Volume 22, Issue 1 e12538

REVIEW

Open Access

Paracrine regulation of granulosa cell development in the antral follicles in mammals

Koji Sugiura,

Corresponding Author

Koji Sugiura

[email protected]

orcid.org/0000-0001-8945-3353

Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan

Correspondence

Koji Sugiura, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.

Email: [email protected]

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Natsumi Maruyama,

Natsumi Maruyama

Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan

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Yuki Akimoto,

Yuki Akimoto

Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan

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Kodai Matsushita,

Kodai Matsushita

Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan

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Tsutomu Endo,

Tsutomu Endo

Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan

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Koji Sugiura,

Corresponding Author

Koji Sugiura

[email protected]

orcid.org/0000-0001-8945-3353

Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan

Correspondence

Koji Sugiura, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.

Email: [email protected]

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Natsumi Maruyama,

Natsumi Maruyama

Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan

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Yuki Akimoto,

Yuki Akimoto

Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan

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Kodai Matsushita,

Kodai Matsushita

Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan

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Tsutomu Endo,

Tsutomu Endo

Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan

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First published: 26 August 2023

https://doi.org/10.1002/rmb2.12538

Citations: 4

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Abstract

Background

Development of ovarian follicles is regulated by a complex interaction of intra- and extra-follicular signals. Oocyte-derived paracrine factors (ODPFs) play a central role in this process in cooperation with other signals.

Methods

This review provides an overview of the recent advances in our understanding of the paracrine regulation of antral follicle development in mammals. It specifically focuses on the regulation of granulosa cell development by ODPFs, along with other intrafollicular signals.

Main Findings

Bi-directional communication between oocytes and surrounding cumulus cells is a fundamental mechanism that determines cumulus cell differentiation. Along with estrogen, ODPFs promote the expression of forkhead box L2, a critical transcription factor required for mural granulosa cells. Follicle-stimulating hormone (FSH) facilitates these processes by stimulating estrogen production in mural granulosa cells.

Conclusion

Cooperative interactions among ODPFs, FSH, and estrogen are critical in determining the fate of cumulus and mural granulosa cells, as well as the development of oocytes.

1 INTRODUCTION

Ovary plays a central role in the female reproductive system by producing functional oocytes capable of undergoing fertilization and embryogenesis and secreting several steroid hormones as part of its endocrine function. To achieve this, the normal development and function of ovarian follicles are crucial, with the oocyte playing a central role in this process. In fact, in mice, when follicles are reconstructed from oocytes and somatic cells collected separately from follicles at different developmental stages, the developmental stage of the follicle synchronizes with that of the oocyte rather than with that of the somatic cells.¹ Therefore, the developmental stage of the follicle is determined by the oocyte, and this appears to be an important mechanism for establishing a suitable follicular environment for the developmental stage of the oocyte itself.

Many studies investigated the mechanism by which oocytes coordinate follicular development and function. These studies have identified critical growth factors produced by oocytes that are required for normal folliculogenesis. Oocyte-derived paracrine factors (ODPFs) regulate the way how follicular somatic cells, namely granulosa cells, respond to extra- and intrafollicular signals, profoundly by affecting the gene expression in these cells. In this review, we summarize the current understanding of paracrine regulation of antral follicle development, with an emphasis on the regulation of granulosa cell development by ODPFs and other intrafollicular signals in mammals.

2 FOLLICULOGENESIS

Follicular development begins with the formation of primordial follicles (Figure 1). Primordial follicles consist of a layer of squamous somatic cells, often called “pre-granulosa cells,” surrounding an immature and quiescent oocyte. The ovary contains thousands to millions of primordial follicles in a dormant state, which serve as a pool of oocytes produced by the animal throughout its lifetime. Some of the dormant primordial follicles initiate growth and progress to become primary follicles, where the oocyte starts to grow and the surrounding somatic cells transform into cuboidal morphology. The somatic cells surrounding the oocyte at this stage are now called “granulosa cells.” Formation and activation of primordial follicles are affected by oocytes, as evidenced by the ovarian phenotypes of mutant mouse models. For example, the ovaries of mice deficient in Figla (folliculogenesis specific basic helix–loop–helix) and Pten (phosphatase and tensin homolog) exhibit no primordial follicles and activation of entire pool of primordial follicles and consequent premature ovarian failure, respectively.^{2, 3}

Details are in the caption following the image — **FIGURE 1**
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Overview of folliculogenesis in mice.

When the granulosa cells of the primary follicle continue to proliferate and form multiple cell layers, the follicle is called a secondary follicle, and the granulosa cells become round shape in mice. As a secondary follicle develops into a tertiary follicle, a fluid-filled cavity called the antrum is formed within the follicle. Hence, the tertiary follicle is also known as an “antral follicle,” while the secondary follicle is often referred to as a “preantral follicle.” Antrum formation appears to be dependent on oocytes, as shown in experiments in which oocytes or recombinant proteins of ODFPs promoted antrum formation in isolated granulosa cell complexes in vitro.^{4, 5}

Formation of the antral cavity physically divides granulosa cells into two sub-populations in the antral follicles: cumulus cells and mural granulosa cells. Cumulus cells are located close proximate to oocytes and play a pivotal role in supporting oocyte development. In contrast, mural granulosa cells are located far from oocytes at the wall of the follicle and primarily perform endocrine functions such as estrogen production. In comparison to these granulosa cell populations in antral follicles, granulosa cells of preantral follicles (i.e., secondary follicles) are sometimes referred to as “preantral granulosa cells.” Normal development of these granulosa cell populations is crucial for ovarian function and, therefore, for normal female fertility.

3 BI-DIRECTIONAL COMMUNICATIONS BETWEEN OOCYTES AND CUMULUS CELLS

Cumulus cells contact oocytes through narrow cytoplasmic extensions known as transzonal projections (TZPs) that penetrate the zona pellucida.^{6, 7} At the end of TZPs, cumulus cells form heterologous gap junctions with oocytes and support oocyte development by supplying small-molecule substances, such as metabolic products.⁸ For example, oocytes do not express enzymes in the glycolytic pathway and therefore cannot efficiently utilize glucose as an energy substrate.⁹ In contrast, cumulus cells have high glycolytic activity, actively metabolize glucose, and supply metabolic products (such as pyruvate) to the oocytes.^{10, 11} Through this process, cumulus cells support the energy metabolism of oocytes. Similarly, cumulus cells supply substances that oocytes are not capable of producing or taking up, such as cholesterol and certain amino acids, to support oocyte development.^12-14 Moreover, oocytes depend on cumulus cells for transcriptional regulation¹⁵ and meiotic controls.¹⁶

In contrast, oocytes are not merely the recipients of support from cumulus cells; rather, they actively participate in regulating the development and function of cumulus cells by secreting various growth factors. For example, oocytes promote the proliferation of cumulus cells,¹⁷ prevent apoptosis,¹⁸ and, at least in mice, enable cumulus expansion, a prerequisite process for normal ovulation.^{19, 20} Moreover, the aforementioned metabolic activities in cumulus cells, that is, glycolysis, amino acid uptake, and cholesterol biosynthesis, are also regulated by oocytes.^{12, 21, 22} In addition, while meiotic arrest of oocytes requires cyclic guanosine monophosphate (cGMP) supplied from cumulus cells through gap junctions, cGMP production by cumulus cells is regulated by oocytes.²³

Therefore, while oocytes regulate the development and function of cumulus cells, cumulus cells support the normal development of oocytes. This bi-directional communication between oocytes and cumulus cells is an essential mechanism for the normal development of both cell types.

4 OOCYTE-DERIVED PARACRINE FACTORS (ODPFS)

4.1 Members of transforming growth factor beta (TGF-β) superfamily

The critical requirement for ODPFs in normal follicular development was first reported in a study using a mutant mouse model deficient in growth differentiation factor 9 (GDF9), an oocyte-secreted member of the TGF-β superfamily.²⁴ Female mice deficient in Gdf9 gene exhibit infertility due to the arrest of follicular development at the primary follicle stage.^{24, 25} Similarly, in vivo administration of GDF9 or treatment with GDF9 in ovarian organ cultures has been shown to stimulate primary follicle progression in rats.^{26, 27} Moreover, in human ovarian organ cultures, treatment with GDF9 promotes survival and progression of follicular development to the secondary stage.²⁸ Therefore, GDF9 promotes follicular development during the early stages.

The arrest of follicular development in Gdf9-deficient mice appears to be attributable to increased production of inhibin, which suppresses the proliferation of granulosa cells.²⁹ In fact, in the ovaries of mice deficient in both Gdf9 and inhibin α genes, the arrest of follicular development was not observed, and follicles develop beyond the secondary stage. However, these mice eventually develop granulosa cell tumors and become infertile.²⁹

Because the ovaries of Gdf9-deficient mice exhibit folliculogenesis arrest at the primary follicle stage, the role of GDF9 in the later stages of follicular development has mainly been studied using recombinant proteins. These studies have shown in mice that GDF9 promotes the proliferation of granulosa cells,^{30, 31} suppresses the expression of luteinizing hormone receptor (LHCGR) in cumulus cells,³² and promotes cumulus expansion,³² thus, highlighting its crucial role in the regulation of granulosa cell differentiation and function in the later stages of follicular development. Moreover, recombinant GDF9 and/or oocyte coculture can enhance the developmental competence of oocytes in cattle,³³ mice,³⁴ goats,³⁵ and pigs.³⁶

Oocytes also produce bone morphogenetic proteins (BMPs), such as BMP15 and BMP6, which are the other members of the TGF-β superfamily. The profound requirement of BMP15 for female fertility was first reported in sheep. Inverdale and Hanna sheep carrying a naturally occurring mutation in BMP15 gene exhibited increased ovulation rates in heterozygotes, whereas homozygotes exhibit primary ovarian failure due to impaired follicular development beyond the primary stage.³⁷ Similarly, sheep carrying mutations in genes encoding BMP receptors exhibited increased ovulation rate.^38-40

In contrast to sheep, mice deficient in Bmp15 gene show no significant abnormalities in the developmental dynamics of follicles; however, they are subfertile due to decreased ovulation and fertilization rates.⁴¹ Similarly, female mice deficient in Bmp6 or both Bmp15 and Bmp6 genes exhibit reduced ovulation and fertilization rates and are subfertile.⁴² On the other hand, the ovaries of mice deficient in the genes encoding SMAD1/5/8, which are intracellular mediators of BMP signaling, develop granulosa cell tumors, ultimately resulting in infertility.^{43, 44} Moreover, deficiency in the BMP receptor gene Bmpr1b results in female infertility and functional ovarian defects including lower aromatase production in granulosa cells.⁴⁵ These findings suggest that an intrafollicular BMP signal consisting of BMP15 and BMP6 produced by oocytes, together with BMPs derived from other cells within the follicle, is essential for normal female fertility in mice.

BMP15 and GDF9 have also been implicated in fertility of woman. For example, mature GDF9 levels in follicular fluid significantly correlated with oocyte nuclear maturation and embryo quality in patients who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI).⁴⁶ Mutations in the GDF9 genes are significantly correlated with dizygotic twinning.^{47, 48} Moreover, the association of mutations in the GDF9^49-52 and BMP15^{50, 53-57} genes with primary ovarian insufficiency (POI) has been reported. In addition, dysregulation of BMPR1B in granulosa cells is associated with reduced ovarian reserves and age-related decline in human fertility.⁵⁸

Synergistic interaction between BMP15 and GDF9 has been reported in the regulation of granulosa cell development. For instance, as mentioned earlier, while Bmp15-deficient mice exhibit relatively mild ovarian defects, mice with an additional heterozygous deletion of Gdf9 (i.e., Bmp15^−/−/Gdf9^+/−) show more severe ovarian abnormalities and become infertile.⁴¹ Although the precise mechanisms underlying the synergistic function of BMP15 and GDF9 require further investigation, heterodimerization of BMP15 and GDF9 is likely to be involved. This BMP15/GDF9 heterodimer, known as cumulin, exhibits higher activity than the homodimers of BMP15 or GDF9.⁵⁹ More recently, highly potent GDF9 variant, designated as “super-GDF9,” has been developed.⁶⁰ Both cumulin and Super-GDF9 have been reported to improve the developmental potential of mouse oocytes in culture, and their application is anticipated to enhance oocyte development in livestock and infertility treatment in humans.^{61, 62}

4.2 Fibroblast growth factors (FGFs)

Another growth factor family produced by mammalian oocytes is FGFs. Expression of FGF8 by oocytes has been reported in several mammalian species, including mice⁶³ and cows.⁶⁴ Although FGF8 transcript was not detected in normal human ovaries, it was detected in ovarian tumors and cancer cell lines.⁶⁵ These findings suggest that FGF8 plays an important role in ovarian tumorigenesis in human. Furthermore, FGF17, one of the FGF8 subfamily ligands, is expressed by oocytes in mice,⁶⁶ and by oocytes, theca cells, and granulosa cells in cows.⁶⁷ Other FGF8 subfamily ligand, FGF18, is expressed by mouse oocytes, but not by bovine oocytes; instead, FGF18 was detected in bovine theca, granulosa, and luteal cells.⁶⁸ Moreover, the expression of FGF receptors has been reported in granulosa cells of various mammalian species, including mice, rats, cows, and humans.^{64, 69-73}

As mentioned above, mouse oocytes promote glycolysis in the surrounding cumulus cells and utilize the metabolic products provided by the cumulus cells as energy substrates.²² One of the ODPFs that control glycolysis in cumulus cells is FGF8.⁷⁴ FGF8 cooperates with BMP15 to promote the expression of glycolytic enzymes, such as PFKP and LDHA, by cumulus cells, thereby enhancing glycolytic activity in these cells. SPRY2, an antagonist of FGF signaling, has been implicated in the coordinated action of FGF8 and BMP15.⁷⁵ A cooperative interaction between FGF8 and BMP signaling has also been reported in rats. FGF8 promotes the suppressive effects of BMPs on follicle-stimulating hormone (FSH)-induced cyclic adenosine monophosphate (cAMP) production and BMP-stimulated SMAD1/5/8 phosphorylation in rat preantral granulosa cells.⁷⁶

Ovarian follicles are enriched in FGF signals, and many studies have emphasized the importance of FGFs in the regulation of ovarian function. In fact, mice carrying mutations in FGF receptor genes have been reported to exhibit female infertility.^77-79 However, compared to the TGF-β superfamily, there is relatively limited in vivo evidence regarding the requirement of FGF signaling in normal follicle development, such as the phenotypes observed in knockout mouse models. Future studies involving the conditional deletion of genes encoding FGF ligands and receptors are crucial to gain a deeper understanding of FGF function in the ovaries and its impact on female fertility.

5 DIFFERENTIATION BETWEEN CUMULUS AND MURAL GRANULOSA CELLS

5.1 Intrafollicular signal gradients of FSH and ODPFs

Both cumulus and mural granulosa cells differentiate from preantral granulosa cells during the transition from preantral to antral follicles. The currently accepted model for the regulation of the differentiation of these cell types is that preantral granulosa cells located near the oocytes differentiate into cumulus cells under the influence of ODPFs (Figure 2). In contrast, preantral granulosa cells located relatively far from the oocytes differentiate into mural granulosa cells. Differentiation into mural granulosa cells depends to a great extent on FSH from the pituitary gland. Therefore, the differentiation and function of cumulus and mural granulosa cells are determined by opposing signal gradients within a follicle, with FSH signaling from outside the follicle and ODPFs signaling from inside.⁸⁰

In addition to ODPFs and FSH, normal follicular development requires signals of estrogen. In fact, the disruption of estrogen signaling by deletion of the Esr2 gene encoding estrogen receptor 2 (also known as estrogen receptor-β), a predominant estrogen receptor expressed by granulosa cells, results in female subfertility,⁸¹ attenuated follicular development^81-83; and reduced ovulation rates in mice.^{81, 84} Moreover, loss of both Esr1 (encoding estrogen receptor-α) and Esr2 results in female infertility associated with granulosa cell defects.⁸⁵ Our study also revealed that the cooperative interaction between oocyte and estrogen signals is critical for the normal development and function of cumulus cells in mice.^86-88 Therefore, estrogen is critical for the development and function of both cumulus cells and mural granulosa cells.

A comprehensive analysis of cellular transcripts is a valuable approach for understanding the processes and regulation of cell differentiation and function. We have previously attempted to elucidate the differentiation processes and regulatory mechanisms of cumulus and mural granulosa cells through transcriptomic analysis.^{12, 87, 89, 90} According to these studies, there are significant differences in the expression of over 3000 genes between cumulus and mural granulosa cells.⁸⁹ Transcripts highly represented in cumulus cells are often associated with cell proliferation and metabolism-related processes such as glycolysis and cholesterol production, whereas those related to steroid production show higher expression in mural granulosa cells. These transcriptomic differences between these cell types are in agreement with in vitro experiments showing that oocytes promote the expression of transcripts encoding enzymes involved in glycolysis and cholesterol biosynthesis in cumulus cells,^{12, 22, 74} whereas FSH regulates the expression of enzymes involved in steroid synthesis in mural granulosa cells.^{91, 92} Furthermore, by comparing these data with the transcriptomic differences between cumulus cells of Bmp15^−/−/Gdf9^+/− mice and wild-type mice¹² and the changes in gene expression upon stimulation of cumulus cells with ODPFs,⁸⁷ it was suggested that approximately half of the significantly upregulated genes in cumulus cells compared to mural granulosa cells are directly regulated by oocytes.⁸⁹ These findings strongly support the importance of oocyte-derived signals in cumulus cell differentiation.

Although the importance of ODPFs in the development of cumulus cells has been reported, oocytes are also required for the development and maintenance of mural granulosa cells. For example, in the reconstructed follicles where the somatic cells of newborn ovaries were combined with mid-growth stage oocytes, the development of not only cumulus cells but also that of mural granulosa cells was accelerated.¹ Moreover, removing cumulus-oocyte complexes from antral follicles in rabbits results in precocious luteinization of mural granulosa cells,⁹³ and oocytes suppress the luteinization of cultured mural granulosa cells in rats.⁹⁴ These observations indicate that oocyte-derived signals are required not only for the development of mural granulosa cells but also for maintaining the characteristics of mural granulosa cells; however, the mechanism by which oocytes influence these processes is not well understood.

5.2 Forkhead box L2 (FOXL2): A transcriptional regulator of cumulus and mural granulosa cell differentiations

To explore the basic mechanisms that determine the transcriptomic differences between cumulus and mural granulosa cells, we attempted to identify the “transcriptional regulators” controlling the differences in gene expression between these two granulosa cell populations using mice as a model.⁹⁰ The results showed that a transcription factor FOXL2 is a critical transcriptional regulator responsible for the differentiation of mural granulosa cells. In fact, the target transcripts of FOXL2 are enriched in those involved in steroid metabolism, which is one of the critical functions of mural granulosa cells, but not cumulus cells.⁹⁵

FOXL2 is an essential transcription factor involved in normal ovarian development and function. In Foxl2-deficient ovaries, granulosa cells do not complete the squamous-to-cuboidal transition, which normally occurs during the transition from primordial to primary follicles, and result in infertility.^{96, 97} In contrast, when Foxl2 genes are deleted in the ovaries of adult mice, developing granulosa cells become express testis-specific genes such as SOX9 and sexually transdifferentiate into Sertoli cell-like cells.⁹⁸ In humans, mutations in FOXL2 gene cause the blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), which is often associated with POI.⁹⁹ Additionally, approximately 97% of adult-type granulosa cell tumors harbor a somatic missense mutation in the FOXL2 gene.^{100, 101} Based on these findings, FOXL2 is considered an essential transcription factor for the development and maintenance of granulosa cells.

We previously reported in mice that FOXL2 expression increases during the development of mural granulosa cells, while it is maintained at a lower level in cumulus cells due to suppression by ODPFs.⁸⁸ In addition, the high level of FOXL2 expression in mural granulosa cells requires the stimulation of both ODPFs and estrogen.¹⁰² Therefore, oocytes exert two antagonistic effects on FOXL2 expression during granulosa cell differentiation: they cooperate with estrogen signaling to promote mural granulosa cell differentiation by enhancing FOXL2 expression and facilitate cumulus cell differentiation by suppressing FOXL2 expression.

Ovarian follicles are composed of various cell types including oocytes, cumulus cells, and mural granulosa cells. The coordinated development and function of each cell type is crucial for normal ovarian function and female fertility (Figure 3). Bi-directional communication between oocytes and cumulus cells is essential for the normal development of both cell types.^{8, 103} Mural granulosa cells facilitate this bi-directional communication by producing estrogen since ODPFs and estrogen cooperatively regulate the development and function of cumulus cells.^{86, 87} At the sametime, along with estrogen, oocytes regulate the development and function of mural granulosa cells by promoting FOXL2 expression.^{88, 102} Importantly, estrogen production by mural granulosa cells is controlled by FSH.^104-106 Therefore, FSH indirectly influences oocyte development by promoting cumulus cell development via estrogen, at least, in mice. These interactions are likely part of the complex regulatory network governing granulosa cell development and warrant further research. Furthermore, since these studies were conducted in mice, it is important to determine whether a similar mechanism exists in other mammals.

In addition to FOXL2 expression, differences are observed in the expression of epigenetic regulators between cumulus and mural granulosa cells.⁸⁸ Therefore, epigenetic regulation may play a role in determining the fate of these cells. Further investigation of these factors will provide deeper insights into the cellular mechanisms regulating the differentiation of cumulus and mural granulosa cells.

6 CONCLUSION

The potential importance of nutrient support from the surrounding granulosa cells during oocyte development was first noted over 100 years ago.¹⁰⁷ Subsequent studies have shed light on the regulation of granulosa cell differentiation and revealed many roles played by them. These studies have greatly improved our understanding of follicular development. However, the specific mechanism involved remains unclear. Recent advances in next-generation sequencing and genome-editing technologies have drastically accelerated the research progress. Further investigations using these advanced techniques will accelerate our understanding of follicular development and aid in the production of efficient assisted reproductive technologies.

ACKNOWLEDGEMENTS

The authors are grateful to the members of the Laboratory of Applied Genetics (The University of Tokyo) for their helpful input and critical reading of this manuscript. This work was supported by the Japan Society for the Promotion of Science (grant/award numbers: JP23H02359, JP21K19183, and JP20H03124).

CONFLICT OF INTEREST STATEMENT

The authors declare no conflict of interest.

REFERENCES

1Eppig JJ, Wigglesworth K, Pendola FL. The mammalian oocyte orchestrates the rate of ovarian follicular development. Proc Natl Acad Sci USA. 2002; 99: 2890–2894.
10.1073/pnas.052658699
CAS PubMed Web of Science® Google Scholar
2Soyal SM, Amleh A, Dean J. FIGalpha, a germ cell-specific transcription factor required for ovarian follicle formation. Development. 2000; 127: 4645–4654.
10.1242/dev.127.21.4645
CAS PubMed Web of Science® Google Scholar
3Reddy P, Liu L, Adhikari D, Jagarlamudi K, Rajareddy S, Shen Y, et al. Oocyte-specific deletion of Pten causes premature activation of the primordial follicle pool. Science. 2008; 319: 611–613.
10.1126/science.1152257
CAS PubMed Web of Science® Google Scholar
4Shen X, Miyano T, Kato S. Promotion of follicular antrum formation by pig oocytes in vitro. Zygote (Cambridge, England). 1998; 6: 47–54.
10.1017/S0967199400005074
CAS PubMed Web of Science® Google Scholar
5Alam MH, Lee J, Miyano T. GDF9 and BMP15 induce development of antrum-like structures by bovine granulosa cells without oocytes. J Reprod Dev. 2018; 64: 423–431.
10.1262/jrd.2018-078
CAS PubMed Web of Science® Google Scholar
6Anderson E, Albertini DF. Gap junctions between the oocyte and companion follicle cells in the mammalian ovary. J Cell Biol. 1976; 71: 680–686.
10.1083/jcb.71.2.680
CAS PubMed Web of Science® Google Scholar
7El-Hayek S, Yang Q, Abbassi L, FitzHarris G, Clarke HJ. Mammalian oocytes locally remodel follicular architecture to provide the Foundation for Germline-Soma Communication. Curr Biol. 2018; 28: 1124–1131.e3.
10.1016/j.cub.2018.02.039
CAS PubMed Web of Science® Google Scholar
8Su YQ, Sugiura K, Eppig JJ. Mouse oocyte control of granulosa cell development and function: paracrine regulation of cumulus cell metabolism. Semin Reprod Med. 2009; 27: 32–42.
10.1055/s-0028-1108008
CAS PubMed Web of Science® Google Scholar
9Biggers JD, Whittingham DG, Donahue RP. The pattern of energy metabolism in the mouse oocyte and zygote. Proc Natl Acad Sci USA. 1967; 58: 560–567.
10.1073/pnas.58.2.560
CAS PubMed Web of Science® Google Scholar
10Donahue RP, Stern S. Follicular cell support of oocyte maturation: production of pyruvate in vitro. J Reprod Fertil. 1968; 17: 395–398.
10.1530/jrf.0.0170395
CAS PubMed Web of Science® Google Scholar
11Leese HJ, Barton AM. Production of pyruvate by isolated mouse cumulus cells. J Exp Zool. 1985; 234: 231–236.
10.1002/jez.1402340208
CAS PubMed Web of Science® Google Scholar
12Su YQ, Sugiura K, Wigglesworth K, O'Brien MJ, Affourtit JP, Pangas SA, et al. Oocyte regulation of metabolic cooperativity between mouse cumulus cells and oocytes: BMP15 and GDF9 control cholesterol biosynthesis in cumulus cells. Development. 2008; 135: 111–121.
10.1242/dev.009068
CAS PubMed Web of Science® Google Scholar
13Cecconi S, Rossi G, De Felici M, Colonna R. Mammalian oocyte growth in vitro is stimulated by soluble factor(s) produced by preantral granulosa cells and by Sertoli cells. Mol Reprod Dev. 1996; 44: 540–546.
10.1002/(SICI)1098-2795(199608)44:4<540::AID-MRD14>3.0.CO;2-1
CAS PubMed Web of Science® Google Scholar
14Haghighat N, Van Winkle LJ. Developmental change in follicular cell-enhanced amino acid uptake into mouse oocytes that depends on intact gap junctions and transport system Gly. J Exp Zool. 1990; 253: 71–82.
10.1002/jez.1402530110
CAS PubMed Web of Science® Google Scholar
15De La Fuente R, Eppig JJ. Transcriptional activity of the mouse oocyte genome: companion granulosa cells modulate transcription and chromatin remodeling. Dev Biol. 2001; 229(1): 224–236.
10.1006/dbio.2000.9947
CAS PubMed Web of Science® Google Scholar
16Norris RP, Ratzan WJ, Freudzon M, Mehlmann LM, Krall J, Movsesian MA, et al. Cyclic GMP from the surrounding somatic cells regulates cyclic AMP and meiosis in the mouse oocyte. Development. 2009; 136: 1869–1878.
10.1242/dev.035238
CAS PubMed Web of Science® Google Scholar
17Vanderhyden BC, Telfer EE, Eppig JJ. Mouse oocytes promote proliferation of granulosa cells from preantral and antral follicles in vitro. Biol Reprod. 1992; 46: 1196–1204.
10.1095/biolreprod46.6.1196
CAS PubMed Web of Science® Google Scholar
18Hussein TS, Froiland DA, Amato F, Thompson JG, Gilchrist RB. Oocytes prevent cumulus cell apoptosis by maintaining a morphogenic paracrine gradient of bone morphogenetic proteins. J Cell Sci. 2005; 118: 5257–5268.
10.1242/jcs.02644
CAS PubMed Web of Science® Google Scholar
19Buccione R, Vanderhyden BC, Caron PJ, Eppig JJ. FSH-induced expansion of the mouse cumulus oophorus in vitro is dependent upon a specific factor(s) secreted by the oocyte. Dev Biol. 1990; 138: 16–25.
10.1016/0012-1606(90)90172-F
CAS PubMed Web of Science® Google Scholar
20Salustri A, Ulisse S, Yanagishita M, Hascall VC. Hyaluronic acid synthesis by mural granulosa cells and cumulus cells in vitro is selectively stimulated by a factor produced by oocytes and by transforming growth factor-beta. J Biol Chem. 1990; 265: 19517–19523.
10.1016/S0021-9258(17)45403-2
CAS PubMed Web of Science® Google Scholar
21Eppig JJ, Pendola FL, Wigglesworth K, Pendola JK. Mouse oocytes regulate metabolic cooperativity between granulosa cells and oocytes: amino acid transport. Biol Reprod. 2005; 73: 351–357.
10.1095/biolreprod.105.041798
CAS PubMed Web of Science® Google Scholar
22Sugiura K, Pendola FL, Eppig JJ. Oocyte control of metabolic cooperativity between oocytes and companion granulosa cells: energy metabolism. Dev Biol. 2005; 279: 20–30.
10.1016/j.ydbio.2004.11.027
CAS PubMed Web of Science® Google Scholar
23Zhang M, Su YQ, Sugiura K, Eppig JJ. Granulosa cell ligand NPPC and its receptor NPR2 maintain meiotic arrest in mouse oocytes. Science. 2010; 330: 366–369.
10.1126/science.1193573
CAS PubMed Web of Science® Google Scholar
24Dong J, Albertini DF, Nishimori K, Kumar TR, Lu N, Matzuk MM. Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature. 1996; 383: 531–535.
10.1038/383531a0
CAS PubMed Web of Science® Google Scholar
25Carabatsos MJ, Elvin J, Matzuk MM, Albertini DF. Characterization of oocyte and follicle development in growth differentiation factor-9-deficient mice. Dev Biol. 1998; 204: 373–384.
10.1006/dbio.1998.9087
CAS PubMed Web of Science® Google Scholar
26Vitt UA, McGee EA, Hayashi M, Hsueh AJ. In vivo treatment with GDF-9 stimulates primordial and primary follicle progression and theca cell marker CYP17 in ovaries of immature rats. Endocrinology. 2000; 141: 3814–3820.
10.1210/endo.141.10.7732
CAS PubMed Web of Science® Google Scholar
27Nilsson EE, Skinner MK. Growth and differentiation factor-9 stimulates progression of early primary but not primordial rat ovarian follicle development. Biol Reprod. 2002; 67: 1018–1024.
10.1095/biolreprod.101.002527
CAS PubMed Web of Science® Google Scholar
28Hreinsson JG, Scott JE, Rasmussen C, Swahn ML, Hsueh AJ, Hovatta O. Growth differentiation factor-9 promotes the growth, development, and survival of human ovarian follicles in organ culture. J Clin Endocrinol Metab. 2002; 87: 316–321.
10.1210/jcem.87.1.8185
CAS PubMed Web of Science® Google Scholar
29Wu X, Chen L, Brown CA, Yan C, Matzuk MM. Interrelationship of growth differentiation factor 9 and inhibin in early folliculogenesis and ovarian tumorigenesis in mice. Mol Endocrinol. 2004; 18: 1509–1519.
10.1210/me.2003-0399
CAS PubMed Web of Science® Google Scholar
30Vitt UA, Hayashi M, Klein C, Hsueh AJ. Growth differentiation factor-9 stimulates proliferation but suppresses the follicle-stimulating hormone-induced differentiation of cultured granulosa cells from small antral and preovulatory rat follicles. Biol Reprod. 2000; 62: 370–377.
10.1095/biolreprod62.2.370
CAS PubMed Web of Science® Google Scholar
31Gilchrist RB, Ritter LJ, Myllymaa S, Kaivo-Oja N, Dragovic RA, Hickey TE, et al. Molecular basis of oocyte-paracrine signalling that promotes granulosa cell proliferation. J Cell Sci. 2006; 119: 3811–3821.
10.1242/jcs.03105
CAS PubMed Web of Science® Google Scholar
32Elvin JA, Clark AT, Wang P, Wolfman NM, Matzuk MM. Paracrine actions of growth differentiation factor-9 in the mammalian ovary. Mol Endocrinol. 1999; 13: 1035–1048.
10.1210/mend.13.6.0310
CAS PubMed Web of Science® Google Scholar
33Hussein TS, Thompson JG, Gilchrist RB. Oocyte-secreted factors enhance oocyte developmental competence. Dev Biol. 2006; 296: 514–521.
10.1016/j.ydbio.2006.06.026
CAS PubMed Web of Science® Google Scholar
34Yeo CX, Gilchrist RB, Thompson JG, Lane M. Exogenous growth differentiation factor 9 in oocyte maturation media enhances subsequent embryo development and fetal viability in mice. Hum Reprod. 2008; 23: 67–73.
10.1093/humrep/dem140
CAS PubMed Web of Science® Google Scholar
35Romaguera R, Morató R, Jiménez-Macedo AR, Catalá M, Roura M, Paramio MT, et al. Oocyte secreted factors improve embryo developmental competence of COCs from small follicles in prepubertal goats. Theriogenology. 2010; 74: 1050–1059.
10.1016/j.theriogenology.2010.04.035
CAS PubMed Web of Science® Google Scholar
36Gomez MN, Kang JT, Koo OJ, Kim SJ, Kwon DK, Park SJ, et al. Effect of oocyte-secreted factors on porcine in vitro maturation, cumulus expansion and developmental competence of parthenotes. Zygote (Cambridge, England). 2012; 20: 135–145.
10.1017/S0967199411000256
CAS PubMed Web of Science® Google Scholar
37Galloway SM, McNatty KP, Cambridge LM, Laitinen MP, Juengel JL, Jokiranta TS, et al. Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner. Nat Genet. 2000; 25: 279–283.
10.1038/77033
CAS PubMed Web of Science® Google Scholar
38Wilson T, Wu XY, Juengel JL, Ross IK, Lumsden JM, Lord EA, et al. Highly prolific Booroola sheep have a mutation in the intracellular kinase domain of bone morphogenetic protein IB receptor (ALK-6) that is expressed in both oocytes and granulosa cells. Biol Reprod. 2001; 64: 1225–1235.
10.1095/biolreprod64.4.1225
CAS PubMed Web of Science® Google Scholar
39Souza CJ, MacDougall C, Campbell BK, McNeilly AS, Baird DT. The Booroola (FecB) phenotype is associated with a mutation in the bone morphogenetic receptor type 1 B (BMPR1B) gene. J Endocrinol. 2001; 169: R1–R6.
10.1677/joe.0.169r001
CAS PubMed Web of Science® Google Scholar
40Mulsant P, Lecerf F, Fabre S, Schibler L, Monget P, Lanneluc I, et al. Mutation in bone morphogenetic protein receptor-IB is associated with increased ovulation rate in Booroola Merino ewes. Proc Natl Acad Sci USA. 2001; 98: 5104–5109.
10.1073/pnas.091577598
CAS PubMed Web of Science® Google Scholar
41Yan C, Wang P, DeMayo J, DeMayo FJ, Elvin JA, Carino C, et al. Synergistic roles of bone morphogenetic protein 15 and growth differentiation factor 9 in ovarian function. Mol Endocrinol. 2001; 15: 854–866.
10.1210/mend.15.6.0662
CAS PubMed Web of Science® Google Scholar
42Sugiura K, Su YQ, Eppig JJ. Does bone morphogenetic protein 6 (BMP6) affect female fertility in the mouse? Biol Reprod. 2010; 83: 997–1004.
10.1095/biolreprod.110.086777
CAS PubMed Web of Science® Google Scholar
43Pangas SA, Li X, Umans L, Zwijsen A, Huylebroeck D, Gutierrez C, et al. Conditional deletion of Smad1 and Smad5 in somatic cells of male and female gonads leads to metastatic tumor development in mice. Mol Cell Biol. 2008; 28: 248–257.
10.1128/MCB.01404-07
CAS PubMed Web of Science® Google Scholar
44Middlebrook BS, Eldin K, Li X, Shivasankaran S, Pangas SA. Smad1-Smad5 ovarian conditional knockout mice develop a disease profile similar to the juvenile form of human granulosa cell tumors. Endocrinology. 2009; 150: 5208–5217.
10.1210/en.2009-0644
CAS PubMed Web of Science® Google Scholar
45Yi SE, LaPolt PS, Yoon BS, Chen JY, Lu JK, Lyons KM. The type I BMP receptor BmprIB is essential for female reproductive function. Proc Natl Acad Sci USA. 2001; 98: 7994–7999.
10.1073/pnas.141002798
CAS PubMed Web of Science® Google Scholar
46Gode F, Gulekli B, Dogan E, Korhan P, Dogan S, Bige O, et al. Influence of follicular fluid GDF9 and BMP15 on embryo quality. Fertil Steril. 2011; 95: 2274–2278.
10.1016/j.fertnstert.2011.03.045
CAS PubMed Web of Science® Google Scholar
47Montgomery GW, Zhao ZZ, Marsh AJ, Mayne R, Treloar SA, James M, et al. A deletion mutation in GDF9 in sisters with spontaneous DZ twins. Twin Res. 2004; 7: 548–555.
10.1375/1369052042663823
PubMed Web of Science® Google Scholar
48Palmer JS, Zhao ZZ, Hoekstra C, Hayward NK, Webb PM, Whiteman DC, et al. Novel variants in growth differentiation factor 9 in mothers of dizygotic twins. J Clin Endocrinol Metab. 2006; 91: 4713–4716.
10.1210/jc.2006-0970
CAS PubMed Web of Science® Google Scholar
49Dixit H, Rao LK, Padmalatha V, Kanakavalli M, Deenadayal M, Gupta N, et al. Mutational screening of the coding region of growth differentiation factor 9 gene in Indian women with ovarian failure. Menopause. 2005; 12: 749–754.
10.1097/01.gme.0000184424.96437.7a
PubMed Web of Science® Google Scholar
50Laissue P, Christin-Maitre S, Touraine P, Kuttenn F, Ritvos O, Aittomaki K, et al. Mutations and sequence variants in GDF9 and BMP15 in patients with premature ovarian failure. Eur J Endocrinol. 2006; 154: 739–744.
10.1530/eje.1.02135
CAS PubMed Web of Science® Google Scholar
51Kovanci E, Rohozinski J, Simpson JL, Heard MJ, Bishop CE, Carson SA. Growth differentiating factor-9 mutations may be associated with premature ovarian failure. Fertil Steril. 2007; 87: 143–146.
10.1016/j.fertnstert.2006.05.079
CAS PubMed Web of Science® Google Scholar
52Zhao H, Qin Y, Kovanci E, Simpson JL, Chen ZJ, Rajkovic A. Analyses of GDF9 mutation in 100 Chinese women with premature ovarian failure. Fertil Steril. 2007; 88: 1474–1476.
10.1016/j.fertnstert.2007.01.021
CAS PubMed Web of Science® Google Scholar
53Di Pasquale E, Beck-Peccoz P, Persani L. Hypergonadotropic ovarian failure associated with an inherited mutation of human bone morphogenetic protein-15 (BMP15) gene. Am J Hum Genet. 2004; 75: 106–111.
10.1086/422103
CAS PubMed Web of Science® Google Scholar
54Dixit H, Rao LK, Padmalatha VV, Kanakavalli M, Deenadayal M, Gupta N, et al. Missense mutations in the BMP15 gene are associated with ovarian failure. Hum Genet. 2006; 119: 408–415.
10.1007/s00439-006-0150-0
CAS PubMed Web of Science® Google Scholar
55Rossetti R, Di Pasquale E, Marozzi A, Bione S, Toniolo D, Grammatico P, et al. BMP15 mutations associated with primary ovarian insufficiency cause a defective production of bioactive protein. Hum Mutat. 2009; 30: 804–810.
10.1002/humu.20961
CAS PubMed Web of Science® Google Scholar
56Wang B, Wen Q, Ni F, Zhou S, Wang J, Cao Y, et al. Analyses of growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) mutation in Chinese women with premature ovarian failure. Clin Endocrinol (Oxf). 2010; 72: 135–136.
10.1111/j.1365-2265.2009.03613.x
CAS PubMed Web of Science® Google Scholar
57Tiotiu D, Alvaro Mercadal B, Imbert R, Verbist J, Demeestere I, De Leener A, et al. Variants of the BMP15 gene in a cohort of patients with premature ovarian failure. Hum Reprod. 2010; 25: 1581–1587.
10.1093/humrep/deq073
CAS PubMed Web of Science® Google Scholar
58Regan SL, Knight PG, Yovich JL, Stanger JD, Leung Y, Arfuso F, et al. Dysregulation of granulosal bone morphogenetic protein receptor 1B density is associated with reduced ovarian reserve and the age-related decline in human fertility. Mol Cell Endocrinol. 2016; 425: 84–93.
10.1016/j.mce.2016.01.016
CAS PubMed Web of Science® Google Scholar
59Peng J, Li Q, Wigglesworth K, Rangarajan A, Kattamuri C, Peterson RT, et al. Growth differentiation factor 9: bone morphogenetic protein 15 heterodimers are potent regulators of ovarian functions. Proc Natl Acad Sci USA. 2013; 110: E776–E785.
10.1073/pnas.1218020110
CAS PubMed Web of Science® Google Scholar
60Stocker WA, Walton KL, Richani D, Chan KL, Beilby KH, Finger BJ, et al. A variant of human growth differentiation factor-9 that improves oocyte developmental competence. J Biol Chem. 2020; 295: 7981–7991.
10.1074/jbc.RA120.013050
CAS PubMed Web of Science® Google Scholar
61Mottershead DG, Sugimura S, Al-Musawi SL, Li JJ, Richani D, White MA, et al. Cumulin, an oocyte-secreted heterodimer of the transforming growth factor-beta family, is a potent activator of granulosa cells and improves oocyte quality. J Biol Chem. 2015; 290: 24007–24020.
10.1074/jbc.M115.671487
CAS PubMed Web of Science® Google Scholar
62Akin N, Richani D, Liao X, Zhao Y, Herta AC, Billooye K, et al. Effect of cumulin and super-GDF9 in standard and biphasic mouse IVM. J Assist Reprod Genet. 2022; 39: 127–140.
10.1007/s10815-021-02382-z
PubMed Web of Science® Google Scholar
63Valve E, Penttila TL, Paranko J, Harkonen P. FGF-8 is expressed during specific phases of rodent oocyte and spermatogonium development. Biochem Biophys Res Commun. 1997; 232: 173–177.
10.1006/bbrc.1997.6256
CAS PubMed Web of Science® Google Scholar
64Buratini J Jr, Teixeira AB, Costa IB, Glapinski VF, Pinto MG, Giometti IC, et al. Expression of fibroblast growth factor-8 and regulation of cognate receptors, fibroblast growth factor receptor-3c and −4, in bovine antral follicles. Reproduction. 2005; 130: 343–350.
10.1530/rep.1.00642
CAS PubMed Web of Science® Google Scholar
65Valve E, Martikainen P, Seppanen J, Oksjoki S, Hinkka S, Anttila L, et al. Expression of fibroblast growth factor (FGF)-8 isoforms and FGF receptors in human ovarian tumors. Int J Cancer. 2000; 88: 718–725.
10.1002/1097-0215(20001201)88:5<718::AID-IJC6>3.0.CO;2-F
CAS PubMed Web of Science® Google Scholar
66Zhong W, Wang QT, Sun T, Wang F, Liu J, Leach R, et al. FGF ligand family mRNA expression profile for mouse preimplantation embryos, early gestation human placenta, and mouse trophoblast stem cells. Mol Reprod Dev. 2006; 73: 540–550.
10.1002/mrd.20417
CAS PubMed Web of Science® Google Scholar
67Machado MF, Caixeta ES, Sudiman J, Gilchrist RB, Thompson JG, Lima PF, et al. Fibroblast growth factor 17 and bone morphogenetic protein 15 enhance cumulus expansion and improve quality of in vitro-produced embryos in cattle. Theriogenology. 2015; 84: 390–398.
10.1016/j.theriogenology.2015.03.031
CAS PubMed Web of Science® Google Scholar
68Portela VM, Machado M, Buratini J Jr, Zamberlam G, Amorim RL, Goncalves P, et al. Expression and function of fibroblast growth factor 18 in the ovarian follicle in cattle. Biol Reprod. 2010; 83: 339–346.
10.1095/biolreprod.110.084277
CAS PubMed Web of Science® Google Scholar
69Asakai R, Song SY, Itoh N, Yamakuni T, Tamura K, Okamoto R. Differential gene expression of fibroblast growth factor receptor isoforms in rat ovary. Mol Cell Endocrinol. 1994; 104: 75–80.
10.1016/0303-7207(94)90053-1
CAS PubMed Web of Science® Google Scholar
70Ben-Haroush A, Abir R, Ao A, Jin S, Kessler-Icekson G, Feldberg D, et al. Expression of basic fibroblast growth factor and its receptors in human ovarian follicles from adults and fetuses. Fertil Steril. 2005; 84(Suppl 2): 1257–1268.
10.1016/j.fertnstert.2005.05.018
CAS PubMed Google Scholar
71Berisha B, Sinowatz F, Schams D. Expression and localization of fibroblast growth factor (FGF) family members during the final growth of bovine ovarian follicles. Mol Reprod Dev. 2004; 67: 162–171.
10.1002/mrd.10386
CAS PubMed Web of Science® Google Scholar
72Puscheck EE, Patel Y, Rappolee DA. Fibroblast growth factor receptor (FGFR)-4, but not FGFR-3 is expressed in the pregnant ovary. Mol Cell Endocrinol. 1997; 132: 169–176.
10.1016/S0303-7207(97)00131-7
CAS PubMed Web of Science® Google Scholar
73Furukawa S, Matsuno Y, Emori C, Fujii W, Naito K, Sugiura K. Expression and regulation of FGF receptors in mouse granulosa cells. J Mamm Ova Res. 2014; 31: 86–92.
10.1274/jmor.31.86
Google Scholar
74Sugiura K, Su YQ, Diaz FJ, Pangas SA, Sharma S, Wigglesworth K, et al. Oocyte-derived BMP15 and FGFs cooperate to promote glycolysis in cumulus cells. Development. 2007; 134: 2593–2603.
10.1242/dev.006882
CAS PubMed Web of Science® Google Scholar
75Sugiura K, Su YQ, Li Q, Wigglesworth K, Matzuk MM, Eppig JJ. Fibroblast growth factors and epidermal growth factor cooperate with oocyte-derived members of the TGFbeta superfamily to regulate Spry2 mRNA levels in mouse cumulus cells. Biol Reprod. 2009; 81: 833–841.
10.1095/biolreprod.109.078485
CAS PubMed Web of Science® Google Scholar
76Miyoshi T, Otsuka F, Yamashita M, Inagaki K, Nakamura E, Tsukamoto N, et al. Functional relationship between fibroblast growth factor-8 and bone morphogenetic proteins in regulating steroidogenesis by rat granulosa cells. Mol Cell Endocrinol. 2010; 325: 84–92.
10.1016/j.mce.2010.04.012
CAS PubMed Web of Science® Google Scholar
77Chen L, Li D, Li C, Engel A, Deng CX. A Ser252Trp [corrected] substitution in mouse fibroblast growth factor receptor 2 (Fgfr2) results in craniosynostosis. Bone. 2003; 33: 169–178.
10.1016/S8756-3282(03)00222-9
CAS PubMed Web of Science® Google Scholar
78Amsterdam A, Kannan K, Givol D, Yoshida Y, Tajima K, Dantes A. Apoptosis of granulosa cells and female infertility in achondroplastic mice expressing mutant fibroblast growth factor receptor 3G374R. Mol Endocrinol. 2001; 15: 1610–1623.
10.1210/mend.15.9.0700
CAS PubMed Google Scholar
79Wang Y, Spatz MK, Kannan K, Hayk H, Avivi A, Gorivodsky M, et al. A mouse model for achondroplasia produced by targeting fibroblast growth factor receptor 3. Proc Natl Acad Sci USA. 1999; 96: 4455–4460.
10.1073/pnas.96.8.4455
CAS PubMed Web of Science® Google Scholar
80Diaz FJ, Wigglesworth K, Eppig JJ. Oocytes determine cumulus cell lineage in mouse ovarian follicles. J Cell Sci. 2007; 120: 1330–1340.
10.1242/jcs.000968
CAS PubMed Web of Science® Google Scholar
81Krege JH, Hodgin JB, Couse JF, Enmark E, Warner M, Mahler JF, et al. Generation and reproductive phenotypes of mice lacking estrogen receptor beta. Proc Natl Acad Sci USA. 1998; 95: 15677–15682.
10.1073/pnas.95.26.15677
CAS PubMed Web of Science® Google Scholar
82Cheng G, Weihua Z, Makinen S, Makela S, Saji S, Warner M, et al. A role for the androgen receptor in follicular atresia of estrogen receptor beta knockout mouse ovary. Biol Reprod. 2002; 66: 77–84.
10.1095/biolreprod66.1.77
CAS PubMed Web of Science® Google Scholar
83Emmen JM, Couse JF, Elmore SA, Yates MM, Kissling GE, Korach KS. In vitro growth and ovulation of follicles from ovaries of estrogen receptor (ER){alpha} and ER{beta} null mice indicate a role for ER{beta} in follicular maturation. Endocrinology. 2005; 146: 2817–2826.
10.1210/en.2004-1108
CAS PubMed Web of Science® Google Scholar
84Couse JF, Yates MM, Deroo BJ, Korach KS. Estrogen receptor-beta is critical to granulosa cell differentiation and the ovulatory response to gonadotropins. Endocrinology. 2005; 146: 3247–3262.
10.1210/en.2005-0213
CAS PubMed Web of Science® Google Scholar
85Couse JF, Hewitt SC, Bunch DO, Sar M, Walker VR, Davis BJ, et al. Postnatal sex reversal of the ovaries in mice lacking estrogen receptors alpha and beta. Science. 1999; 286: 2328–2331.
10.1126/science.286.5448.2328
CAS PubMed Web of Science® Google Scholar
86Sugiura K, Su YQ, Li Q, Wigglesworth K, Matzuk MM, Eppig JJ. Estrogen promotes the development of mouse cumulus cells in coordination with oocyte-derived GDF9 and BMP15. Mol Endocrinol. 2010; 24: 2303–2314.
10.1210/me.2010-0260
CAS PubMed Web of Science® Google Scholar
87Emori C, Wigglesworth K, Fujii W, Naito K, Eppig JJ, Sugiura K. Cooperative effects of 17beta-estradiol and oocyte-derived paracrine factors on the transcriptome of mouse cumulus cells. Endocrinology. 2013; 154: 4859–4872.
10.1210/en.2013-1536
CAS PubMed Web of Science® Google Scholar
88Emori C, Kanke T, Ito H, Akimoto Y, Fujii W, Naito K, et al. Expression and regulation of estrogen receptor 2 and its coregulators in mouse granulosa cells. J Reprod Dev. 2022; 68: 137–143.
10.1262/jrd.2021-114
CAS PubMed Web of Science® Google Scholar
89Wigglesworth K, Lee KB, Emori C, Sugiura K, Eppig JJ. Transcriptomic diversification of developing cumulus and mural granulosa cells in mouse ovarian follicles. Biol Reprod. 2015; 92: 23.
10.1095/biolreprod.114.121756
PubMed Web of Science® Google Scholar
90Emori C, Ito H, Fujii W, Naito K, Sugiura K. Oocytes suppress FOXL2 expression in cumulus cells in mice. Biol Reprod. 2020; 103: 85–93.
10.1093/biolre/ioaa054
PubMed Web of Science® Google Scholar
91Smith MS, Freeman ME, Neill JD. The control of progesterone secretion during the estrous cycle and early pseudopregnancy in the rat: prolactin, gonadotropin and steroid levels associated with rescue of the corpus luteum of pseudopregnancy. Endocrinology. 1975; 96: 219–226.
10.1210/endo-96-1-219
CAS PubMed Web of Science® Google Scholar
92Richards JS. Hormonal control of gene expression in the ovary. Endocr Rev. 1994; 15(6): 725–751.
10.1210/edrv-15-6-725
CAS PubMed Web of Science® Google Scholar
93el-Fouly MA, Cook B, Nekola M, Nalbandov AV. Role of the ovum in follicular luteinization. Endocrinology. 1970; 87: 286–293.
10.1210/endo-87-2-288
CAS PubMed Web of Science® Google Scholar
94Nekola MV, Nalbandov AV. Morphological changes of rat follicular cells as influenced by oocytes. Biol Reprod. 1971; 4: 154–160.
10.1093/biolreprod/4.2.154
CAS PubMed Web of Science® Google Scholar
95Georges A, L'Hote D, Todeschini AL, Auguste A, Legois B, Zider A, et al. The transcription factor FOXL2 mobilizes estrogen signaling to maintain the identity of ovarian granulosa cells. Elife. 2014; 3:e04207.
10.7554/eLife.04207
PubMed Web of Science® Google Scholar
96Schmidt D, Ovitt CE, Anlag K, Fehsenfeld S, Gredsted L, Treier AC, et al. The murine winged-helix transcription factor Foxl2 is required for granulosa cell differentiation and ovary maintenance. Development. 2004; 131: 933–942.
10.1242/dev.00969
CAS PubMed Web of Science® Google Scholar
97Uda M, Ottolenghi C, Crisponi L, Garcia JE, Deiana M, Kimber W, et al. Foxl2 disruption causes mouse ovarian failure by pervasive blockage of follicle development. Hum Mol Genet. 2004; 13: 1171–1181.
10.1093/hmg/ddh124
CAS PubMed Web of Science® Google Scholar
98Uhlenhaut NH, Jakob S, Anlag K, Eisenberger T, Sekido R, Kress J, et al. Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation. Cell. 2009; 139: 1130–1142.
10.1016/j.cell.2009.11.021
CAS PubMed Web of Science® Google Scholar
99Crisponi L, Deiana M, Loi A, Chiappe F, Uda M, Amati P, et al. The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis/ptosis/epicanthus inversus syndrome. Nat Genet. 2001; 27: 159–166.
10.1038/84781
CAS PubMed Web of Science® Google Scholar
100Shah SP, Kobel M, Senz J, Morin RD, Clarke BA, Wiegand KC, et al. Mutation of FOXL2 in granulosa-cell tumors of the ovary. N Engl J Med. 2009; 360(26): 2719–2729.
10.1056/NEJMoa0902542
CAS PubMed Web of Science® Google Scholar
101Jamieson S, Fuller PJ. Molecular pathogenesis of granulosa cell tumors of the ovary. Endocr Rev. 2012; 33: 109–144.
10.1210/er.2011-0014
CAS PubMed Web of Science® Google Scholar
102Ito H, Emori C, Kobayashi M, Maruyama N, Fujii W, Naito K, et al. Cooperative effects of oocytes and estrogen on the forkhead box L2 expression in mural granulosa cells in mice. Sci Rep. 2022; 12: 20158.
10.1038/s41598-022-24680-x
CAS PubMed Web of Science® Google Scholar
103Emori C, Sugiura K. Role of oocyte-derived paracrine factors in follicular development. Anim Sci J. 2014; 85: 627–633.
10.1111/asj.12200
CAS PubMed Web of Science® Google Scholar
104Goldenberg RL, Vaitukaitis JL, Ross GT. Estrogen and follicle stimulation hormone interactions on follicle growth in rats. Endocrinology. 1972; 90: 1492–1498.
10.1210/endo-90-6-1492
CAS PubMed Web of Science® Google Scholar
105Moon YS, Dorrington JH, Armstrong DT. Stimulatory action of follicle-stimulating hormone on estradiol-17 beta secretion by hypophysectomized rat ovaries in organ culture. Endocrinology. 1975; 97: 244–247.
10.1210/endo-97-1-244
CAS PubMed Web of Science® Google Scholar
106Zeleznik AJ, Midgley AR Jr, Reichert LE Jr. Granulosa cell maturation in the rat: increased binding of human chorionic gonadotropin following treatment with follicle-stimulating hormone in vivo. Endocrinology. 1974; 95: 818–825.
10.1210/endo-95-3-818
CAS PubMed Web of Science® Google Scholar
107Paladino G. I ponti intercellulari fra l'uovo ovarico e le cellule follicolari, et la formazione della zona pellucida. Anat Anz. 1890; 15: 254–259.
Google Scholar

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Volume22, Issue1

January/December 2023

e12538

Paracrine regulation of granulosa cell development in the antral follicles in mammals