Mutation analysis of NANOS3 in Brazilian women with primary ovarian failure

Sousa, Braian Lucas A.; Nishi, Mirian Yumie; Santos, Mariza Gerdulo; Brito, Vinícius Nahime; Domenice, Sorahia; Mendonca, Berenice B.

doi:10.6061/clinics/2016(12)03

Cited by 6 publications

(2 citation statements)

References 14 publications

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“…Although the structure of P100 is solved (Rother et al 1992), the molecular biology of PATL2 variants is otherwise unexplored. However, infertility-linked variants in another translational regulator, NANOS3, suggest that translational regulation may be a key pathogenic mechanism in infertility (Wu et al 2013, Santos et al 2014, Sousa et al 2016.…”

Section: R23mentioning

confidence: 99%

Meiosis interrupted: the genetics of female infertility via meiotic failure

et al. 2021

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Idiopathic or “unexplained” infertility represents as many as 30% of infertility cases worldwide. Conception, implantation, and term delivery of developmentally healthy infants require chromosomally normal (euploid) eggs and sperm. The crux of euploid egg production is error-free meiosis. Pathologic genetic variants dysregulate meiotic processes that occur during prophase I, meiotic resumption, chromosome segregation, and in cell-cycle regulation. This dysregulation can result in chromosomally abnormal (aneuploid) eggs. In turn, egg aneuploidy leads to a broad range of clinical infertility phenotypes, including primary ovarian insufficiency and early menopause, egg fertilization failure and embryonic developmental arrest, or recurrent pregnancy loss. Therefore, maternal genetic variants are emerging as infertility biomarkers, which could allow informed reproductive decision-making. Here, we select and deeply examine human genetic variants that likely cause dysregulation of critical meiotic processes in 14 female infertility-associated genes: SYCP3, SYCE1, TRIP13, PSMC3IP, DMC1, MCM8, MCM9, STAG3, PATL2, TUBB8, CEP120, AURKB, AURKC, and WEE2. We discuss the function of each gene in meiosis, explore genotype-phenotype relationships, and delineate the frequencies of infertility-associated variants.

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Section: R23mentioning

confidence: 99%

Meiosis interrupted: the genetics of female infertility via meiotic failure

et al. 2021

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“…NANOS3 gene mutations were found in a group of infertile men, but no causation was detected [11]. On the other hand, two out of four NANOS3 mutations were detected to be linked to premature ovarian insufficiency (POI) in infertile women [13][14][15][16]. Moreover, Santos et al demonstrated that one NANOS3 mutation linked to POI causes increased apoptosis of cultured cells, suggesting an anti-apoptotic role of human NANOS3 [14], as was shown for a mouse orthologue.…”

Section: Introductionmentioning

confidence: 95%

Human NANOS1 Represses Apoptosis by Downregulating Pro-Apoptotic Genes in the Male Germ Cell Line

Janecki

Ilaslan

Smialek

et al. 2020

IJMS

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While two mouse NANOS paralogues, NANOS2 and NANOS3, are crucial for maintenance of germ cells by suppression of apoptosis, the mouse NANOS1 paralogue does not seem to regulate these processes. Previously, we described a human NANOS1 p.[(Pro34Thr);(Ser83del)] mutation associated with the absence of germ cells in seminiferous tubules of infertile patients, which might suggest an anti-apoptotic role of human NANOS1. In this study, we aimed to determine a potential influence of human NANOS1 on the maintenance of TCam-2 model germ cells by investigating proliferation, cell cycle, and apoptosis. Constructs encoding wild-type or mutated human NANOS1 were used for transfection of TCam-2 cells, in order to investigate the effect of NANOS1 on cell proliferation, which was studied using a colorimetric assay, as well as apoptosis and the cell cycle, which were measured by flow cytometry. RNA-Seq (RNA sequencing) analysis followed by RT-qPCR (reverse transcription and quantitative polymerase chain reaction) was conducted for identifying pro-apoptotic genes repressed by NANOS1. Here, we show that overexpression of NANOS1 downregulates apoptosis in TCam-2 cells. Moreover, we found that NANOS1 represses a set of pro-apoptotic genes at the mRNA level. We also found that the infertility-associated p.[(Pro34Thr);(Ser83del)] mutation causes NANOS1 to functionally switch from being anti-apoptotic to pro-apoptotic in the human male germ cell line. Thus, this report is the first to show an anti-apoptotic role of NANOS1 exerted by negative regulation of mRNAs of pro-apoptotic genes.

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