Elevated Maternal Serum Relaxin Concentrations Throughout Pregnancy in Singleton Gestations After Superovulation

Mushayandebvu, T

doi:10.1016/s0029-7844(98)00091-x

Cited by 31 publications

(17 citation statements)

References 13 publications

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“…Similarly, many women who undergo autologous frozen embryo transfer frequently do so in a medicated cycle involving hypothalamic-pituitary suppression. On the other hand, women undergoing ovarian stimulation, IVF and fresh embryo transfer have multiple corpora lutea, and thus, elevated levels of circulating relaxin (Mushayandebvu et al, 1998). Relative to spontaneous conceptions, we anticipate subdued changes in the maternal circulation ('hypodynamic') of women conceiving by ART with absent corpus luteum and circulating relaxin, particularly during early pregnancy, consistent with the rat studies (Conrad and Baker, 2013).…”

Section: Role Of Relaxin In the Cardiovascular Adaptations To Pregnancysupporting

confidence: 78%

G-Protein-coupled receptors as potential drug candidates in preeclampsia: targeting the relaxin/insulin-like family peptide receptor 1 for treatment and prevention

Conrad

2016

Hum. Reprod. Update

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There is a strong scientific rationale for RXFP1 activation in severe preeclampsia by administration of relaxin, relaxin analogs or small molecule mimetics, in order to mollify the disease pathogenesis for safe prolongation of pregnancy, thus allowing time for more complete fetal maturation, which is a primary therapeutic endpoint in treating the disease. In light of recent data implicating deficient or defective decidualization as a potential etiological factor in preeclampsia and the capacity of relaxin to promote endometrial maturation, the prophylactic application of relaxin to reduce the risk of preeclampsia is a plausible therapeutic approach to consider. Finally, given its pleiotropic and beneficial attributes particularly in the cardiovascular system, relaxin, although traditionally considered as a 'pregnancy' hormone, is likely to prove salutary for several disease indications in the non-pregnant population.

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Section: Role Of Relaxin In the Cardiovascular Adaptations To Pregnancysupporting

confidence: 78%

G-Protein-coupled receptors as potential drug candidates in preeclampsia: targeting the relaxin/insulin-like family peptide receptor 1 for treatment and prevention

Conrad

2016

Hum. Reprod. Update

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“…In animal models, it was shown that the involvement of relaxin in cervical collagenolysis decreased cervical resistance and led to consequent cervical ripening (19). Compared with naturally conceived pregnancies, those conceived through ovulation induction had higher circulating levels of relaxin not only in the first trimester (20) but also in the second and third trimesters (21). Finally, higher relaxin levels observed at the third trimester were significantly associated with PTB (18).…”

Section: Discussionmentioning

confidence: 99%

Assisted reproductive technology and the risk of preterm birth among primiparas

Dunietz

Holzman

McKane

et al. 2015

Fertility and Sterility

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Objective To investigate the risk of preterm birth among liveborn singletons to primiparas who conceived with assisted reproductive technology (ART) using four mutually exclusive categories of infertility (female infertility only, male infertility only, female and male infertility, and unexplained infertility) and to examine preterm birth risk along the gestational age continuum. Design Retrospective cohort study. Setting Not applicable. Patient(s) Singletons born to primiparas who conceived with or without ART. Intervention(s) None. Main Outcome Measure(s) Preterm (<37 weeks’ gestation) and preterm/early term birth <39 weeks’ gestation). Result(s) For the male infertility only, female infertility only, combined male and female infertility, and unexplained infertility groups, ART-conceived singletons were significantly more likely than non-ART singletons to be born preterm: adjusted odds ratio (aOR) 1.24 (95% CI, 1.13, 1.37), aOR 1.60 (95% CI, 1.50, 1.70), aOR 1.49 (95% CI, 1.35, 1.64), and aOR 1.26 (1.12, 1.43) respectively. Among infants whose mothers were diagnosed with infertility, the odds of preterm birth were highest between 28–30 weeks [female infertility only, aOR 1.95 (95% CI, 1.59, 2.39); male and female infertility: 2.21 (95% CI, 1.62, 3.00)] compared with infants in the general population. Within the ART population, singletons of couples with female infertility only were more likely to be born preterm than singletons born to couples with other infertility diagnoses. Conclusion(s) Among singleton births to primiparas, those conceived with ART had an increased risk for preterm birth, even when only the male partner had been diagnosed with infertility. The risk of preterm birth for ART-conceived infants whose mothers were diagnosed with infertility included the earliest deliveries.

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“…Thus, in the presence of a subclinical infection, if endogenous RLN levels were elevated, such as in multifetal pregnancies [13] or in singleton pregnancies after superovulation [14], RLN could significantly affect the outcome of the pregnancy. This is in addition to it being able to cause a sterile inflammatory response in the absence of any infection [16].…”

Section: Discussionmentioning

confidence: 99%

“…Thus, in patients with more than one corpus luteum, as in some twin gestations [13], or in superovulation [14], the higher than normal systemic RLN somehow contributes to PTB, although the mechanism involved is currently unknown. We have shown that the intrauterine expression of RLN is not increased in patients with severe chorioamnionitis, despite significantly increased IL6 expression [15].…”

Section: Introductionmentioning

confidence: 99%

Relaxin augments the inflammatory IL6 response in the choriodecidua

2012

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Intrauterine infection frequently leads to preterm birth (PTB), with the pathophysiology involving activation of the innate immune system and its associated inflammatory response. The choriodecidua produces relaxin (RLN) and elevated levels are associated with preterm premature rupture of the fetal membranes. However, it is not increased in bacterially-mediated PTB, but may act as an endogenous sterile inflammatory mediator. Elevated systemic RLN levels from the corpus luteum are also associated with PTB, but the mechanism is unknown. In clinical obstetrics, intrauterine inflammation or infection can coexist with elevated RLN. Therefore, in this study, we further characterized the effects of RLN alone or together with an inflammatory mediator on the production of IL1B, CSF2 (GM-CSF), IL6, IL8 and TNF, from chorionic cytotrophoblasts (CyT), decidual fibroblasts (DF) and stromal cells (DSC), using interleukin-1 beta (IL1B) to mimic sterile inflammation or lipopolysaccharide (LPS) for bacterial infection. Endogenous differences between the cells showed that the CyT expressed more and the RXFP1, its receptor RXFP1 splice variant D. CyT also showed the most robust cAMP response to RLN with increased IL6 secreted after 4 h, preceded by increased transcription at 1 h, likely due to activation of RXFP1 and cAMP. When all cell types were treated with IL1B and RLN, RLN augmented secretion of IL6 and IL8 from CyT and DF, but not DSC. Similarly, RLN augmented LPS-induced IL6 secretion from CyT and DF. Despite the structural similarity between TLR4 and RXFP1, blocking TLR4 in CyT had no effect on RLN-induced IL6 secretion, suggesting specific activation of RXFP1. Thus, we have shown that in the presence of a low level of intrauterine inflammation/infection, elevated RLN could act on the CyT and DF to augment the inflammatory response, contributing to the pathophysiology of PTB.

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Elevated Maternal Serum Relaxin Concentrations Throughout Pregnancy in Singleton Gestations After Superovulation

Cited by 31 publications

References 13 publications

G-Protein-coupled receptors as potential drug candidates in preeclampsia: targeting the relaxin/insulin-like family peptide receptor 1 for treatment and prevention

G-Protein-coupled receptors as potential drug candidates in preeclampsia: targeting the relaxin/insulin-like family peptide receptor 1 for treatment and prevention

Assisted reproductive technology and the risk of preterm birth among primiparas

Relaxin augments the inflammatory IL6 response in the choriodecidua

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