ATR function is indispensable to allow proper mammalian follicle development

Pacheco, Sarai; Maldonado-Linares, Andros; Garcia-Caldés, Montserrat; Roig, Ignasi

doi:10.1007/s00412-019-00723-7

Cited by 9 publications

(7 citation statements)

References 33 publications

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“…To test this, the number of γH2AX patches was counted, as a surrogate of unrepaired DSBs [26], in control and Chk2 mutant oocytes at different stages of meiotic prophase. As mentioned earlier and described elsewhere [26,28], wild-type oocytes at pachynema presented multiple unrepaired DSBs. Importantly, Chk2 mutant pachytene-stage oocytes had significantly more patches of γH2AX than did control cells (p<0.0001 T-test, Fig 1, S1 Table and S1 Data).…”

Section: Chk2 Mutant Fetal Ovaries Accumulate Oocytes With More Unrepsupporting

confidence: 63%

“…Mammalian gametogenesis is characterized by a marked sexual dimorphism [25]. One of many examples is found in the distinct control of meiotic recombination that occurs in mammalian oocytes, as compared with spermatocytes [22,[26][27][28]. While spermatocytes repair most DSBs by mid-pachynema, the vast majority of human oocytes still present multiple unrepaired DSBs at the same stage.…”

Section: Introductionmentioning

confidence: 99%

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The DNA damage response is required for oocyte cyst breakdown and follicle formation in mice

et al. 2020

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Mammalian oogonia proliferate without completing cytokinesis, forming cysts. Within these, oocytes differentiate and initiate meiosis, promoting double-strand break (DSBs) formation, which are repaired by homologous recombination (HR) causing the pairing and synapsis of the homologs. Errors in these processes activate checkpoint mechanisms, leading to apoptosis. At the end of prophase I, in contrast with what is observed in spermatocytes, oocytes accumulate unrepaired DSBs. Simultaneously to the cyst breakdown, there is a massive oocyte death, which has been proposed to be necessary to enable the individualization of the oocytes to form follicles. Based upon all the above-mentioned information, we hypothesize that the apparently inefficient HR occurring in the oocytes may be a requirement to first eliminate most of the oocytes and enable cyst breakdown and follicle formation. To test this idea, we compared perinatal ovaries from control and mutant mice for the effector kinase of the DNA Damage Response (DDR), CHK2. We found that CHK2 is required to eliminate ~50% of the fetal oocyte population. Nevertheless, the number of oocytes and follicles found in Chk2-mutant ovaries three days after birth was equivalent to that of the controls. These data revealed the existence of another mechanism capable of eliminating oocytes. In vitro inhibition of CHK1 rescued the oocyte number in Chk2-/- mice, implying that CHK1 regulates postnatal oocyte death. Moreover, we found that CHK1 and CHK2 functions are required for the timely breakdown of the cyst and to form follicles. Thus, we uncovered a novel CHK1 function in regulating the oocyte population in mice. Based upon these data, we propose that the CHK1- and CHK2-dependent DDR controls the number of oocytes and is required to properly break down oocyte cysts and form follicles in mammals.

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Section: Chk2 Mutant Fetal Ovaries Accumulate Oocytes With More Unrepsupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

The DNA damage response is required for oocyte cyst breakdown and follicle formation in mice

et al. 2020

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“…Chociaż rola kinazy Chk2 w sygnalizacji uszkodzeń DNA w oocycie również została wykazana [38,43] , to dokładny mechanizm jej aktywacji pozostaje nieznany. W porównaniu do komórek mitotycznych kolejną różnicą w funkcjonowaniu punktu kontrolnego G2/M w oocytach jest brak zaangażowania kinazy ATR [44,45].…”

Section: Mechanizmy Odpowiedzialne Za Integralność Materiału Genetycznego Oocytówunclassified

Komórkowe mechanizmy zapewniające jakość żeńskich komórek rozrodczych ssaków

Polanski¹,

Gąsior²

2022

Postepy Biochem

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Gamety są skrajnie zróżnicowanymi komórkami, które uczestnicząc w procesie zapłodnienia dają początek nowemu organizmowi. Rolą w pełni funkcjonalnej gamety, oprócz umożliwienia zapłodnienia, jest także zapewnienie pełnego niezakłóconego rozwój osobnika. Celem niniejszego artykuł jest przybliżenie funkcjonujących podczas oogenezy ssaków mechanizmów, które zapewniają właściwy przebieg procesów rozwojowych po zapłodnieniu oraz jakość przekazanego potomstwu materiału dziedzicznego.

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“…In addition, ATR does not seem to affect DSB numbers in mouse spermatocytes suggesting the balance of DSBs is regulated by a different mechanism in mice ( Widger et al, 2018 ). There is no evidence that ATM or ATR are important for regulating DSB numbers in mouse oocytes ( Pacheco et al, 2019 ) though in both oocytes and spermatocytes, ATM and ATR play roles in the DNA damage checkpoint and elimination of germ cells (see section “Elimination of Oocytes With Defective DNA Repair or Synapsis”). Regulation of DSB formation in mammalian oocytes may involve another kinase or feedback may be provided by factors detecting synapsis.…”

Section: Recombination: Formation and Repair Of Double-strand Breaksmentioning

confidence: 99%

Regulation of Meiotic Prophase One in Mammalian Oocytes

Wang

Pepling

2021

Front. Cell Dev. Biol.

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In female mammals, meiotic prophase one begins during fetal development. Oocytes transition through the prophase one substages consisting of leptotene, zygotene, and pachytene, and are finally arrested at the diplotene substage, for months in mice and years in humans. After puberty, luteinizing hormone induces ovulation and meiotic resumption in a cohort of oocytes, driving the progression from meiotic prophase one to metaphase two. If fertilization occurs, the oocyte completes meiosis two followed by fusion with the sperm nucleus and preparation for zygotic divisions; otherwise, it is passed into the uterus and degenerates. Specifically in the mouse, oocytes enter meiosis at 13.5 days post coitum. As meiotic prophase one proceeds, chromosomes find their homologous partner, synapse, exchange genetic material between homologs and then begin to separate, remaining connected at recombination sites. At postnatal day 5, most of the oocytes have reached the late diplotene (or dictyate) substage of prophase one where they remain arrested until ovulation. This review focuses on events and mechanisms controlling the progression through meiotic prophase one, which include recombination, synapsis and control by signaling pathways. These events are prerequisites for proper chromosome segregation in meiotic divisions; and if they go awry, chromosomes mis-segregate resulting in aneuploidy. Therefore, elucidating the mechanisms regulating meiotic progression is important to provide a foundation for developing improved treatments of female infertility.

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ATR function is indispensable to allow proper mammalian follicle development

Cited by 9 publications

References 33 publications

The DNA damage response is required for oocyte cyst breakdown and follicle formation in mice

The DNA damage response is required for oocyte cyst breakdown and follicle formation in mice

Komórkowe mechanizmy zapewniające jakość żeńskich komórek rozrodczych ssaków

Regulation of Meiotic Prophase One in Mammalian Oocytes

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