Molecular Basis Associated with the Control of Primordial Follicle Activation During Transplantation of Cryopreserved Ovarian Tissue

Terren, Carmen; Munaut, Carine

doi:10.1007/s43032-020-00318-z

Cited by 10 publications

(12 citation statements)

References 80 publications

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“…Furthermore, this study presents a granulosa cell-focused investigation of primordial follicle activation in mice. Previous mouse model studies using bulk RNA-seq to capture primordial follicle activation or early ovarian time points analyze a compendium of cell types and do not focus specifically on the granulosa cell to granulosa cell transition [ 48 , 49 ]. Single cell sequencing has, so far, been underutilized in the study of primordial follicle activation and lacking depth in the analysis of granulosa cells during this important physiological event [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic profiling of neonatal mouse granulosa cells reveals new insights into primordial follicle activation

Ford

Frost

Beckett

et al. 2021

Biology of Reproduction

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The dormant population of ovarian primordial follicles is determined at birth and serves as the reservoir for future female fertility. Yet our understanding of the molecular, biochemical, and cellular processes underpinning primordial follicle activation remains limited. The survival of primordial follicles relies on the correct complement and morphology of granulosa cells, which provide signalling factors essential for oocyte and follicular survival. To investigate the contribution of granulosa cells in the primordial-to-primary follicle transition, gene expression profiles of granulosa cells undergoing early differentiation were assessed in a murine model. Ovaries from C57Bl/6 mice were enzymatically dissociated at time-points spanning the initial wave of primordial follicle activation. Post-natal day (PND) 1 ovaries yielded primordial granulosa cells, and PND4 ovaries yielded a mixed population of primordial and primary granulosa cells. The comparative transcriptome of granulosa cells at these time-points was generated via Illumina NextSeq 500 system which identified 131 significantly differentially expressed transcripts. The differential expression of eight of the transcripts was confirmed by RT-qPCR Following biological network mapping via Ingenuity Pathway Analysis, the functional expression of the protein products of three of the differentially expressed genes, namely FRZB, POD1 and ZFX, was investigated with in-situ immunolocalisation in PND4 mouse ovaries was investigated. Finally, evidence was provided that Wnt pathway antagonist, secreted frizzled-related protein 3 (FRZB), interacts with a suppressor of primordial follicle activation WNT3A and may be involved in promoting primordial follicle activation. This study highlights the dynamic changes in gene expression of granulosa cells during primordial follicle activation and provides evidence for a renewed focus into the Wnt signalling pathway’s role in primordial follicle activation.

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Section: Discussionmentioning

confidence: 99%

Transcriptomic profiling of neonatal mouse granulosa cells reveals new insights into primordial follicle activation

Ford

Frost

Beckett

et al. 2021

Biology of Reproduction

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“…For functionality preservation, both the technique and the graft sizes are important. The actual recommendations are to slow freeze and fast unfreeze small ovarian tissue slices, either (8-10) mm× 5 mm or 2 mm × 2 mm [9,74]. This procedure has its limitations, such as the low quality of the ovarian tissue but also relapses of cancer after introducing the graft in the ovarian area, especially when the initial recommendation was acute leukemia [75,76].…”

Section: Fertility Preservation Before Cancer Treatmentmentioning

confidence: 99%

“…The decrease in serum FSH and increased estradiol confirm this. Regarding conception following the procedure, the positive result with pregnancies rises up to 50% after spontaneous menstruation onset [74]. When reintroducing graft is not an option, an artificial ovary may represent an alternative solution [77].…”

Section: Fertility Preservation Before Cancer Treatmentmentioning

confidence: 99%

“…The common ovarian biomarkers, such as FSH, estradiol, AMH, and ultrasound follicle count (AFC), can only superficially orientate us regarding present ovarian function [95]. Age is probably one of the most important factors in terms of future fertility because the younger the patient, the higher the number and quality of the remaining oocyte [74]. It is also important the moment of evaluation for both paracrine biomarkers and ultrasound findings.…”

Section: Fertility Preservation After Cancer Treatmentmentioning

confidence: 99%

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A Warning Call for Fertility Preservation Methods for Women Undergoing Gonadotoxic Cancer Treatment

et al. 2021

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Malignant hematological conditions have recognized an increased incidence and require aggressive treatments. Targeted chemotherapy, accompanied or not by radiotherapy, raises the chance of defeating the disease, yet cancer protocols often associate long-term gonadal consequences, for instance, diminished or damaged ovarian reserve. The negative effect is directly proportional to the types, doses, time of administration of chemotherapy, and irradiation. Additionally, follicle damage depends on characteristics of the disease and patient, such as age, concomitant diseases, previous gynecological conditions, and ovarian reserve. Patients should be adequately informed when proceeding to gonadotoxic therapies; hence, fertility preservation should be eventually regarded as a first-intention procedure. This procedure is most beneficial when performed before the onset of cancer treatment, with the recommendation for embryos or oocytes’ cryopreservation. If not feasible or acceptable, several options can be available during or after the cancer treatment. Although not approved by medical practice, promising results after in vitro studies increase the chances of future patients to protect their fertility. This review aims to emphasize the mechanism of action and impact of chemotherapy, especially the one proven to be gonadotoxic, upon ovarian reserve and future fertility. Reduced fertility or infertility, as long-term consequences of chemotherapy and, particularly, following bone marrow transplantation, is often associated with a negative impact of recovery, social and personal life, as well as highly decreased quality of life.

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“…As the basic functional unit of the ovary, the primordial follicle is a critical subject for studies related to ovarian physiology and pathogenesis [4][5][6]. The measurement of PFP is accomplished based on microscopic recognition and individual counting by the visual observation of researchers on serial tissue sections [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Sohlh1 and Lhx8 are prominent biomarkers to estimate the primordial follicle pool in mice

Liu

Wang

et al. 2022

Preprint

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Efficient evaluation of the primordial follicle pool (PFP) of mammalian models is an essential subject in biomedical research relating to ovarian physiology and pathogenesis. Our recent study has identified a gene signature including Sohlh1, Nobox, Lhx8, Tbpl2, Stk31, Padi6, and Vrtn strongly correlated with ovarian reserve by using bioinformatics analysis. Aimed to investigate the validity of these candidate biomarkers for evaluating the PFP, we utilized an OR comparison model to decode the relationship between the numbers of PFP and candidate biomarkers in the present study. Our results suggest that these biomarkers Sohlh1, Nobox, Lhx8, Tbpl2, Stk31, Padi6, and Vrtn possess independent potential to evaluate the number of the PFP. And the combination of Sohlh1and Lhx8 can be used as the optimal biomarkers for rapid assessment of the PFP in the murine ovary. Our findings provide a new perspective for evaluating the PFP of the ovary in animal studies and the clinic.

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Molecular Basis Associated with the Control of Primordial Follicle Activation During Transplantation of Cryopreserved Ovarian Tissue

Cited by 10 publications

References 80 publications

Transcriptomic profiling of neonatal mouse granulosa cells reveals new insights into primordial follicle activation

Transcriptomic profiling of neonatal mouse granulosa cells reveals new insights into primordial follicle activation

A Warning Call for Fertility Preservation Methods for Women Undergoing Gonadotoxic Cancer Treatment

Sohlh1 and Lhx8 are prominent biomarkers to estimate the primordial follicle pool in mice

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