83 mediates the actions of PEN in endometrial and non-endometrial cells

et al. 2020

Self Cite

View full text Add to dashboard Cite

Objective: To characterize the expression and signaling of uterine GPR83 in vivo in the nonpregnant and pregnant mouse and in vitro in human endometrial and nonendometrial cells. Design: Controlled laboratory study. Setting: Not applicable. Patients: Not applicable. Interventions: None. Main Outcome Measures: Expression of uterine Gpr83 was determined by quantitative polymerase chain reaction throughout the estrous cycle and during early pregnancy in ovarian-stimulated and nonÀovarian-stimulated mice and pregnant and pseudopregnant mice. Expression was also determined in ovariectomized mice after the administration of oil, E2, P4, or E2 þ P4 and in stromal cells following 6 days of in vitro decidualization. GPR83 signaling was studied in human endometrial and embryonic kidney cell lines. Cells were treated by PEN, a GPR83 ligand, and PEN-induced extracellular signal-regulated kinase (ERK) phosphorylation was assayed under conditions that blocked Ga q/11 and/or b-arrestin signaling. Results: Uterine Gpr83 is expressed throughout the estrous cycle and during early pregnancy; expression increases dramatically at the time of uterine receptivity, embryo implantation, and stromal cell decidualization. In the ovariectomized mouse, hormone add-back reveals that Gpr83 expression is highly responsive to the combined treatment of E2 and P4, and studies in the ovarian-stimulated mouse show that expression is also very sensitive to changes in E2 and P4 and is therefore tightly regulated by E2 and P4. At the implantation site, expression is elevated up to D6 of pregnancy and then declines rapidly on D7 and D8, suggesting that if there is any involvement in decidualization, it is likely associated with primary but not secondary stromal cell decidualization. This premise was supported by the observation that stromal cell decidualization in vitro progresses with a decline in Gpr83 expression. In ERa/ PR-expressing endometrial Ishikawa cells, GPR83 mediates PEN signals in a Ga q/11-dependent manner, and studies conducted in HEK 293 cells lacking b-arrestin revealed that GPR83 also signals via a b-arrestinÀdependent manner. When signaling by either one or both pathways is downregulated, cells exhibit a major reduction in responsiveness to PEN treatment, demonstrating that signaling by both pathways is significant. Conclusion: We hypothesize that PEN/GPR83 signaling regulates uterine receptivity, embryo implantation, and primary stromal cell decidualization by coupling to Ga q/11-and b-arrestinÀdependent pathways.

show abstract