FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4205655376> ?p ?o ?g. }

• W4205655376 endingPage "821" @default.
• W4205655376 startingPage "806" @default.
• W4205655376 abstract "Does direct kisspeptin signaling in the oocyte have a role in the control of follicular dynamics and ovulation?Kisspeptin signaling in the oocyte plays a relevant physiological role in the direct control of ovulation; oocyte-specific ablation of kisspeptin receptor, Gpr54, induces a state of premature ovulatory failure in mice that recapitulates some features of premature ovarian insufficiency (POI).Kisspeptins, encoded by the Kiss1 gene, are essential for the control of ovulation and fertility, acting primarily on hypothalamic GnRH neurons to stimulate gonadotropin secretion. However, kisspeptins and their receptor, Gpr54, are also expressed in the ovary of different mammalian species, including humans, where their physiological roles remain contentious and poorly characterized.A novel mouse line with conditional ablation of Gpr54 in oocytes, named OoGpr54-/-, was generated and studied in terms of follicular and ovulatory dynamics at different age-points of postnatal maturation. A total of 59 OoGpr54-/- mice and 47 corresponding controls were analyzed. In addition, direct RNA sequencing was applied to ovarian samples from 8 OoGpr54-/- and 7 control mice at 6 months of age, and gonadotropin priming for ovulatory induction was conducted in mice (N = 7) from both genotypes.Oocyte-selective ablation of Gpr54 in the oocyte was achieved in vivo by crossing a Gdf9-driven Cre-expressing transgenic mouse line with a Gpr54 LoxP mouse line. The resulting OoGpr54-/- mouse line was subjected to phenotypic, histological, hormonal and molecular analyses at different age-points of postnatal maturation (Day 45, and 2, 4, 6 and 10-11 months of age), in order to characterize the timing of puberty, ovarian follicular dynamics and ovulation, with particular attention to identification of features reminiscent of POI. The molecular signature of ovaries from OoGpr54-/- mice was defined by direct RNA sequencing. Ovulatory responses to gonadotropin priming were also assessed in OoGpr54-/- mice.Oocyte-specific ablation of Gpr54 caused premature ovulatory failure, with some POI-like features. OoGpr54-/- mice had preserved puberty onset, without signs of hypogonadism. However, already at 2 months of age, 40% of OoGpr54-/- females showed histological features reminiscent of ovarian failure and anovulation. Penetrance of the phenotype progressed with age, with >80% and 100% of OoGpr54-/- females displaying complete ovulatory failure by 6- and 10 months, respectively. This occurred despite unaltered hypothalamic Gpr54 expression and gonadotropin levels. Yet, OoGpr54-/- mice had decreased sex steroid levels. While the RNA signature of OoGpr54-/- ovaries was dominated by the anovulatory state, oocyte-specific ablation of Gpr54 significantly up- or downregulated of a set of 21 genes, including those encoding pituitary adenylate cyclase-activating polypeptide, Wnt-10B, matrix-metalloprotease-12, vitamin A-related factors and calcium-activated chloride channel-2, which might contribute to the POI-like state. Notably, the anovulatory state of young OoGpr54-/- mice could be rescued by gonadotropin priming.N/A. .Conditional ablation of Gpr54 in oocytes unambiguously caused premature ovulatory failure in mice; yet, the ultimate molecular mechanisms for such state of POI can be only inferred on the basis of RNAseq data and need further elucidation, since some of the molecular changes observed in OoGpr54-/- ovaries were secondary to the anovulatory state. Direct translation of mouse findings to human disease should be made with caution since, despite the conserved expression of Kiss1/kisspeptin and Gpr54 in rodents and humans, our mouse model does not recapitulate all features of common forms of POI.Deregulation of kisspeptin signaling in the oocyte might be an underlying, and previously unnoticed, cause for some forms of POI in women.This work was primarily supported by a grant to M.P. and M.T.-S. from the FiDiPro (Finnish Distinguished Professor) Program of the Academy of Finland. Additional financial support came from grant BFU2017-83934-P (M.T.-S.; Ministerio de Economía y Competitividad, Spain; co-funded with EU funds/FEDER Program), research funds from the IVIRMA International Award in Reproductive Medicine (M.T.-S.), and EFSD Albert Renold Fellowship Programme (S.T.R.). The authors have no conflicts of interest to declare in relation to the contents of this work.N/A." @default.
• W4205655376 created "2022-01-25" @default.
• W4205655376 creator A5002203416 @default.
• W4205655376 creator A5006291106 @default.
• W4205655376 creator A5023061026 @default.
• W4205655376 creator A5036575246 @default.
• W4205655376 creator A5043404151 @default.
• W4205655376 creator A5044864426 @default.
• W4205655376 creator A5052812534 @default.
• W4205655376 creator A5059068506 @default.
• W4205655376 creator A5060008004 @default.
• W4205655376 creator A5064220321 @default.
• W4205655376 creator A5079734591 @default.
• W4205655376 creator A5084965002 @default.
• W4205655376 creator A5091032474 @default.
• W4205655376 date "2022-01-17" @default.
• W4205655376 modified "2023-10-16" @default.
• W4205655376 title "Selective loss of kisspeptin signaling in oocytes causes progressive premature ovulatory failure" @default.
• W4205655376 cites W1495913478 @default.
• W4205655376 cites W1572601110 @default.
• W4205655376 cites W1591843063 @default.
• W4205655376 cites W1880891411 @default.
• W4205655376 cites W1967032043 @default.
• W4205655376 cites W1978752207 @default.
• W4205655376 cites W1979782649 @default.
• W4205655376 cites W1986118516 @default.
• W4205655376 cites W1992041715 @default.
• W4205655376 cites W1995380492 @default.
• W4205655376 cites W1998903859 @default.
• W4205655376 cites W2008613207 @default.
• W4205655376 cites W2010855604 @default.
• W4205655376 cites W2015603708 @default.
• W4205655376 cites W2018519788 @default.
• W4205655376 cites W2021607587 @default.
• W4205655376 cites W2021996823 @default.
• W4205655376 cites W2027421516 @default.
• W4205655376 cites W2030620540 @default.
• W4205655376 cites W2034168643 @default.
• W4205655376 cites W2039926087 @default.
• W4205655376 cites W2042324625 @default.
• W4205655376 cites W2043659942 @default.
• W4205655376 cites W2044431633 @default.
• W4205655376 cites W2060140841 @default.
• W4205655376 cites W2068817544 @default.
• W4205655376 cites W2073511974 @default.
• W4205655376 cites W2086517349 @default.
• W4205655376 cites W2087947221 @default.
• W4205655376 cites W2094471284 @default.
• W4205655376 cites W2110912300 @default.
• W4205655376 cites W2111824942 @default.
• W4205655376 cites W2115742485 @default.
• W4205655376 cites W2117243630 @default.
• W4205655376 cites W2119533233 @default.
• W4205655376 cites W2122588580 @default.
• W4205655376 cites W2124424992 @default.
• W4205655376 cites W2129067173 @default.
• W4205655376 cites W2130784408 @default.
• W4205655376 cites W2133369819 @default.
• W4205655376 cites W2141723861 @default.
• W4205655376 cites W2142686356 @default.
• W4205655376 cites W2150819167 @default.
• W4205655376 cites W2151954032 @default.
• W4205655376 cites W2157415584 @default.
• W4205655376 cites W2158217645 @default.
• W4205655376 cites W2160864692 @default.
• W4205655376 cites W2161426907 @default.
• W4205655376 cites W2165276620 @default.
• W4205655376 cites W2168757981 @default.
• W4205655376 cites W2170518484 @default.
• W4205655376 cites W2170737224 @default.
• W4205655376 cites W2195687926 @default.
• W4205655376 cites W2234709467 @default.
• W4205655376 cites W2262780773 @default.
• W4205655376 cites W2285998663 @default.
• W4205655376 cites W2316494606 @default.
• W4205655376 cites W2340098673 @default.
• W4205655376 cites W2398382881 @default.
• W4205655376 cites W2408827700 @default.
• W4205655376 cites W2490690636 @default.
• W4205655376 cites W2515590801 @default.
• W4205655376 cites W2528283024 @default.
• W4205655376 cites W2533993098 @default.
• W4205655376 cites W2574224286 @default.
• W4205655376 cites W2588080241 @default.
• W4205655376 cites W2606088168 @default.
• W4205655376 cites W2742961051 @default.
• W4205655376 cites W2773617182 @default.
• W4205655376 cites W2781886147 @default.
• W4205655376 cites W2799453916 @default.
• W4205655376 cites W2892286528 @default.
• W4205655376 cites W2979234953 @default.
• W4205655376 cites W2995142310 @default.
• W4205655376 cites W3132913291 @default.
• W4205655376 doi "https://doi.org/10.1093/humrep/deab287" @default.
• W4205655376 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35037941" @default.
• W4205655376 hasPublicationYear "2022" @default.
• W4205655376 type Work @default.
• W4205655376 citedByCount "11" @default.

• next