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Erschienen in: Journal of Assisted Reproduction and Genetics 5/2019

01.02.2019 | Assisted Reproduction Technologies

An integrated investigation of oocyte developmental competence: expression of key genes in human cumulus cells, morphokinetics of early divisions, blastulation, and euploidy

verfasst von: C. Scarica, D. Cimadomo, L. Dovere, A. Giancani, M. Stoppa, A. Capalbo, F. M. Ubaldi, L. Rienzi, R. Canipari

Erschienen in: Journal of Assisted Reproduction and Genetics | Ausgabe 5/2019

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Abstract

Purpose

To investigate the association of cumulus cell (CC)-related expression of a selected cluster of key genes (PTGS2, CAMK1D, HAS2, STC1, and EFNB2) with embryo development to blastocyst.

Methods

Exploratory study at a private clinic. Eighteen advanced maternal age patients were enrolled (37.3 ± 4.0 years). Seventy-five cumuli were collected, whose oocytes resulted in either developmental arrest (N = 33) or blastocyst formation (N = 42). The noninvasive CC gene expression was combined with time-lapse morphokinetic parameters and, for blastocysts, with qPCR-based aneuploidy testing on trophectoderm biopsies.

Results

The detection rate was 100% for all transcripts, but STC1 (96%) and CAMK1D (89%). Among amplified assays, CC mean expression levels of CAMK1D, PTGS2, and HAS2 were higher from oocytes that developed to blastocyst. No difference in CC key gene expression was reported between euploid (N = 21) and aneuploid (N = 21) blastocysts. Some timings of early embryo development were faster in embryos developing to blastocyst (time of pronuclei appearance and fading, division to two- and four-cells, first and second cell cycles). However, the generalized linear models outlined increasing CAMK1D expression levels as the strongest parameter associated with oocytes’ developmental potential from both a general (AUC = 0.78 among amplified samples) and an intrapatient perspectives (AUC = 0.9 among patients obtaining ≥ 2 zygotes from the cohort with different developmental outcomes).

Conclusions

CAMK1D level of expression in CCs associated with blastocyst development. If confirmed from larger studies in wider populations of patients, the investigation of CC key gene expression might suit IVF clinics not adopting blastocyst culture. Future investigations should clarify the role of CAMK1D in ovarian physiology and could provide novel insights on how oocytes gain competence during folliculogenesis.
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Literatur
1.
5.
Zurück zum Zitat Gardner DK. Blastocyst culture: toward single embryo transfers. Hum Fertil (Camb). 2000;3(4):229–37.CrossRef Gardner DK. Blastocyst culture: toward single embryo transfers. Hum Fertil (Camb). 2000;3(4):229–37.CrossRef
14.
23.
Zurück zum Zitat Eppig JJ. Oocyte control of ovarian follicular development and function in mammals. Reproduction. 2001;122(6):829–38.CrossRef Eppig JJ. Oocyte control of ovarian follicular development and function in mammals. Reproduction. 2001;122(6):829–38.CrossRef
26.
Zurück zum Zitat Kedem A, Fisch B, Garor R, Ben-Zaken A, Gizunterman T, Felz C, et al. Growth differentiating factor 9 (GDF9) and bone morphogenetic protein 15 both activate development of human primordial follicles in vitro, with seemingly more beneficial effects of GDF9. J Clin Endocrinol Metab. 2011;96(8):E1246–54. https://doi.org/10.1210/jc.2011-0410.CrossRefPubMed Kedem A, Fisch B, Garor R, Ben-Zaken A, Gizunterman T, Felz C, et al. Growth differentiating factor 9 (GDF9) and bone morphogenetic protein 15 both activate development of human primordial follicles in vitro, with seemingly more beneficial effects of GDF9. J Clin Endocrinol Metab. 2011;96(8):E1246–54. https://​doi.​org/​10.​1210/​jc.​2011-0410.CrossRefPubMed
36.
Zurück zum Zitat Wissing ML, Kristensen SG, Andersen CY, Mikkelsen AL, Host T, Borup R, et al. Identification of new ovulation-related genes in humans by comparing the transcriptome of granulosa cells before and after ovulation triggering in the same controlled ovarian stimulation cycle. Hum Reprod. 2014;29(5):997–1010. https://doi.org/10.1093/humrep/deu008.CrossRefPubMed Wissing ML, Kristensen SG, Andersen CY, Mikkelsen AL, Host T, Borup R, et al. Identification of new ovulation-related genes in humans by comparing the transcriptome of granulosa cells before and after ovulation triggering in the same controlled ovarian stimulation cycle. Hum Reprod. 2014;29(5):997–1010. https://​doi.​org/​10.​1093/​humrep/​deu008.CrossRefPubMed
40.
Zurück zum Zitat Rienzi L, Ubaldi F, Anniballo R, Cerulo G, Greco E. Preincubation of human oocytes may improve fertilization and embryo quality after intracytoplasmic sperm injection. Hum Reprod. 1998;13(4):1014–9.CrossRef Rienzi L, Ubaldi F, Anniballo R, Cerulo G, Greco E. Preincubation of human oocytes may improve fertilization and embryo quality after intracytoplasmic sperm injection. Hum Reprod. 1998;13(4):1014–9.CrossRef
45.
Zurück zum Zitat Gardner DK, Schoolcraft B. In vitro culture of human blastocyst. In: Jansen R, Mortimer D, editors. Towards reproductive certainty: infertility and genetics beyond. Carnforth: Parthenon Press; 1999. p. 377–88. Gardner DK, Schoolcraft B. In vitro culture of human blastocyst. In: Jansen R, Mortimer D, editors. Towards reproductive certainty: infertility and genetics beyond. Carnforth: Parthenon Press; 1999. p. 377–88.
48.
Zurück zum Zitat Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002;3(7):RESEARCH0034.CrossRef Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002;3(7):RESEARCH0034.CrossRef
50.
Zurück zum Zitat Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3(6):1101–8.CrossRef Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3(6):1101–8.CrossRef
60.
Zurück zum Zitat Eppig JJ. Prostaglandin E2 stimulates cumulus expansion and hyaluronic acid synthesis by cumuli oophori isolated from mice. Biol Reprod. 1981;25(1):191–5.CrossRef Eppig JJ. Prostaglandin E2 stimulates cumulus expansion and hyaluronic acid synthesis by cumuli oophori isolated from mice. Biol Reprod. 1981;25(1):191–5.CrossRef
61.
Zurück zum Zitat Hizaki H, Segi E, Sugimoto Y, Hirose M, Saji T, Ushikubi F, et al. Abortive expansion of the cumulus and impaired fertility in mice lacking the prostaglandin E receptor subtype EP(2). Proc Natl Acad Sci U S A. 1999;96(18):10501–6.CrossRef Hizaki H, Segi E, Sugimoto Y, Hirose M, Saji T, Ushikubi F, et al. Abortive expansion of the cumulus and impaired fertility in mice lacking the prostaglandin E receptor subtype EP(2). Proc Natl Acad Sci U S A. 1999;96(18):10501–6.CrossRef
62.
Zurück zum Zitat Lim H, Paria BC, Das SK, Dinchuk JE, Langenbach R, Trzaskos JM, et al. Multiple female reproductive failures in cyclooxygenase 2-deficient mice. Cell. 1997;91(2):197–208.CrossRef Lim H, Paria BC, Das SK, Dinchuk JE, Langenbach R, Trzaskos JM, et al. Multiple female reproductive failures in cyclooxygenase 2-deficient mice. Cell. 1997;91(2):197–208.CrossRef
66.
Zurück zum Zitat Salustri A, Yanagishita M, Hascall VC. Synthesis and accumulation of hyaluronic acid and proteoglycans in the mouse cumulus cell-oocyte complex during follicle-stimulating hormone-induced mucification. J Biol Chem. 1989;264(23):13840–7.PubMed Salustri A, Yanagishita M, Hascall VC. Synthesis and accumulation of hyaluronic acid and proteoglycans in the mouse cumulus cell-oocyte complex during follicle-stimulating hormone-induced mucification. J Biol Chem. 1989;264(23):13840–7.PubMed
67.
Zurück zum Zitat Salustri A, Ulisse S, Yanagishita M, Hascall VC. Hyaluronic acid synthesis by mural granulosa cells and cumulus cells in vitro is selectively stimulated by a factor produced by oocytes and by transforming growth factor-beta. J Biol Chem. 1990;265(32):19517–23.PubMed Salustri A, Ulisse S, Yanagishita M, Hascall VC. Hyaluronic acid synthesis by mural granulosa cells and cumulus cells in vitro is selectively stimulated by a factor produced by oocytes and by transforming growth factor-beta. J Biol Chem. 1990;265(32):19517–23.PubMed
Metadaten
Titel
An integrated investigation of oocyte developmental competence: expression of key genes in human cumulus cells, morphokinetics of early divisions, blastulation, and euploidy
verfasst von
C. Scarica
D. Cimadomo
L. Dovere
A. Giancani
M. Stoppa
A. Capalbo
F. M. Ubaldi
L. Rienzi
R. Canipari
Publikationsdatum
01.02.2019
Verlag
Springer US
Erschienen in
Journal of Assisted Reproduction and Genetics / Ausgabe 5/2019
Print ISSN: 1058-0468
Elektronische ISSN: 1573-7330
DOI
https://doi.org/10.1007/s10815-019-01410-3

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