Activin A inhibits activation of human primordial follicles in vitro

Ding, Chi Christina; Thong, K.J.; Krishna, A; Telfer, Evelyn E.

doi:10.1007/s10815-010-9395-6

Cited by 30 publications

(28 citation statements)

References 40 publications

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“…The authors suggest that activin may play an inhibitory role in the recruitment and activation of primordial follicles in humans. However, in our analyses of ActA action, primordial follicles were neither stimulated nor inhibited in these processes using the same concentration of activin as reported by Ding et al (2010). Our analyses revealed that FSH decreased apoptosis occurring in vitro in the primordial follicle pool (14 vs 38%), supporting our Table 1 Proportion of follicle class represented as a percentage of total follicle numbers from day 4 fresh ovaries (before 10 days of culture) and all treatment groups (after 10 days of culture).…”

Section: Discussionmentioning

confidence: 67%

“…However, when compared with day 4 fresh ovaries, there was a significant decrease in primordial follicle number (P!0.001) consistent with follicle activation in vitro. Studies by Ding et al (2010) showed that ActA had a dose-dependent inhibitory effect on the activation of human primordial follicles in vitro. The authors suggest that activin may play an inhibitory role in the recruitment and activation of primordial follicles in humans.…”

Section: Discussionmentioning

confidence: 99%

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The effects of FSH and activin A on follicle development in vitro

Cossigny¹,

Findlay

Drummond

2012

Reproduction

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Numerous studies have reported on the roles of activins in gonadal regulation; however, little is known about their specific roles in early folliculogenesis. Ovarian follicular growth was investigated in 10-day cultures of day 4 postnatal whole ovaries treated with activin A (ActA; 50 ng/ml), with or without FSH (100 ng/ml) in vitro. We hypothesized that treatment with ActAGFSH would affect rates of growth and atresia in follicles. None of the treatments affected primordial follicle activation, and antral follicles were not observed after 10 days in culture. Primordial follicle numbers from all treatment groups were w20% of those in day 4 fresh ovaries, indicating that activation had occurred. In the presence of ActA, preantral follicle numbers increased significantly (P!0.0001). ActA alone decreased the proportion of atretic follicles in the primary and preantral classes, whereas the combined treatment of ActACFSH increased the proportion of atretic preantral oocytes. Real-time PCR analysis revealed that follistatin, FSH receptor, and activin bA and bB subunits were all expressed at significantly higher levels in the ActA-only treated group but not in the ActACFSH group. Here, we report novel findings supporting the role of FSH in primordial follicle survival through an action on apoptosis and a stimulatory role of ActA in the primordial to primary and preantral stages of follicle development, suggesting an inhibitory action of activin on oocyte apoptosis.

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Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

The effects of FSH and activin A on follicle development in vitro

Cossigny¹,

Findlay

Drummond

2012

Reproduction

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“…Over the last decade, studies using mouse genetic models, in vivo injection, and ex vivo organ culture approaches have demonstrated that many TGF-b superfamily and signaling proteins mediate the early stages of folliculogenesis. These studies have indicated that several key family members, including AMH, activin, inhibin, BMP-4, and BMP-7, are important for the primordial to primary follicle transition [31][32][33][34] and that Smad proteins are essential for primordial germ cell development and folliculogenesis [35]. In accord with these findings showing that the TGF-b signaling pathway is critical for primordial FIG.…”

Section: Mirnas Regulate Early Follicle Developmentmentioning

confidence: 85%

Expression Patterns and Regulatory Functions of MicroRNAs During the Initiation of Primordial Follicle Development in the Neonatal Mouse Ovary1

Yang

Wang

Luo

et al. 2013

Biology of Reproduction

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The initiation of primordial follicle development is essential for female fertility, but the signals that trigger this process are poorly understood. Given the potentially important roles of microRNAs (miRNAs) in the ovary, we aimed to study the expression patterns and regulatory functions of miRNAs during the initiation of primordial follicle development. Expression patterns of miRNA in the neonatal mouse ovary were profiled by microarray, and 24 miRNAs whose abundances differed significantly between ovaries from 3- and 5-day-old mice were identified. Pathway enrichment analysis revealed that 48 signal transduction pathways are modulated by the up-regulated miRNAs and 29 pathways are modulated by the down-regulated miRNAs (P-value and false discovery rate < 0.001). A miRNA-mRNA regulatory network was established for TGF-beta signaling pathway-related genes. Among the miRNAs involved in this pathway, miR-145 was chosen for further analysis. Down-regulation of miR-145 using an antagomir (AT) decreased the proportion and number of the primordial follicles and increased that of the growing follicles in the cultured ovaries (P < 0.05). The mean oocyte diameter in the primordial follicles was significantly greater in the AT group relative to the AT-negative control group (P < 0.05), whereas the mean oocyte diameter in growing follicles was smaller in the AT group than in the AT-negative control group. In addition, we confirmed that miR-145 targets Tgfbr2. The miR-145 AT caused an increase in TGFBR2 expression and activation of Smad signaling but did not affect the p38 MAPK or JNK pathway. These data suggest that miRNAs and the signaling pathways they modulate are involved in the initiation of primordial follicle development, and miR-145 targets Tgfbr2 to regulate the initiation of primordial follicle development and maintain primordial follicle quiescence.

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“…In vitro culture experiments were conducted using thawed ovarian samples from 5 patients, presenting the higher number of follicles according to the previous histological examination. As shown in previous studies, culture of ovarian pieces allows cellular interactions between follicles and surrounding stroma indispensable to sustain follicular growth initiation [8,25,34]. In order to retain the 3D structure of the follicles, a low-attachment culture system limiting stroma cell adhesion on the culture support was used.…”

Section: Discussionmentioning

confidence: 99%

Quality and functionality of human ovarian tissue after cryopreservation using an original slow freezing procedure

Sanfilippo

Canis

Romero

et al. 2012

J Assist Reprod Genet

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Purpose To evaluate the efficiency of an original slow freezing protocol on the quality and function of human ovarian cortex. Methods Human ovarian tissues were cryopreserved using a freezing medium supplemented with propanediol and raffinose as cryoprotectants and antioxidants (L-glutamine, taurine). Samples were then frozen using a faster cooling rate than the usual one. Viability and morphology of follicles, DNA fragmentation in follicles and stroma as well as histology of the vascular endothelium were analyzed before and after freezing/thawing. Moreover, a functional analysis was performed based on the evaluation of follicular growth and development in thawed ovarian tissues that were cultured in vitro. Results Our freezing/thawing protocol allows preservation of a high proportion of viable follicles and the preservation of the different follicle developmental stages (p>0.05 versus fresh control). 70.5±5.2 % of follicles retained an intact morphology after cryopreservation (p=0.04). Stroma cells but not follicles exhibited a slight increase of DNA fragmentation after thawing (p<0.05). Microvessel endothelium within thawed tissues appeared to be preserved. Granulosa cells showed signs of proliferation in follicles cultured for 12 days. Secretion of 17β-oestradiol significantly increased during in vitro culture. Conclusions This protocol leads to good preservation of ovarian integrity and functionality post-thawing and thus appears as a suitable technique of ovarian tissue cryopreservation in clinical settings. Further research could be extended to optimize conditions of in vitro culture.

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Activin A inhibits activation of human primordial follicles in vitro

Cited by 30 publications

References 40 publications

The effects of FSH and activin A on follicle development in vitro

The effects of FSH and activin A on follicle development in vitro

Expression Patterns and Regulatory Functions of MicroRNAs During the Initiation of Primordial Follicle Development in the Neonatal Mouse Ovary1

Quality and functionality of human ovarian tissue after cryopreservation using an original slow freezing procedure

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