Activin a stimulates meiotic maturation of human oocytes and modulates granulosa cell steroidogenesis in vitro

Alak, Baha M.; Coşkun, Serdar; Friedman, Chad I.; Kennard, Elizabeth A.; Kim, Moon H.; Seifer, David B.

doi:10.1016/s0015-0282(98)00386-0

Cited by 95 publications

(47 citation statements)

References 21 publications

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“…In vitro activin promotes and follistatin inhibits meiotic and cytoplasmic maturation of the oocytes (Alak et al, 1996(Alak et al, , 1998. Furthermore, activin potentiates the development of blastocysts from denuded or cumulusenclosed bovine oocytes, whereas follistatin neutralizes these actions (Silva and Knight, 1998).…”

Section: Interaction With Activinsmentioning

confidence: 99%

Regulation of ovarian function by the TGF-beta superfamily and follistatin

et al. 2003

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The role of follistatin as an activin-binding protein has dominated the study of this molecule for the last 10 years. However, there is emerging evidence that follistatin has a role in modulating the biology of other members of the transforming growth factor beta (TGF-beta) superfamily. This review summarizes the current concepts encompassing follistatin biochemistry as well as molecules with which it is functionally associated. Moreover, the importance of the two follistatin isoforms (follistatin-288 and follistatin-315) is discussed with particular emphasis on the regulation of the ovary. In addition to activin, this review discusses the functions of other members of the TGF-beta superfamily, for example growth differentiation factor 9 (GDF-9), bone morphogenetic protein 15 (BMP-15), BMP-6, BMP-4 and BMP-7, in the ovary, and the potential interactions between follistatin and these growth factors. The complex network of TGF-beta superfamily growth factor members involved in the modulation of ovarian function and the interactions of follistatin with these proteins is highlighted.

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Section: Interaction With Activinsmentioning

confidence: 99%

Regulation of ovarian function by the TGF-beta superfamily and follistatin

et al. 2003

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“…(Adapted from Hillier, 1991. ) 1996), rats (Sadatsuki et al, 1993) and humans (Alak et al, 1998), an effect that was inhibited by follistatin. Exposure of denuded or cumulus-enclosed bovine oocytes to activin-A did not affect cleavage rate after IVF but increased their developmental competence to form blastocysts (Silva and Knight, 1998).…”

Section: Paracrine Effects On the Oocytementioning

confidence: 99%

Potential local regulatory functions of inhibins, activins and follistatin in the ovary

Knight¹,

Glister²

2001

Reproduction

256

117

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The changing pattern of granulosa cell expression of inhibin/activin subunits and follistatin during follicle development and their differential regulation by extrinsic and intraovarian factors supports evidence from functional studies, mostly in vitro, that these proteins have important roles in folliculogenesis, oocyte maturation and corpus luteum function. Gonadal inhibins function as negative feedback hormones to regulate the synthesis and secretion of pituitary FSH, a key determinant of follicle development, but there is little supportive evidence for a peripheral endocrine role for ovary-derived activins or follistatin in this regard. However, activins and follistatin are expressed in numerous other tissues, including anterior pituitary, and they are firmly implicated as local intrapituitary regulators of FSH secretion. Intraovarian actions of granulosa cell-derived activins include the promotion of granulosa cell proliferation and upregulation of FSH receptors, P450arom, oestrogen synthesis, granulosa cell LH receptors and enhancement of oocyte maturation. Through its activin-binding role, follistatin can reverse each of these activin-induced responses. In addition to their endocrine feedback role, granulosa-derived inhibins can sensitize theca cells to LH, thereby enhancing the production of androgens, an essential requirement for follicular oestrogen synthesis. Activins can oppose this effect and suppress thecal androgen production. Granulosa cells overproduce inhibin a subunit precursor relative to betaA/betaB subunit precursors and evidence indicates that different parts of the inhibin a subunit precursor have intrinsic biological activities distinct from inhibin alphabetaA/B dimer, and serve as additional local modulators of follicle and corpus luteum function.

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“…Similar results have already been reported in bovine (Vantol et al, 1994;Izadyar et al, 1996) and porcine (Coskun and Lin, 1994) oocytes, suggesting no effect of activin-A on oocyte maturation. Considering that activin-A is able to directly stimulate FSH synthesis and secretion, promote the release of the GnRH, and also stimulate the increase of FSH and LH receptors in the granulosa cells (Alak et al, 1998;Norwitz et al, 2002), the ineffectiveness of exogenous activin-A may be either because of activin-A production by the COCs and/or the presence of FSH and LH in our culture medium. However, this does not exclude the possibility that activin-A, secreted by the granulosa cells and present in the follicular fluid, has an effect on the cytoplasmic maturation of goat oocytes, which would affect subsequent pre-implantation embryo development.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to being a local regulator of folliculogenesis, activin-A is able to directly stimulate FSH synthesis and secretion, and to promote the release of the gonadotrophin-releasing hormone (GnRH) (Childs and Unabia, 1997). Activin-A can also stimulate the increase of FSH and LH receptors in granulosa cells, and it plays a role in progesterone production (Alak et al, 1998;Tsuchiya et al, 1999). Thus, the granulosa cells are likely to be the main source of paracrine factors and are crucial for oocyte maturation.…”

Section: Introductionmentioning

confidence: 99%

“…However, none of these approaches have managed to improve developmental competence from prepubertal goat oocytes. Keeping in mind that protein and mRNA for activin-A and activin receptors have been localized in both oocyte and granulosa cells of follicles at various developmental stages in a variety of species including caprine (Silva et al, 2004 and, and the potential role of activin-A in the regulation of oocyte maturation has been demonstrated to promote in vitro oocyte maturation (IVM) in the rat (Itoh et al, 1990), cow (Stock et al, 1997), rhesus monkey (Alak et al, 1996) and human (Alak et al, 1998), we hypothesized that the addition of activin-A to the maturation and/or embryo culture medium could improve the in vitro potential of prepubertal goat oocytes for nuclear and cytoplasmic maturation and embryo development. Such a system could potentially provide an unlimited source of competent oocytes for biomedical application.…”

Section: Introductionmentioning

confidence: 99%

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In vitro developmental competence of prepubertal goat oocytes cultured with recombinant activin-A

Hammami

Izquierdo

Catalá

et al. 2014

Animal

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The present study was designed to evaluate the effect of activin-A during the in vitro oocyte maturation (IVM) and in vitro embryo culture (IVC) on nuclear maturation, blastocyst yield and blastocyst quality of prepubertal goat oocytes. In Experiment 1, three groups of oocytes were used during the IVM of prepubertal goat oocytes to determine the optimal concentration of recombinant human activin-A added to the maturation medium. Cumulus-oocyte complexes were matured in an IVM medium containing 0, 10 and 100 ng/ml (groups A0, A10 and A100), fertilized and in vitro cultured using standard procedures. In Experiment 2, the addition of 10 ng/ml activin-A at IVM (A10A0), IVC (A0A10) or IVM + IVC (A10A10) was studied and compared with the control group (A0A0). Results of the first experiment demonstrated that the addition of activin-A yielded similar percentages of maturation (⩽71.0%) and blastocyst formation rates (⩽24.9%) than the control group (A0). Experiment 2 showed that exposure of prepubertal goat oocytes to an IVC medium containing 10 ng/ml activin-A (A0A10) significantly increased the rates of development to the blastocyst stage, as compared with the control group (A0A0) (19.5 ± 2.21% v. 13.1 ± 2.37%, respectively; P < 0.05). With regard to the blastocyst quality, total number of cells, inner cell mass (ICM) and trophectoderm of prepubertal goat embryos produced in the presence of activin-A did not differ significantly among experimental groups. In summary, these results indicate that supplementation of the IVC medium with activin-A enhances embryo development of prepubertal goat oocytes.

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Activin a stimulates meiotic maturation of human oocytes and modulates granulosa cell steroidogenesis in vitro

Cited by 95 publications

References 21 publications

Regulation of ovarian function by the TGF-beta superfamily and follistatin

Regulation of ovarian function by the TGF-beta superfamily and follistatin

Potential local regulatory functions of inhibins, activins and follistatin in the ovary

In vitro developmental competence of prepubertal goat oocytes cultured with recombinant activin-A

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