Mitochondria play a fundamental role during development of the female germline. They are fragmented, round, and small. Despite these characteristics suggesting that they are inactive, there is accumulating evidence that mitochondrial dysfunctions are a major cause of infertility and generation of aneuploidies in humans. In addition, mitochondria and their own genomes (mitochondrial DNA-mtDNA) may become damaged with time, which might be one reason why aging leads to infertility. As a result, mitochondria have been proposed as an important target for evaluating oocyte and embryo quality, and developing treatments for female infertility. On the other hand, mutations in mtDNA may cause mitochondrial dysfunctions, leading to severe diseases that affect 1 in 4,300 people. Moreover, very low levels of mutated mtDNA seem to be present in every person worldwide. These may increase with time and associate with late-onset degenerative diseases such as Parkinson disease, Alzheimer disease, and common cancers. Mutations in mtDNA are transmitted down the maternal lineage, following a poorly understood pattern of inheritance. Recent findings have indicated existence in the female germline of a purifying filter against deleterious mtDNA variants. Although the underlying mechanism of this filter is largely unknown, it has been suggested to rely on autophagic degradation of dysfunctional mitochondria or selective replication/transmission of non-deleterious variants. Thus, understanding the mechanisms regulating mitochondrial inheritance is important both to improve diagnosis and develop therapeutic tools for preventing transmission of mtDNA-encoded diseases.

Oocyte mitochondria are increased in number, smaller, and rounder in appearance than mitochondria in somatic cells. Moreover, mitochondrial numbers and activity are narrowly tied with oocyte quality because of the key role of mitochondria to oocyte maturation. During oocyte maturation, mitochondria display great mobility and cluster at specific sites to meet the high energy demand. Conversely, oocyte mitochondria are not required during early oogenesis as coupling with granulosa cells is sufficient to support gamete's needs. In part, this might be explained by the importance of protecting mitochondria from oxidative damage that result in mutations in mitochondrial DNA (mtDNA). Considering mitochondria are transmitted exclusively by the mother, oocytes with mtDNA mutations may lead to diseases in offspring. Thus, to counterbalance mutation expansion, the oocyte has developed specific mechanisms to filter out deleterious mtDNA molecules. Herein, we discuss the role of mitochondria on oocyte developmental potential and recent evidence supporting a purifying filter against deleterious mtDNA mutations in oocytes.

Mitochondrial function, largely regulated by the dynamics of this organelle, is inextricably linked to the oocyte health. In comparison with most somatic cells, mitochondria in oocytes are smaller and rounder in appearance, suggesting limited fusion. The functional implications of this distinct morphology, and how changes in the mitochondrial shape translate to mitochondrial function in oogenesis is little understood. We, therefore, asked whether the pro‐fusion proteins mitofusins 1 (MFN1) and 2 (MFN2) are required for the oocyte development. Here we show that oocyte‐specific deletion of Mfn1, but not Mfn2, prevents the oocyte growth and ovulation due to a block in folliculogenesis. We pinpoint the loss of oocyte growth and ovulation to impaired PI3K‐Akt signaling and disrupted oocyte‐somatic cell communication. In support, the double loss of Mfn1 and Mfn2 partially rescues the impaired PI3K‐Akt signaling and defects in oocyte development secondary to the single loss of Mfn1. Together, this work demonstrates that the mitochondrial function influences the cellular signaling during the oocyte development, and highlights the importance of distinct, nonredundant roles of MFN1 and MFN2 in oogenesis.

1 Mitofusin 1 is required for the oocyte-granulosa cell communication that 1 regulates oogenesis 2 3 Thiago S SUMMARY 21Mitochondrial function, largely regulated by the dynamics of this organelle, is 22 inextricably linked to oocyte health. While the proteins that modulate 23 mitochondrial fusion, Mitofusin 1 (MFN1) and 2 (MFN2), are required for 24 embryogenesis, their role in oocyte development remains unclear. Here we 25show that the oocyte-specific deletion of Mfn1, but not Mfn2, results in a 26 complete loss of oocyte growth and ovulation due to a block in folliculogenesis 27 at the preantral-to-antral follicle transition. We pinpoint the loss of oocyte 28 ovulation to disrupted oocyte-somatic cell communication -Mfn1-null oocytes 29 are deficient for the production of the important somatic cell signaling factor 30 GDF9. Unexpectedly, the double loss of Mfn1 and Mfn2 mitigates the effects 31 on oocyte growth and ovulation, which is explained by a partial rescue of 32 oocyte-somatic cell communication and folliculogenesis. Together, this work 33 demonstrates that mitochondrial function influences communication of oocyte 34 with follicular somatic cells and suggests that the balanced expression of 35 modulators of mitochondrial dynamics is critical for proper oocyte development. 36Keywords: folliculogenesis, oocyte, mitochondria, mtDNA, fusion, mitofusin, 37 MFN1, MFN2, GDF9. 38 the rate of first polar body (PB1) extrusion, a readout for meiotic progression 130 to the metaphase-II stage. Only 3.1% of the oocytes that were ovulated by 131Mfn1&2-cKO mice contained PB1 ( Figure 1D), while 61.4% of them were 132 arrested at the GV stage. This finding was confirmed by in vitro maturation of 133 GV oocytes ( Figures 1E and 1F), indicating that Mfn1&2-cKO females were 134 infertile due to ovulation of unviable oocytes. Mating of superovulated 135Mfn1&2-cKO females with WT males also confirmed this as the ovulated 136 oocytes were not fertilized (data not show). The consequence of Mfn1 137

Some organizations in the Brazilian forestry sector, especially in the activities carried out in forest stands, do not follow the development pace of other industries and the adoption rate of management and quality methodologies and tools. This study aimed to evaluate the predictability of timber harvesting process based on critical points identified in the selective thinning and clear cut operations. Interviews and Pareto chart were used, for the identification and evaluation of the critical points, respectively, and for the evaluation of the process, it was used the Statistical Process Control (SPC) by attributes and variables in the main failures. In the interviews conducted with workers, seven critical points were identified. The evaluation with Pareto chart showed that 80% of the failures identified during harvest are attributed to the damage to the remaining trees, sorting (measures of length and diameter of the product) and stump height. Among the possible causes of the critical points are problems with employees’ training, regular maintenance of machinery and operations planning. In the evaluation with the CEP, the control charts indicated that the sorting and stump height, although within the limits specified by the company, was considered unstable and unpredictable