Bioengineering the Ovarian Follicle Microenvironment

Shea, Lonnie D.; Woodruff, Teresa K.; Shikanov, Ariella

doi:10.1146/annurev-bioeng-071813-105131

Cited by 145 publications

(103 citation statements)

References 126 publications

(152 reference statements)

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“…The most probable explanation of the lowest PCNA expression in the granulosa cells of the fresh control might be that the ovary contains mainly primordial follicles (Shea et al, 2014), in which occasionally PCNA-positive cells have been found (Silva et al, 2004). Hemamalini et al (2003) have shown that EGF (50 ng/mL) is a mitogenic factor promoting ovine granulosa cell proliferation and improvement of DNA synthesis.…”

Section: Discussionmentioning

confidence: 99%

Blocking the PI3K pathway or the presence of high concentrations of EGF inhibits the spontaneous activation of ovine primordial follicles in vitro

Santos¹,

Santos²,

Menezes³

et al. 2017

Anim Reprod

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The aims of this study were to verify the effects of Epidermal Growth Factor (EGF) on the morphology, primordial follicle activation, growth and proliferation of granulosa cells of ovine follicles cultured in situ, as well as the effect of a PI3K inhibitor on the follicular activation. Ten ovine ovaries were divided into fragments, being one fixed for histological analysis (fresh control). The remaining fragments were cultured for 7 days in control medium (α-MEM + ) alone or supplemented with EGF (1, 10, 50, 100 or 200 ng/mL). Follicles were classified as normal or atretic, as primordial or growing, and the oocyte and follicle diameters were measured. PCNA immunohistochemistry was performed in the fresh control and in treatment that showed the best results for follicular activation. Pharmacologic inhibition of PI3K activity was performed through pretreatment in media added with 50 µM LY294002 for 1 h. The percentage of normal follicles decreased (P < 0.05) after 7 days of culture in all treatments compared to the fresh control. A significant reduction in the percentage of primordial follicles and an increase (P < 0.05) in the growing ones were observed in all treatments compared to fresh control. Furthermore, both the control medium and 1 ng/mL EGF promoted an increase (P < 0.05) in follicular activation compared to other EGF treatments. The PCNA-positive cells in the EGF treatment were higher (P < 0.05) than in fresh control and α-MEM + . Pretreatment of ovarian tissue with PI3K inhibitor significantly inhibited (P < 0.05) α-MEM + -stimulated primordial follicle activation, but had no effect on EGF-stimulated activation (P > 0.05). In conclusion, PI3K pathway mediates the in vitro spontaneous activation of sheep primordial follicles. Moreover, EGF may act indirectly on follicular activation by promoting granulosa cell proliferation at 1 ng/mL, and EGF inhibited follicle activation in concentrations similar or higher than 10 ng/mL.

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Section: Discussionmentioning

confidence: 99%

Blocking the PI3K pathway or the presence of high concentrations of EGF inhibits the spontaneous activation of ovine primordial follicles in vitro

Santos¹,

Santos²,

Menezes³

et al. 2017

Anim Reprod

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“…For fertility aid, ovarian- and follicle-related bioengineering applications have particularly been explored as means to cure infertility caused by conventional anti-cancer treatments 89. Fertility is particularly challenging to retain in leukemia-treated females where the otherwise successful method of re-transplanting cryopreserved ovarian tissue is unsafe due to the risk of reintroducing malignant cells 30…”

Section: Introductionmentioning

confidence: 99%

Uterine Tissue Engineering and the Future of Uterus Transplantation

2016

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The recent successful births following live donor uterus transplantation are proof-of-concept that absolute uterine factor infertility is a treatable condition which affects several hundred thousand infertile women world-wide due to a dysfunctional uterus. This strategy also provides an alternative to gestational surrogate motherhood which is not practiced in most countries due to ethical, religious or legal reasons. The live donor surgery involved in uterus transplantation takes more than 10 h and is then followed by years of immunosuppressive medication to prevent uterine rejection. Immunosuppression is associated with significant adverse side effects, including nephrotoxicity, increased risk of serious infections, and diabetes. Thus, the development of alternative approaches to treat absolute uterine factor infertility would be desirable. This review discusses tissue engineering principles in general, but also details strategies on how to create a bioengineered uterus that could be used for transplantation, without risky donor surgery and any need for immunosuppression. We discuss scaffolds derived from decellularized organs/tissues which may be recellularized using various types of autologous somatic/stem cells, in particular for uterine tissue engineering. It further highlights the hurdles that lay ahead in developing an alternative to an allogeneic source for uterus transplantation.

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“…In strategy three, oophropexy and pelvic shielding do not provide ovarian protection when chemotherapy is used, while GnRH analogs do not provide ovarian protection when radiotherapy is used [31, 32, 33, 34]. In order to avoid such different contraindications, new advances in research to restore fertility of female cancer patients have been recently attempted including artificial ovary [35, 36, 37, 38], and use of mesenchymal stem cells [39, 40, 41]. …”

Section: Expert Commentarymentioning

confidence: 99%

Anticancer treatments and female fertility: clinical concerns and role of oncologists in oncofertility practice

Salama

Woodruff

2017

Expert Review of Anticancer Therapy

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Introduction: Anticancer treatments such as aggressive chemotherapy and radiotherapy have deleterious gonadotoxic side effects and are considered the most common causes of pathological and iatrogenic fertility loss in women. Areas Covered: In order to preserve fertility of young women and girls with cancer, several established, experimental, and debatable options can be offered in the emerging field of oncofertility. This article reviews the effects of anticancer treatments on female fertility and discusses the current challenges and future directions of fertility preservation options that can be offered to the female patients with cancer. Expert Commentary: Although promising, several medical, economic, social and legal barriers face oncofertility practice around the globe especially in underserved areas. To overcome such barriers, more effective solutions should be provided to spread awareness and enhance communication between patients, oncologists and gynecologists. Early referral by oncologists before initiation of chemotherapy and radiotherapy is an important key factor for success in female fertility preservation strategies.

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Bioengineering the Ovarian Follicle Microenvironment

Cited by 145 publications

References 126 publications

Blocking the PI3K pathway or the presence of high concentrations of EGF inhibits the spontaneous activation of ovine primordial follicles in vitro

Blocking the PI3K pathway or the presence of high concentrations of EGF inhibits the spontaneous activation of ovine primordial follicles in vitro

Uterine Tissue Engineering and the Future of Uterus Transplantation

Anticancer treatments and female fertility: clinical concerns and role of oncologists in oncofertility practice

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