The stromal fibrosis in aging ovary

Umehara, Takashi; Richards, JoAnne S.; Shimada, Masayuki

doi:10.18632/aging.101370

Cited by 14 publications

(11 citation statements)

References 7 publications

(7 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We assume that the balance between activation of dormant follicles and atresia of growing follicles may be important to maintain ovarian reserve in grafted ovarian tissue. In mouse study, aged ovaries showed fibrosis and growth arrest at secondary stage, 29 which is contrary to our present study. As we mentioned formerly, ovarian fibrosis is associated with varieties of dysregulations of folliculogenesis.…”

Section: Discussioncontrasting

confidence: 99%

Accumulation of fibrosis and altered perifollicular stromal differentiation in vitrified‐thawed human ovarian tissue xenografted to nude mice.

Kitajima

Murakami

Kitajima

et al. 2022

Reprod Medicine & Biology

View full text Add to dashboard Buy / Rent full text

Purpose Ovarian tissue cryopreservation and its auto‐transplantation is promising technique in fertility preservation. Longevity of grafted tissue is limited though mechanism of follicle reduction is not fully understood. We evaluated histological alteration of vitrified‐thawed ovarian tissue that grafted to nude mice. Materials and Methods Human ovarian tissue was cryopreserved by vitrification. After thawing, they were grafted to mesentery of nude mice. Twelve weeks after transplantation, the implants were removed and histologically examined. The presence of follicles, the degree of fibrosis, and TUNEL staining in surrounding cortex were evaluated. The stromal expressions of alpha‐smooth muscle actin (aSMA) were determined. Results Normal ovarian cortex was decreased, and fibrotic area were significantly increased after grafting. The distributions of developmental stage of follicles shifted toward activation of follicular growth. Stromal TUNEL staining was increased in frozen/thawed tissue. The expression of aSMA were found in perifollicular stroma of growing follicles, which were decreased in grafted tissue associated with reduction of cortical stroma. Conclusions Fibrosis, reduced cortical stroma, and activation of dormant follicles were concomitantly observed in grafted ovarian cortex, which may relate to limited longevity. Perifollicular aSMA expression can be regarded as a marker of the competence of cortical stroma that regulate follicular development.

show abstract

Section: Discussioncontrasting

confidence: 99%

Accumulation of fibrosis and altered perifollicular stromal differentiation in vitrified‐thawed human ovarian tissue xenografted to nude mice.

Kitajima

Murakami

Kitajima

et al. 2022

Reprod Medicine & Biology

View full text Add to dashboard Buy / Rent full text

show abstract

“…Our study revealed that the local mechanical stress inducing nuclear rotation is a crucial clue to the local environment. This may provide an explanation for the clinical observation that fibrosis in the ovaries increases with age ( 38 , 39 ), which generally makes it difficult to produce mature oocytes.…”

Section: Discussionmentioning

confidence: 95%

Mechanical stress accompanied with nuclear rotation is involved in the dormant state of mouse oocytes

et al. 2019

View full text Add to dashboard Buy / Rent full text

The most immature oocytes remain dormant in primordial follicles in the ovary, ensuring the longevity of female reproductive life. Despite its biological and clinical importance, knowledge of mechanisms regulating the dormant state remains limited. Here, we show that mechanical stress plays a key role in maintaining the dormant state of the oocytes in primordial follicles in mice. Transcriptional and histological analyses revealed that oocytes were compressed by surrounding granulosa cells with extracellular matrix. This environmental state is functionally crucial, as oocytes became activated upon loosening the structure and the dormancy was restored by additional compression with exogenous pressure. The nuclei of oocytes in primordial follicles rotated in response to the mechanical stress. Pausing the rotation triggered activation of oocytes through nuclear export of forkhead box O3 (FOXO3). These results provide insights into the mechanisms by which oocytes are kept dormant to sustain female reproductive life.

show abstract

“…In some mouse strains, this inflammation is accompanied by fibrosis characterized by increased collagen I and III levels in mice of advanced reproductive age [ 15 ]. Fibrosis and additional changes in the extracellular matrix are also conserved in the aging human ovary, demonstrating the translational relevance of this aging phenomenon [ 16 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Fibroinflammatory Signatures Increase with Age in the Human Ovary and Follicular Fluid

Machlin

Barishansky

Kelsh

et al. 2021

IJMS

View full text Add to dashboard Buy / Rent full text

The female reproductive system ages before any other organ system in the body. This phenomenon can have tangible clinical implications leading to infertility, miscarriages, birth defects and systemic deterioration due to estrogen loss. “Fibroinflammation” is a hallmark of aging tissues; there is an increase in inflammatory cytokines and fibrotic tissue in the aging ovarian stroma. We systematically evaluated immunomodulatory factors in human follicular fluid, which, like the stroma, is a critical ovarian microenvironment directly influencing the oocyte. Using a cytokine antibody array, we identified a unique fibroinflammatory cytokine signature in follicular fluid across an aging series of women (27.7–44.8 years). This signature (IL-3, IL-7, IL-15, TGFβ1, TGFβ3 and MIP-1) increased with chronologic age, was inversely correlated to anti-Müllerian hormone (AMH) levels, and was independent of body mass index (BMI). We focused on one specific protein, TGFβ3, for further validation. By investigating this cytokine in human cumulus cells and ovarian tissue, we found that the age-dependent increase in TGFβ3 expression was unique to the ovarian stroma but not other ovarian sub-compartments. This study broadens our understanding of inflammaging in the female reproductive system and provides a defined fibroinflammatory aging signature in follicular fluid and molecular targets in the ovary with potential clinical utility.

show abstract

The stromal fibrosis in aging ovary

Cited by 14 publications

References 7 publications

Accumulation of fibrosis and altered perifollicular stromal differentiation in vitrified‐thawed human ovarian tissue xenografted to nude mice.

Accumulation of fibrosis and altered perifollicular stromal differentiation in vitrified‐thawed human ovarian tissue xenografted to nude mice.

Mechanical stress accompanied with nuclear rotation is involved in the dormant state of mouse oocytes

Fibroinflammatory Signatures Increase with Age in the Human Ovary and Follicular Fluid

Contact Info

Product

Resources

About