Characterization of Inhibin/Activin Subunit, Activin Receptor, and Follistatin Messenger Ribonucleic Acid in Human and Mouse Oocytes: Evidence for Activin's Paracrine Signaling from Granulosa Cells to Oocytes1

Sidis, Yisrael; Fujiwara, Toshihiro; Leykin, Lucy; Isaacson, Keith; Toth, Thomas L.; Schneyer, Alan L.

doi:10.1095/biolreprod59.4.807

Cited by 96 publications

(59 citation statements)

References 41 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Gonadal inhibins and activins were first described as regulators of pituitary function, specifically for the regulation of FSH␤ expression (46 -49). Activin receptors (whose activities are possibly blocked by inhibins) have been found on oocytes (50). It is possible that these peptides may regulate oocyte development by modulating the expression and production of ovarian FSH␤ and LH␤.…”

Section: Discussionmentioning

confidence: 99%

Novel Expression of Gonadotropin Subunit Genes in Oocytes of the Gilthead Seabream (Sparus aurata)

Wong

Zohar

2004

Endocrinology

View full text Add to dashboard Cite

It is widely believed that FSH and LH, which are known to play key roles in controlling the production of functional oocytes in vertebrates, are synthesized and secreted exclusively by the anterior pituitary. Here we present evidence for the novel expression of FSH␤, LH␤, and the common glycoprotein-␣ (Cg␣) in the gilthead seabream ovary. Using in situ hybridization and immunocytochemistry, FSH␤ was detected in primary-growth and secondary-growth-I oocytes, LH␤ was found in secondary-growth oocytes, and Cg␣ was observed in both primary and secondary-growth oocytes. Northern blot analyses demonstrated that Fsh␤ transcript is 0.6 kb in both pituitary and ovary, whereas the ovarian Lh␤ transcript (1.1 kb), unexpectedly, is longer than the known pituitary Lh␤ transcript (0.6 kb). Sequence analyses revealed that ovarian T HE HYPOTHALAMIC-PITUITARY-GONADAL (HPG)axis is a fundamental component of the endocrine control of gametogenesis in which FSH and LH are integral endocrine messengers. In response to hypothalamic GnRH, pituitary FSH and LH are secreted into the circulation. Via the blood, they reach the gonad and bind to their respective G protein-coupled receptors, FSH receptor and LH receptor, on the ovarian follicle cells to coordinate the complex process of oocyte development. From studies of genetically derived reproductive defects in humans and mouse models, we have learned about the essential roles of FSH and LH in female reproduction (1-5). FSH acts on the granulosa cells to stimulate the activity of the aromatase system, which catalyzes the conversion of androgens into estrogens as well as to enhance the expression of LH receptor; LH plays a key role in thecal cell differentiation and promotes androgen production by these cells (6). In the late stages of follicular development, the action of LH on granulosa cells leads to the termination of their differentiation, induces oocyte meiotic maturation, and triggers follicular rupture (7,8).Oocyte development in teleosts can be divided into two major processes, follicular growth and final oocyte maturation (FOM). Follicular growth consists of two phases, the primary-growth (PG) phase and the secondary-growth (SG) phase. In the SG phase, oocytes undergo rapid growth associated with the uptake and accumulation of lipid and vitellogenin, i.e. vitellogenesis. Upon completion of the SG phase, the fully grown follicle is ready to undergo FOM, a series of developmental events preparing the oocyte for ovulation and fertilization. Pituitary gonadotropins are hormones of primary importance that trigger these two major processes. The actions of pituitary gonadotropins, however, are not direct but rather are mediated by the follicular steroids, estrogens for oocyte growth, and maturation-inducing hormone (MIH) for oocyte maturation (9).It has long been recognized that oocyte development is supported by the ovarian follicle cells, which not only mediate the FSH and LH signals from the endocrine system but also regulate the progression of oocyte development through autocrine ...

show abstract

Section: Discussionmentioning

confidence: 99%

Novel Expression of Gonadotropin Subunit Genes in Oocytes of the Gilthead Seabream (Sparus aurata)

Wong

Zohar

2004

Endocrinology

View full text Add to dashboard Cite

show abstract

“…However, it has been suggested that early mouse and human embryos, from the four-cell stage to the morula stage, are unable to synthesize activins, as no mRNA for these proteins has been identified at these stages of development (Lu et al 1993, He et al 1999. Furthermore, it has been proposed that activin, which binds to the activin type I and type II receptors on the preimplantation embryo, may be derived from the surrounding tissue such as the endosalpinx (He et al 1999), and that the oocyte is capable of receiving an activin signal produced by surrounding cumulus cells, but not of transmitting one (Sidis et al 1998). Moreover, it has been suggested that activin has a local paracrine or autocrine role with regard to early embryonic development as it is co-expressed with follistatin, the binding protein of activin, which would mitigate against tubal activin having a more distant site of action (Bahathiq et al 2002).…”

Section: Discussionmentioning

confidence: 99%

Production and localization of activins and activin type IIA and IIB receptors by the human endosalpinx

Refaat

Bahathiq²,

Sockanathan³

et al. 2004

Reproduction

View full text Add to dashboard Cite

Fallopian tubes from ten premenopausal women were collected and examined for the presence of inhibin, activin and its type IIA and IIB receptors (ActRIIA and ActRIIB) in the endosalpinx. Immunocytochemistry demonstrated clear staining for the bA, bB subunits and ActRIIA and ActRIIB that increased in intensity from the isthmus to the ampulla. No staining for the a subunit was observed. Whilst the staining of the bA subunit and ActRIIA was seen in almost every epithelial cell, staining for the bB subunit and ActRIIB was more variable. In situ hybridization and RT-PCR confirmed the presence of mRNA for the bA, bB subunits and ActRIIA and ActRIIB. These results indicated that the epithelium of the uterine tube is able to synthesize activin but not inhibin and has receptors for activin. Activins may thus act as paracrine regulators of tubal epithelial cell function, and embryonic activity may also bind to epithelial receptor and initiate intracellular processes that alter epithelial cell secretions.

show abstract

“…Cumulus granulosa cells surrounding the oocyte express inhibin/activin subunits (a, bA, bB) and follistatin (Roberts et al 1993, Sidis et al 1998, Izadyar et al 1998, Silva et al 2003, and the oocyte expresses both type-I and type-II activin receptors (Cameron et al 1994, Izadyar et al 1998, Sidis et al 1998. In both rodents and primates, activin A accelerates oocyte maturation (Sadatsuki et al 1993, Alak et al 1996 and in the bovine, oocyte developmental competence is improved (Silva & Knight 1998).…”

Section: Inhibin-activin Systemmentioning

confidence: 99%

TGF-β superfamily members and ovarian follicle development

Knight

Glister²

2006

Reproduction

1,062

786

View full text Add to dashboard Cite

In recent years, exciting progress has been made towards unravelling the complex intraovarian control mechanisms that, in concert with systemic signals, coordinate the recruitment, selection and growth of follicles from the primordial stage through to ovulation and corpus luteum formation. A plethora of growth factors, many belonging to the transforming growth factor-b (TGF-b) superfamily, are expressed by ovarian somatic cells and oocytes in a developmental, stage-related manner and function as intraovarian regulators of folliculogenesis. Two such factors, bone morphogenetic proteins, BMP-4 and BMP-7, are expressed by ovarian stromal cells and/or theca cells and have recently been implicated as positive regulators of the primordial-to-primary follicle transition. In contrast, evidence indicates a negative role for anti-Mullerian hormone (AMH, also known as Mullerianinhibiting substance) of pre-granulosa/granulosa cell origin in this key event and subsequent progression to the antral stage. Two other TGF-b superfamily members, growth and differentiation factor-9 (GDF-9) and BMP-15 (also known as GDF-9B) are expressed in an oocyte-specific manner from a very early stage and play key roles in promoting follicle growth beyond the primary stage; mice with null mutations in the gdf-9 gene or ewes with inactivating mutations in gdf-9 or bmp-15 genes are infertile with follicle development arrested at the primary stage. Studies on later stages of follicle development indicate positive roles for granulosa cell-derived activin, BMP-2, -5 and -6, theca cell-derived BMP-2, -4 and -7 and oocyte-derived BMP-6 in promoting granulosa cell proliferation, follicle survival and prevention of premature luteinization and/or atresia. Concomitantly, activin, TGF-b and several BMPs may exert paracrine actions on theca cells to attenuate LH-dependent androgen production in small to medium-size antral follicles. Dominant follicle selection in monovular species may depend on differential FSH sensitivity amongst a growing cohort of small antral follicles. Changes in intrafollicular activins, GDF-9, AMH and several BMPs may contribute to this selection process by modulating both FSH-and IGF-dependent signalling pathways in granulosa cells. Activin may also play a positive role in oocyte maturation and acquisition of developmental competence. In addition to its endocrine role to suppress FSH secretion, increased output of inhibin by the selected dominant follicle(s) may upregulate LH-induced androgen secretion that is required to sustain a high level of oestradiol secretion during the pre-ovulatory phase. Advances in our understanding of intraovarian regulatory mechanisms should facilitate the development of new approaches for monitoring and manipulating ovarian function and improving fertility in domesticated livestock, endangered species and man.

show abstract

Characterization of Inhibin/Activin Subunit, Activin Receptor, and Follistatin Messenger Ribonucleic Acid in Human and Mouse Oocytes: Evidence for Activin's Paracrine Signaling from Granulosa Cells to Oocytes1

Cited by 96 publications

References 41 publications

Novel Expression of Gonadotropin Subunit Genes in Oocytes of the Gilthead Seabream (Sparus aurata)

Novel Expression of Gonadotropin Subunit Genes in Oocytes of the Gilthead Seabream (Sparus aurata)

Production and localization of activins and activin type IIA and IIB receptors by the human endosalpinx

TGF-β superfamily members and ovarian follicle development

Contact Info

Product

Resources

About