Aspects of Ovarian Follicle Development throughout Life

Macklon, Nick S.; Fauser, Bart C.J.M.

doi:10.1159/000023456

Cited by 68 publications

(74 citation statements)

References 31 publications

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“…2A); cotreatment of bpV(pic) plus 740Y-P showed most pronounced increases based on ovarian weight determination This article is a PNAS Direct Submission. 1 To whom correspondence should be addressed. E-mail: aaron.hsueh@stanford.edu.…”

Section: Resultsmentioning

confidence: 99%

Activation of dormant ovarian follicles to generate mature eggs

Kawamura

Cheng

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

379

340

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Although multiple follicles are present in mammalian ovaries, most of them remain dormant for years or decades. During reproductive life, some follicles are activated for development. Genetically modified mouse models with oocyte-specific deletion of genes in the PTEN-PI3K-Akt-Foxo3 pathway exhibited premature activation of all dormant follicles. Using an inhibitor of the Phosphatase with TENsin homology deleted in chromosome 10 (PTEN) phosphatase and a PI3K activating peptide, we found that short-term treatment of neonatal mouse ovaries increased nuclear exclusion of Foxo3 in primordial oocytes. After transplantation under kidney capsules of ovariectomized hosts, treated follicles developed to the preovulatory stage with mature eggs displaying normal epigenetic changes of imprinted genes. After in vitro fertilization and embryo transfer, healthy progeny with proven fertility were delivered. Human ovarian cortical fragments from cancer patients were also treated with the PTEN inhibitor. After xeno-transplantation to immune-deficient mice for 6 months, primordial follicles developed to the preovulatory stage with oocytes capable of undergoing nuclear maturation. Major differences between male and female mammals are unlimited number of sperm and paucity of mature oocytes. Thus, short-term in vitro activation of dormant ovarian follicles after stimulation of the PI3K-Akt pathway allows the generation of a large supply of mature female germ cells for future treatment of infertile women with a diminishing ovarian reserve and for cancer patients with cryo-preserved ovaries. Generation of a large number of human oocytes also facilitates future derivation of embryonic stem cells for regenerative medicine.

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Section: Resultsmentioning

confidence: 99%

Activation of dormant ovarian follicles to generate mature eggs

Kawamura

Cheng

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

379

340

View full text Add to dashboard Cite

show abstract

“…Previous studies have shown that primordial follicle depletion is the fundamental reason for physiological and pathological ovarian aging in mammalian females [1]. Historically, it was believed that the majority of the primordial follicle pool remains in a dormant state and declines with age under physiological conditions [2].…”

Section: Introductionmentioning

confidence: 99%

Ovarian Germline Stem Cells (OGSCs) and the Hippo Signaling Pathway Association with Physiological and Pathological Ovarian Aging in Mice

Zhou

Zheng

et al. 2015

Cell Physiol Biochem

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Background: The Hippo signaling pathway plays fundamental roles in stem cell maintenance in a variety of tissues and has thus implications for stem cell biology. Key components of this recently discovered pathway have been shown to be associated with primordial follicle activation. However, whether the Hippo signaling pathway plays a role in the development of Ovarian Germline Stem Cells (OGSCs) during physiological and pathological ovarian aging in mice is unknown. Methods: Mice at the age of 7 days (7D), or of 2, 10, or 20 months (2M, 10M, 20M) and mice at 2M treated with TPT and CY/BUS drugs were selected as physiological and pathological ovarian aging models, respectively. Immunohistochemistry was used to assess the development of follicles, and the co-localization of genes characteristic of OGSCs with MST1, LATS2 and YAP1 was assessed by immunofluorescence, western blotting and real-time PCR methods. Results: The Hippo signal pathway and MVH/OCT4 genes were co-expressed in the mouse ovarian cortex. The level and co-localization of LATS2, MST1, MVH, and OCT4 were significantly decreased with increased age, but YAP1 was more prevalent in the mouse ovarian cortex of 2M mice than 7D mice and was not observed in 20M mice. Furthermore, YAP1, MVH, and OCT4 were gradually decreased after TPT and CY/BUS treatment, and LATS2 mRNA and protein up-regulation persisted in TPT- and CY/BUS-treated mice. However, the expression of MST1 was lower in the TPT and CY/BUS groups compared with the control group. In addition, pYAP1 protein showed the highest expression in the ovarian cortexes of 7D mice compared with 20M mice, and the value of pYAP1/YAP1 decreased from 7D to 20M. Moreover, pYAP1 decreased in the TPT- and CY/BUS-treated groups, but the value of pYAP1/YAP1 increased in these groups. Conclusion: Taken together, our results show that the Hippo signaling pathway is associated with the changes that take place in OGSCs during physiological and pathological ovarian aging in mice. Thus, the Hippo signaling pathway may be involved in the development schedule of OGSCs.

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“…LBW, Hypergonadotropinemia, Small Uterine and Ovarian Size, and Central Adiposity Prenatal life is a critical window in the development of the female external genitalia [17] . In postnatal life, the human gonadotropic axis has two phases of high activity: one in infancy and another starting in puberty and persisting into adulthood.…”

Section: Introductionmentioning

confidence: 99%

Endocrinology and Gynecology of Girls and Women with Low Birth Weight

Ibáñez

López‐Bermejo²,

Díaz³

et al. 2011

Fetal Diagn Ther

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In girls, low birth weight (LBW), when followed by postnatal catch-up growth, is accompanied by endocrine-metabolic abnormalities which include a more adipose body composition (with increased visceral fat), insulin resistance and a less favorable adipokine profile as early as in the pre-school age. These girls also exhibit follicle-stimulating hormone hypersecretion both in early infancy and early post-menarche, with reduced uterine and ovarian size in adolescence. These endocrine and gynecological changes result in a decreased ovulation rate and in an advanced tempo of adrenarche, pubertal development and menarche (by nearly a year, compared to non-LBW girls). The earlier maturation in LBW girls may result in a loss of about 1 SD in height, as compared with target height. During the post-menarcheal period, LBW girls are at increased risk of developing polycystic ovary syndrome. Early insulin sensitization may prevent or delay some of the endocrine-metabolic abnormalities associated to LBW.

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Aspects of Ovarian Follicle Development throughout Life

Cited by 68 publications

References 31 publications

Activation of dormant ovarian follicles to generate mature eggs

Activation of dormant ovarian follicles to generate mature eggs

Ovarian Germline Stem Cells (OGSCs) and the Hippo Signaling Pathway Association with Physiological and Pathological Ovarian Aging in Mice

Endocrinology and Gynecology of Girls and Women with Low Birth Weight

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