Effects of highly purified urinary FSH and human menopausal FSH on uterine myoelectrical dynamics

Hasçalık, Şeyma; Çelik, Önder; Tağluk, M. Emin; Yıldırım, Ayşe; Aydın, Engin

doi:10.1093/molehr/gap076

Cited by 11 publications

(13 citation statements)

References 20 publications

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“…Investigators also have observed FSHR protein and mRNA expression in nongonadal tissues, including uterus and cervix [29], [30], [31]. In these tissues, FSHR may mediate uterine relaxation, as suggested by FSH's ability to modify electrical signaling in the myometrium, independent of estrogen and progesterone [29]. Padmanabhan and colleagues [34] noted a progressive rise in bioactive serum FSH levels during pregnancy.…”

Section: Resultsmentioning

confidence: 99%

“…FSH is secreted from the pituitary and, in females, acts primarily on receptors in the ovaries to stimulate follicle development and synthesis of estrogens. Investigators also have observed FSHR protein and mRNA expression in nongonadal tissues, including uterus and cervix [29], [30], [31]. In these tissues, FSHR may mediate uterine relaxation, as suggested by FSH's ability to modify electrical signaling in the myometrium, independent of estrogen and progesterone [29].…”

Section: Resultsmentioning

confidence: 99%

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An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing

et al. 2011

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Coordination of fetal maturation with birth timing is essential for mammalian reproduction. In humans, preterm birth is a disorder of profound global health significance. The signals initiating parturition in humans have remained elusive, due to divergence in physiological mechanisms between humans and model organisms typically studied. Because of relatively large human head size and narrow birth canal cross-sectional area compared to other primates, we hypothesized that genes involved in parturition would display accelerated evolution along the human and/or higher primate phylogenetic lineages to decrease the length of gestation and promote delivery of a smaller fetus that transits the birth canal more readily. Further, we tested whether current variation in such accelerated genes contributes to preterm birth risk. Evidence from allometric scaling of gestational age suggests human gestation has been shortened relative to other primates. Consistent with our hypothesis, many genes involved in reproduction show human acceleration in their coding or adjacent noncoding regions. We screened >8,400 SNPs in 150 human accelerated genes in 165 Finnish preterm and 163 control mothers for association with preterm birth. In this cohort, the most significant association was in FSHR, and 8 of the 10 most significant SNPs were in this gene. Further evidence for association of a linkage disequilibrium block of SNPs in FSHR, rs11686474, rs11680730, rs12473870, and rs1247381 was found in African Americans. By considering human acceleration, we identified a novel gene that may be associated with preterm birth, FSHR. We anticipate other human accelerated genes will similarly be associated with preterm birth risk and elucidate essential pathways for human parturition.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing

et al. 2011

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“…A previous study identified ZEB1 as a key suppressor of genes involved in uterine contraction in both humans and mice [36]. FSH, the ligand recognized by FSHR, is known to modulate the electrical signaling property of the uterine muscle [20]. Thus, the weaker binding of ZEB1 in the presence of the G allele may cause de-repression of FSHR.…”

Section: Resultsmentioning

confidence: 99%

Fine-Mapping an Association of FSHR with Preterm Birth in a Finnish Population

et al. 2013

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Preterm birth is a complex disorder defined by gestations of less than 37 weeks. While preterm birth is estimated to have a significant genetic component, relative few genes have been associated with preterm birth. Polymorphism in one such gene, follicle-stimulating hormone receptor (FSHR), has been associated with preterm birth in Finnish and African American mothers but not other populations. To refine the genetic association of FSHR with preterm birth we conducted a fine-mapping study at the FSHR locus in a Finnish cohort. We sequenced a total of 44 kb, including protein-coding and conserved non-coding regions, in 127 preterm and 135 term mothers. Overall, we identified 288 single nucleotide variants and 65 insertion/deletions of 1–2 bp across all subjects. While no common SNPs in protein-coding regions were associated with preterm birth, including one previously associated with timing of fertilization, multiple SNPs spanning the first and second intron showed the strongest associations. Analysis of the associated SNPs revealed that they form both a protective (OR = 0.50, 95% CI = 0.25–0.93) as well as a risk (OR = 1.89, 95% CI = 1.08–3.39) haplotype with independent effects. In these haplotypes, two SNPs, rs12052281 and rs72822025, were predicted to disrupt ZEB1 and ELF3 transcription factor binding sites, respectively. Our results show that multiple haplotypes at FSHR are associated with preterm birth and we discuss the frequency and structure of these haplotypes outside of the Finnish population as a potential explanation for the absence of FSHR associations in some populations.

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“…Not only antibiotics but also other drugs have been studied in respect to their effects on myometrial dynamics. It has been shown that human menopausal gonadotropin and highly purified urinary FSH supress the myoelectrical signals and provides uterine quiescence [18]. It was also demonstrated that estrogen, progesterone and hCG reduce the frequency of uterine contractions [19].…”

Section: Discussionmentioning

confidence: 99%

Nitrofurantoin inhibits contractions of myometrium isolated from pregnant and nonpregnant rats

Kavak¹,

Kacar²,

Kavak³

et al. 2018

Med-Science

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We aimed to investigate the effects of nitrofurantoin, a commonly used antibiotic for urinary tract infections, on spontaneous contractions of rat myometrium isolated from 16-day pregnant and nonpregnant rats. Myometrial strips were suspended in a standard organ bath and after the manifestation of spontaneous contractions under 1 g of resting tension, nitrofurantoin was applied to the organ bath as 50, 250 and 500 µM doses. Amplitude and frequency of contractions were recorded for 20 minutes before and after application of the drug. The bath was washed to remove the drug from the medium after recording the effect of each dose and the contractions were enrolled again to show the reversible effect of the drug. The effects of nitrofurantoin on amplitude (milligrams) and frequency of spontaneous contractions were evaluated. Data were statistically analyzed using the Student's t test and p<0.05 was considered to be statistically significant. Nitrofurantoin inhibited spontaneous contractions in a dose dependent manner. Although both the frequency and amplitude of contractions were significantly inhibited at all doses, the inhibition of contractions were 100% at 500 µM dose, which corresponds to the dose used for prophylaxis in clinical practice. The results of this in vitro study indicated that nitrofurantoin inhibits spontaneous contractions of myometrium isolated from pregnant and nonpregnant rats.

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Effects of highly purified urinary FSH and human menopausal FSH on uterine myoelectrical dynamics

Cited by 11 publications

References 20 publications

An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing

An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing

Fine-Mapping an Association of FSHR with Preterm Birth in a Finnish Population

Nitrofurantoin inhibits contractions of myometrium isolated from pregnant and nonpregnant rats

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