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The Bone Morphogenetic Protein 15 Gene Is X-Linked and Expressed in Oocytes

Department of Tissue Growth and Repair (J.L.D., A.J.C.) Genetics Institute, Inc. Cambridge, Massachusetts 02140
Departments of Orthopaedic Surgery and Biological Chemistry (K.M.L.) University of California Los Angeles School of Medicine Los Angeles, California 90095
Departments of Pathology (P.W., J.E., M.M.M.), Cell Biology (M.M.M.), and Molecular and Human Genetics (J.E., M.M.M.) Baylor College of Medicine Houston, Texas 77030

	ABSTRACT

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We have taken advantage of the sequence relationships among the bone morphogenetic proteins (BMPs) to identify the mouse Bmp15 and human BMP15 genes. The 392-amino acid prepropeptides encoded by these BMP genes exhibit significant homology to each other, although the 70% identity observed between the 125-amino acid mature peptides is considerably lower than that seen in comparisons of other mouse and human orthologs. Both genes share a common structural organization and encode mature peptides that lack the cysteine residue normally involved in the formation of a covalent dimer. In addition, mouse Bmp15 and human BMP15 map to conserved syntenic regions on the X chromosome. We demonstrate, through a combination of Northern blot and in situ hybridization analyses, that mouse Bmp15 is expressed specifically in the oocyte beginning at the one-layer primary follicle stage and continuing through ovulation. Interestingly, BMP-15 is most closely related to and shares a coincident expression pattern with the mouse growth/differentiation factor 9 (GDF-9) gene that is essential for female fertility. Our findings will be important for defining the role of BMP-15 in follicular development.

	INTRODUCTION

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The transforming growth factor-ß (TGFß) superfamily, which includes the bone morphogenetic proteins (BMPs) and the growth/differentiation factors (GDFs), is the largest family of extracellular signaling proteins yet described. Homology-based cloning approaches have resulted in the identification of TGFß-like factors in such diverse species as Caenorhabditis elegans, Drosophila melanogaster, and Xenopus laevis and have extended the number of mammalian members to more than 30 (1, 2, 3). These molecules, synthesized as prepropeptides and processed into dimeric proteins, are structurally related in their mature, carboxy-terminal region. Members of the BMP subfamily have been shown to be involved in a wide array of cellular processes during embryonic development. For example, BMP-2 and BMP-4 are required for cellular differentiation in early embryogenesis (4, 5), BMP-5 is required for the formation of specific skeletal structures (6), BMP-7 is necessary for normal eye and kidney development (7), and BMP-8a and BMP-8b are essential factors for spermatogenesis (8, 9). BMP subfamily members have also been shown to affect adult tissue repair. Animal models have demonstrated the ability of several BMPs to induce the formation of bone and cartilage (10, 11) and tendon/ligament (12). Identification of new members in this gene family is important for continued characterization of the key factors involved in mammalian development and physiology.

Reproductive development and function are complex processes involving both genetically determined and physiological events. Discerning the role that each of these growth factors plays in vivo would lead to a better understanding of the complex and sex-specific physiology of the mammalian reproductive system. Several members of the TGFß superfamily, such as the inhibins and activins (13), Müllerian inhibiting substance (14), BMP-8a (8), BMP-8b (9), and GDF-9 (15, 16), are implicated as important regulatory factors in mammalian reproduction. For example, we have previously generated mice lacking this oocyte-specific growth factor using embryonic stem cell technology (16) and found that absence of GDF-9 results in an early block in folliculogenesis at the one-layer primary follicle stage leading to infertility. These studies have defined GDF-9 as the first oocyte-derived growth factor required for somatic cell function in vivo.

In the present study, we report the identification of new genes, which we have named bone morphogenetic protein 15 (BMP15 in humans, Bmp15 in mice).¹ Using the sequence relationships of previously characterized BMPs and a degenerate PCR approach, we first identified the mouse gene. To identify the human sequence, low-stringency hybridization with a probe derived from a mouse genomic clone was necessary because the two sequences were unusually divergent. Chromosomal mapping of mouse Bmp15 and human BMP15 has identified them as X-linked genes. In situ hybridization in the mouse has demonstrated that Bmp15 is expressed exclusively in the oocyte soon after primordial follicles are recruited, and expression is maintained until after ovulation. Thus, BMP-15 is the second oocyte-derived growth factor of the TGFß superfamily that may be critical for ovarian function.

	RESULTS

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Identification of the Mouse Bmp15 Gene and cDNA
To identify novel BMP genes, we adopted a PCR approach based on conserved amino acid sequences of the BMP/Vg-1/DPP subgroup of the TGFß superfamily (12). Two consensus mature peptide sequences, WQ/NDWIV/IA and NHAIV/LQT, were used to design degenerate oligonucleotide primers. Based on the relative location of these consensus sequences in other BMPs, we predicted that 128-bp products would be generated by PCR. All products of this size range were subcloned and analyzed for novel BMP-like sequences. A subclone produced by degenerate PCR from mouse genomic DNA, designated mPC-3, contained such a novel sequence. Oligonucleotides derived from this sequence were used to screen a mouse strain 129SvEv genomic library and resulted in the identification of a recombinant phage clone, ø60, which contains sequences identical to that of mPC-3 (Fig. 1A). DNA sequence analysis of ø60 indicated that it contained a segment of a novel gene, which we named mouse Bmp15. Based on homology with other BMP subfamily members, this sequence identifies a single exon that encodes the complete mature domain and part of the propeptide region of BMP-15. A portion of ø60 that contained 508 bp of mouse Bmp15 coding sequence was designated probe 1031 (Fig. 1, A and B).

View larger version (17K): [in this window] [in a new window]   Figure 1. Genomic and cDNA Representations of Mouse Bmp15 and Human BMP15 In each case, diagonally shaded boxes indicate prepropeptide-encoding domains and black boxes indicate mature- encoding domains. A, Shown on the bottom, the structure of the mouse Bmp15 gene as determined by overlapping phage clones and 5'-RACE. The entire protein-coding sequence is contained within two exons, separated by a 3.5-kb intron. 5'- and 3'-UTR sequences (open boxes) indicate the limits of the exons. Probe Pc26–1 is the region used to map the mouse Bmp15 gene. B, Schematic representation of mouse Bmp15 coding sequence and two representative clones isolated from the mouse ovary cDNA library. The signal peptide-encoding sequence is shaded. Probe 1031, which includes a portion of the propeptide- and mature-encoding domains, is shown. C, Structure of the human BMP15 gene. The entire protein-coding sequence is contained within two exons (shown with boxes), separated by a 4.2-kb intron. A 3-kb EcoRI fragment encoding part of the propeptide domain and the entire mature domain was used for chromosomal localization by FISH. B, BamHI; RI, EcoRI; RV, EcoRV; K, KpnI.

Probe 1031 was used to rescreen the mouse genomic library and identified several overlapping recombinant phage clones including PW-8 and PW-9 (Fig. 1A). Restriction endonuclease digestion, Southern blot hybridization, and DNA sequence analysis of PW-8, PW-9, and ø60 were used to determine the structure of the mouse Bmp15 gene. Two exons, separated by a 3.5-kb intron, encode the entire mouse BMP-15 protein. The first exon encodes a 17-amino acid signal peptide (as predicted with the aid of the GeneWorks computer program, Oxford Molecular Groups, Inc., Oxford, England) and part of the propeptide domain. The second exon encodes the remaining propeptide region and the entire predicted 125-amino acid mature domain (Fig. 1, A and B).

Identification of the Human BMP15 Gene
A portion of the ø60 mouse clone was used to screen a human genomic library under reduced stringency conditions. Two hybridizing clones, JLDc1 and JLDc19, were characterized by DNA sequence analysis. Clone JLDc19 contained the complete coding sequence of human BMP15. The genomic structure of human BMP15 was determined by restriction endonuclease digestion, Southern blot hybridization, and DNA sequence analysis. The 1176-bp coding region is contained within two exons separated by 4.2 kb of intervening sequence: the first exon encodes a predicted secretory leader sequence of 17 amino acids followed by 97 amino acids of the propeptide domain; the second exon encodes the remaining 158 amino acids of the propeptide domain and the entire predicted 125-amino acid mature domain (Fig. 1C).

Comparison of Mouse and Human BMP-15
Both mouse and human BMP-15 are encoded by two exons separated by a single intron. Cleavage at the predicted proteolytic processing sites (21, 22), Arg-Ser-Val-Arg in mouse or Arg-Arg-Thr-Arg in human BMP-15, produces 125-amino acid peptides. The prepropeptides (392 amino acids) exhibit an overall identity of 63% (76% at the nucleotide level), while the amino acid identities in the mature domain and propeptide domains are 77% (81% nucleotide identity) and 60% (74% nucleotide identity), respectively (Fig. 2). There are five potential N-linked glycosylation sites in the mouse and human BMP-15 proteins. Three of the sites are spatially conserved between the two species. Both mouse and human BMP-15 contain only six out of the seven cysteine residues observed in the vast majority of proteins in the TGFß superfamily. Interestingly, the mouse and human gene products differ in that mouse BMP-15 has two additional cysteines upstream from the first conserved cysteine, a spatial pattern more characteristic of TGFßs and activins.

View larger version (64K): [in this window] [in a new window]   Figure 2. Deduced Amino Acid Sequence of Mouse (M, top) and Human (H, bottom) BMP-15 The proteolytic processing sites are boxed, and the arrow indicates the predicted start of the mature peptides. The triangles indicate the positions of the single intron in the corresponding genomic DNA sequences. Potential N-linked glycosylation sites are in bold. Cysteine residues characteristic of TGFß superfamily members are boxed and shaded; the cysteine residue thought to be involved in intermolecular bonding is replaced by a serine residue and is boxed. Two additional cysteines present in the N-terminal region of the mouse BMP-15 mature peptide are underlined. Note also the sequence divergence in the mature peptide before the first conserved cysteine.

View larger version (64K): [in this window] [in a new window]   Figure 3. Northern Blot Analysis of Mouse Total RNA from Various Tissues A mouse Bmp15 probe, generated from coding sequence, detected a signal of approximately 3.5 kb in RNA derived from ovary but no other tissue (top). 18S rRNA (bottom) was used as a control for RNA loading.

View larger version (155K): [in this window] [in a new window]   Figure 4. In Situ Hybridization Analysis of Bmp15 mRNA in Mouse Ovaries Brightfield/darkfield (A and C) or darkfield (B and D) analysis of Bmp15 mRNA in adult wild-type ovaries. Similar to Gdf9 (Ref. 15 and our unpublished data), Bmp15 is absent in primordial and small type 3a follicles (solid arrow, C and D) but is expressed in oocytes of larger type 3a, type 3b, and type 4 follicles (open arrow, C and D) and oocytes of all later stage follicles including antral (a) follicles (A and B).

View larger version (41K): [in this window] [in a new window]   Figure 5. Chromosomal Localization of Mouse Bmp15 and Human BMP15 Genes A, Bmp15 maps to the proximal region of the mouse X chromosome. Using the Jackson Laboratory interspecific backcross panels (C57BL/6JEi x SPRET/Ei)F1 x SPRET/Ei), the mouse Bmp15 locus was placed adjacent to the centromere on the X chromosome. The segregation of Bmp15 and flanking genes in 94 backcross mice typed for all loci are shown at the top of the figure. Black and white boxes indicate C57BL/6JEi and SPRET/Ei alleles, respectively. Numbers at the bottom of each column represent the number of backcross progeny that has inherited a recombinant or nonrecombinant chromosome from the (C57BL/6JEi x SPRET/Ei)F1 parent. Note that one mouse has placed Bmp15 and DXMit26 proximal to Pmv1 and the more distal markers. A partial linkage map of the proximal X chromosome is shown below. B, BMP15 maps to the human X chromosome by FISH. The arrow indicates the hybridization signals of twin dots on the human X chromosome. Based on analysis of metaphase chromosomes isolated from a male, the human BMP15 gene was localized to Xp11.2.

	DISCUSSION

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View larger version (26K): [in this window] [in a new window]   Figure 6. Dendogram of the TGF-ß Superfamily and Comparisons of BMP-15 and GDF-9 A, The relationship of BMP15 to other members of the TGFß superfamily. The figure was generated using the cysteine-rich COOH-terminal polypeptides of the TGFß superfamily members, which were aligned using the PILEUP program (Genetics Computer Group, Madison, WI). B, The BMP-15/GDF-9 subfamily. Percent amino acid identities are indicated and were generated as described above.

Several members of the TGFß superfamily have been demonstrated to exist naturally as heterodimers and in some cases have different activities than their homodimeric counterparts (13, 31). The inhibins, which inhibit FSH release from the pituitary (32), have not been shown to exist in homodimeric form but, rather, they are examples of functional heterodimers of two distinct TGFß superfamily members, inhibin and activin ßA or ßB. Recombinant heterodimers between the BMP-2/4 subgroup and the BMP-5/6/7 subgroup have also been shown to exhibit a significant increase in biological activity when compared with homodimers assayed in the same system (33, 34, 35). With these BMPs, increased levels of homodimers can match the activity of heterodimers in these systems.

Female infertility in GDF-9-deficient mice is the result of arrested follicular development at the primary follicle (type 3B) stage. This block in folliculogenesis approximates the onset of expression of Gdf9 and Bmp15, which are both detected in oocytes of one-layer primary (type 3A) follicles and remain highly expressed in the oocyte throughout the course of follicular maturation and ovulation. Interestingly, GDF-9-deficient mice continue to synthesize Bmp15 mRNA (our unpublished data). Thus, based on their coincident expression pattern, one potential explanation for the lack of phenotypic rescue by BMP-15 of the GDF-9-deficient mice is that BMP-15 and GDF-9 are capable of forming heterodimers, and it is the heterodimeric form, BMP-15/GDF-9, which supports follicular maturation. Alternatively, BMP-15 and GDF-9 may only form homodimers with distinct biological functions. Ongoing studies to generate Bmp15 knockout mice may elucidate whether BMP-15 and GDF-9 form active heterodimers in vivo and will help us to further define their roles in reproductive physiology.

	MATERIALS AND METHODS

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Degenerate PCR
The oligonucleotides 5'-gcggatccTGG(C/A)ANGA(C/T)TG-GAT(A/C/T)(G/A)TNGCN and 5'-gctctagaGT(C/T)TGNA (C/T)NATNGC(A/G)TG(A/G)TT-3' were used for PCR on mouse genomic DNA to amplify BMP-related sequences as previously described (12). The lowercase letters include recognition sequences for the restriction endonucleases BamHI and XbaI, respectively, which were added to facilitate the subcloning of the expected 128-bp PCR products into pGEM-3 (Promega, Madison, WI).

Genomic Library Screening
The oligonucleotides 5'-TCCTCGTCTCTATACCCCAAAT-TACTGTAAGGAATCTGT-3' and 5'-ATCTGTACTCGGGTATTACCCTATGGTCTCAATTCACCC-3' were kinased with [³²P]-ATP and hybridized to duplicate nitrocellulose replicas of 500,000 recombinants of a mouse genomic library (no. 946309, Stratagene, La Jolla, CA) in standard hybridization buffer (SHB = 5xSSC/5x Denhardt’s solution/0.1% SDS/100 µg denatured salmon sperm DNA) at 60 C overnight. The filters were washed extensively with 5x SSC/0.1% SDS at 60 C and subjected to autoradiography for 2 days at -80 C with intensifying screens. An additional 600,000 recombinants of this same mouse genomic library were screened. Duplicate nitrocellulose filters were hybridized to a DNA fragment of genomic clone ø60 corresponding to nucleotides 1139–1418 of the mouse Bmp15 sequence, hereafter designated probe 1031. This probe was random primed with [-³²P]dCTP and hybridized to nitrocellulose filters in Church’s solution [0.5 M sodium phosphate buffer (pH 5.2)/7.5% SDS] at 63 C. Filters were washed with 0.1x Church’s solution and exposed overnight at -80 C. Approximately 1,000,000 recombinants of a human genomic library (Stratagene no. 945203) were screened with [-³²P]dCTP random-primed mouse probe 1031 at 60 C in SHB overnight. Duplicate nitrocellulose filters were washed with 2x SSC/0.1% SDS at 60 C and exposed for 2 days at -80 C with intensifying screens.

mRNA Isolation and cDNA Library Construction
Total RNA was extracted from various tissues of adult Swiss Webster mice or C57BL/6/129SvEv hybrid mice using RNA STAT-60 (Leedo Medical Laboratories, Houston, TX) as described by the manufacturer. Poly (A)⁺ RNA was purified using Oligotex-d7 beads (Qiagen, Chatsworth, CA) according to the manufacturer’s instructions. Mouse ovarian mRNA was used to construct a directional (5'-EcoRI to 3'-XhoI), oligo (dT)-primed cDNA library in the bacteriophage vector ZAP Express using the ZAP Express cDNA cloning kit (Stratagene).

Northern Blot Hybridization
Total RNA (12 µg) derived from multiple mouse tissues was electrophoresed on a 1.2% agarose/7.6% formaldehyde gel and transferred to Hybond-N (Amersham, Arlington Heights, IL) nylon membrane. Probe 1031 was random primed with [-³²P]dCTP. The membrane was hybridized, washed, and subjected to autoradiography as described (17). An 18S ribosomal RNA cDNA probe was used for the loading control.

cDNA Library Screening and 5'-RACE
Approximately 400,000 clones of the mouse ovarian cDNA library were hybridized to [-³²P]dCTP random-primed probe 1031 in Church’s solution at 63 C. Filters were washed with 0.1x Church’s solution and exposed overnight at -80 C. 5'-RACE PCR was performed using the Marathon cDNA amplification kit (CLONTECH, Palo Alto, CA) under conditions described by the manufacturer. The oligonucleotides used for the amplification were: 5'-GGAAAGTCCAGGGTCTGTACATGCCA-3' and 5'-CCATTGCTTCATCTCTCCTTGCCA-3'.

In Situ Hybridization
In situ hybridization was performed as described previously (18). In brief, freshly dissected ovaries from C57Bl/6/129SvEv hybrid mice were fixed in 4% paraformaldehyde-PBS overnight, processed, embedded in paraffin, and cut to a 5 µm thickness. Mouse Bmp15 probe 1031 antisense and sense strands were generated by labeling with [-³⁵S]UTP using Riboprobe T7/SP6 Combination System (Promega). Hybridization was carried out at 50–55 C with 5 x 10⁶ cpm of each riboprobe per slide for 16 h in 50% deionized formamide/0.3 M NaCl/20 mM Tris-HCl (pH 8.0)/5 mM EDTA/10 mM NaPO₄ (pH 8.0)/10% Dextran sulfate/1x Denhardt’s/0.5 mg/ml yeast RNA. High-stringency washes were carried out in 2x SSC/50% formamide and 0.1x SSC at 65 C. Dehydrated sections were dipped in NTB-2 emulsion (Eastman Kodak, Rochester, NY) and exposed for 4–7 days at 4 C. After the slides were developed and fixed, they were stained with hematoxylin and mounted for photography.

Chromosomal Mapping
Chromosomal localization of the mouse Bmp15 gene was performed using the Jackson Laboratory Interspecific backcross DNA panel (19) using Pc26–1 probe located in the 3'-UTR of the mouse Bmp15 gene. A 3-kb EcoRI fragment from a human BMP15 genomic clone containing a portion of exon 2 and some intron sequence was used to chromosomally map the human BMP15 gene by FISH as described (20). FISH was performed by Dr. Antonio Baldini and the FISH core in the Department of Molecular and Human Genetics at Baylor College of Medicine.

	ACKNOWLEDGMENTS

 
We would like to acknowledge Ms. Susan Benard for DNA sequencing, Dr. Antonio Baldini and the FISH core in the Department of Molecular and Human Genetics at Baylor College of Medicine for mapping the human BMP15 gene, and Drs. Rajendra Kumar, Vicki Rosen, and Gary Hattersley for critical review of the manuscript. The original identification of the Bmp15 subclone mPC-3 by degenerate PCR was performed by K.M.L. in Dr. Brigid Hogan’s laboratory at Vanderbilt University. The PCR conditions for the identification of mPC-3 were optimized by Dr. Gerald Thomsen while in the laboratory of Dr. Doug Melton, Harvard University.

	FOOTNOTES

 
Address requests for reprints to: Martin M. Matzuk, M.D., Ph.D., Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030. E-mail: mmatzuk{at}bcm.tmc.edu

These studies were supported by a sponsored research grant from Genetics Institute and NIH Center Grant HD-07495 (to M.M.M.). Ms. Julia Elvin is a student in the Medical Scientist Training Program supported by NIH Grant GM-08307.

¹ The mouse Bmp15 cDNA and human BMP15 gene sequences in this manuscript have been deposited in GENBANK under the accession numbers AF082348, AF082349, and AF082350.

Received for publication June 17, 1998. Revision received August 19, 1998. Accepted for publication August 31, 1998.

	REFERENCES

TOP ABSTRACT INTRODUCTION RESULTS DISCUSSION MATERIALS AND METHODS REFERENCES

 

1. Hogan BLM 1996 Bone morphogenetic proteins: multifunctional regulators of vertebrate development. Genes Dev 10:1580–1594[Free Full Text]
2. Rosen V, Cox K, Hattersley G 1996 In: Bilezikian JP, Raisz LG, Rodan GA (eds) Principles of Bone Biology. Academic Press, Inc., New York, pp 661–671
3. Kingsley DM 1994 The TGF-beta superfamily: new members, new receptors, and new genetic tests of function in different organisms. Genes Dev 8:133–146[Free Full Text]
4. Zhang H, Bradley A 1996 Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development. Development 122:2977–2986[Abstract]
5. Winnier G, Blessing M, Labosky PA, Hogan BLM 1995 Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev 9:2105–2116[Abstract/Free Full Text]
6. Kingsley DM, Bland AE, Grubber JM, Marker PC, Russell LB, Copeland NG, Jenkins NA 1992 The mouse short ear skeletal morphogenesis locus is associated with defects in a bone morphogenetic member of the TGF beta superfamily. Cell 71:399–410[CrossRef][Medline]
7. Dudley AT, Lyons KM, Robertson EJ 1995 A requirement for bone morphogenetic protein-7 during development of the mammalian kidney and eye. Genes Dev 9:2795–2807[Abstract/Free Full Text]
8. Zhao G-Q, Liaw L, Hogan BLM 1998 Bone morphogenetic protein 8A plays a role in the maintenance of spermatogenesis and the integrity of the epididymis. Development 125:1103–1112[Abstract]
9. Zhao G-Q, Deng K, Labosky PA, Liaw L, Hogan BLM 1996 The gene encoding bone morphogenetic protein 8B is required for the initiation and maintenance of spermatogenesis in the mouse. Genes Dev 10:1657–1669[Abstract/Free Full Text]
10. Wang EA, Rosen V, D’Alessandro JS, Bauduy M, Cordes P, Harada T, Israel D, Hewick R, Kerns K, LaPan P, Luxenberg DP, McQuaid D, Moutsatsos IK, Nove J, Wozney JM 1990 Recombinant human bone morphogenetic protein induces bone formation. Proc Natl Acad Sci USA 87:2220–2224[Abstract/Free Full Text]
11. Sampath TK, Maliakal JC, Hauschka PV, Jones WK, Sasak H, Tucker RF, White KH, Coughlin JE, Tucker MM, Pang RHL, Corbett C, Özkaynak E, Oppermann H, Rueger DC 1992 Recombinant human osteogenic protein-1 (hOP-1) induces new bone formation in vivo with a specific activity comparable with natural bovine osteogenic protein and stimulates osteoblast proliferation and differentiation in vitro. J Biol Chem 267:20352–20362[Abstract/Free Full Text]
12. Wolfman NM, Hattersley G, Cox KA, Celeste AJ, Nelson R, Yamaji N, Dube JL, DiBlasio-Smith E, Nove J, Song JJ, Wozney JM, Rosen V 1997 Ectopic induction of tendon and ligament in rats by growth and differentiation factors 5, 6, and 7, members of the TGF-beta gene family. J Clin Invest 100:321–330[Medline]
13. Lau AL, Shou W, Guo Q, Matzuk MM 1997 Transgenic approaches to study the functions of the transforming growth factor ß superfamily members. In: Aono T, Sugino H, Vale WW (eds) Inhibin, Activin, and Follistatin: Regulatory Functions in System and Cell Biology. Springer-Verlag, New York, Inc., pp 220–243
14. Behringer RR, Finegold MJ, Cate RL 1994 Mullerian-inhibiting substance function during mammalian sexual development. Cell 79:415–425[CrossRef][Medline]
15. McGrath SA, Esquela AF, Lee S-J 1995 Oocyte-specific expression of growth/differentiation factor-9. Mol Endocrinol 9:131–136[Abstract/Free Full Text]
16. Dong J, Albertini DF, Nishimori K, Kumar TR, Lu N, Matzuk MM 1996 Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature 383:531–535[CrossRef][Medline]
17. Mahmoudi M, Lin VK 1989 Comparison of two different hybridization systems in northern transfer analysis. Biotechniques 7:331–332[Medline]
18. Albrecht U, Eichele G, Helms JA, Lu HC 1997 Visualization of gene expression patterns by in situ hybridization. In: Daston GP (ed) Molecular and Cellular Methods in Developmental Toxicology. CRC Press, Boca Raton, FL, pp. 23–48
19. Rowe LB, Nadeau JH, Turner R, Frankel WN, Letts VA, Eppig JT, Ko MS, Thurston SJ, Birkenmeier EH 1994 Maps from two interspecific backcross DNA panels available as a community genetic mapping resource. Mamm Genome 5:253–274[CrossRef][Medline]
20. Baldini A, Ross M, Nizetic D, Vatcheva R, Lindsay EA, Lehrach H, Siniscalo M 1992 Chromosomal assignment of human YAC clones by fluorescence in situ hybridization: use of single-yeast-colony PCR and multiple labeling. Genomics 14:181–184[CrossRef][Medline]
21. Celeste AJ, Iannazzi JA, Taylor RC, Hewick RM, Rosen V, Wang EA, Wozney JM 1990 Identification of transforming growth factor beta family members present in bone-inductive protein purified from bovine bone. Proc Natl Acad Sci USA 87:9843–9847[Abstract/Free Full Text]
22. Özkaynak E, Schnegelsberg PNJ, Jin DF, Clifford GM, Warren FD, Drier EA, Oppermann H 1992 Osteogenic protein-2. A new member of the transforming growth factor-beta superfamily expressed early in embryogenesis. J Biol Chem 267:25220–25227[Abstract/Free Full Text]
23. Pedersen I, Peters HJ 1968 Proposal for a classification of oocytes and follicles in the mouse ovary. J Reprod Fertil 17:555–557[Abstract/Free Full Text]
24. Boyd Y, Herman GE, Avner P, Disteche CM, Adler D, Reed V, Blair HJ 1997 Mouse x Chromosome. Mamm Genome 7:313–326
25. Tatusov RL, Koonin EV, Lipman DJ 1997 A genomic perspective on protein families. Science 278:631–637[Abstract/Free Full Text]
26. Jones CM, Simon-Chazottes D, Guenet J-L, Hogan BLM 1992 Isolation of Vgr-2, a novel member of the transforming growth factor-beta-related gene family. Mol Endocrinol 6:1961–1968[Abstract/Free Full Text]
27. McPherron AC, Lee S-J 1993 GDF-3 and GDF-9: two new members of the transforming growth factor-beta superfamily containing a novel pattern of cysteines. J Biol Chem 268:3444–3449[Abstract/Free Full Text]
28. Daopin S, Piez KA, Ogawa Y, Davies DR 1992 Crystal structure of transforming growth factor-beta 2: an unusual fold for the superfamily. Science 257:369–373[Abstract/Free Full Text]
29. Schlunegger MP, Grütter MG 1993 Refined crystal structure of human transforming growth factor beta 2 at 1.95 A resolution. J Mol Biol 231:445–458[CrossRef][Medline]
30. Griffith DL, Keck PC, Sampath TK, Rueger DC, Carlson WD 1996 Three-dimensional structure of recombinant human osteogenic protein 1: structural paradigm for the transforming growth factor beta superfamily. Proc Natl Acad Sci USA 93:878–883[Abstract/Free Full Text]
31. Cheifetz S, Bassols A, Stanley K, Ohta M, Greenberger J, Massagué J 1988 Heterodimeric transforming growth factor beta. Biological properties and interaction with three types of cell surface receptors. J Biol Chem 263:10783–10789[Abstract/Free Full Text]
32. Mather JP, Moore A, Li RH 1997 Activins, inhibins, and follistatins: further thoughts on a growing family of regulators. Proc Soc Exp Biol Med 215:209–222[CrossRef][Medline]
33. Israel DI, Nove J, Kerns KM, Kaufman RJ, Rosen V, Cox KA, Wozney JM 1996 Heterodimeric bone morphogenetic proteins show enhanced activity in vitro and in vivo. Growth Factors 13:291–300[Medline]
34. Aono A, Hazama M, Notoya K, Taketomi S, Yamasaki H, Tsukuda R, Saski S, Fujisawa Y 1995 Potent ectopic bone-inducing activity of bone morphogenetic protein-4/7 heterodimer. Biochem Biophys Res Commun 210:670–677[CrossRef][Medline]
35. Kusumoto K, Bessho K, Fujimura K, Akioka J, Ogawa Y, Iizuka T 1997 Comparison of ectopic osteoinduction in vivo by recombinant human BMP-2 and recombinant Xenopus BMP-4/7 heterodimer. Biochem Biophys Res Commun 239:575–579[CrossRef][Medline]

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				F. Paradis, S. Novak, G. K Murdoch, M. K Dyck, W. T Dixon, and G. R Foxcroft Temporal regulation of BMP2, BMP6, BMP15, GDF9, BMPR1A, BMPR1B, BMPR2 and TGFBR1 mRNA expression in the oocyte, granulosa and theca cells of developing preovulatory follicles in the pig Reproduction, July 1, 2009; 138(1): 115 - 129. [Abstract] [Full Text] [PDF]

				S. A Williams and P. Stanley Oocyte-specific deletion of complex and hybrid N-glycans leads to defects in preovulatory follicle and cumulus mass development Reproduction, February 1, 2009; 137(2): 321 - 331. [Abstract] [Full Text] [PDF]

				Y. Choi, D. Yuan, and A. Rajkovic Germ Cell-Specific Transcriptional Regulator Sohlh2 Is Essential for Early Mouse Folliculogenesis and Oocyte-Specific Gene Expression Biol Reprod, December 1, 2008; 79(6): 1176 - 1182. [Abstract] [Full Text] [PDF]

				J C Sadeu, T Adriaenssens, and J Smitz Expression of growth differentiation factor 9, bone morphogenetic protein 15, and anti-Mullerian hormone in cultured mouse primary follicles Reproduction, August 1, 2008; 136(2): 195 - 203. [Abstract] [Full Text] [PDF]

				S. A. Williams and P. Stanley Mouse fertility is enhanced by oocyte-specific loss of core 1-derived O-glycans FASEB J, July 1, 2008; 22(7): 2273 - 2284. [Abstract] [Full Text] [PDF]

				H. E. McMahon, O. Hashimoto, P. L. Mellon, and S. Shimasaki Oocyte-Specific Overexpression of Mouse Bone Morphogenetic Protein-15 Leads to Accelerated Folliculogenesis and an Early Onset of Acyclicity in Transgenic Mice Endocrinology, June 1, 2008; 149(6): 2807 - 2815. [Abstract] [Full Text] [PDF]

				E. S. Clelland, Q. Tan, A. Balofsky, R. Lacivita, and C. Peng Inhibition of Premature Oocyte Maturation: A Role for Bone Morphogenetic Protein 15 in Zebrafish Ovarian Follicles Endocrinology, November 1, 2007; 148(11): 5451 - 5458. [Abstract] [Full Text] [PDF]

				T. D. Gallardo, G. B. John, L. Shirley, C. M. Contreras, E. A. Akbay, J. M. Haynie, S. E. Ward, M. J. Shidler, and D. H. Castrillon Genomewide Discovery and Classification of Candidate Ovarian Fertility Genes in the Mouse Genetics, September 1, 2007; 177(1): 179 - 194. [Abstract] [Full Text] [PDF]

				E. Nilsson, N. Rogers, and M. K Skinner Actions of anti-Mullerian hormone on the ovarian transcriptome to inhibit primordial to primary follicle transition Reproduction, August 1, 2007; 134(2): 209 - 221. [Abstract] [Full Text] [PDF]

				Y.-T. Wu, L. Tang, J. Cai, X.-E Lu, J. Xu, X.-M. Zhu, Q. Luo, and H.-F. Huang High bone morphogenetic protein-15 level in follicular fluid is associated with high quality oocyte and subsequent embryonic development Hum. Reprod., June 1, 2007; 22(6): 1526 - 1531. [Abstract] [Full Text] [PDF]

				L. S. Sleer and C. C. Taylor Cell-Type Localization of Platelet-Derived Growth Factors and Receptors in the Postnatal Rat Ovary and Follicle Biol Reprod, March 1, 2007; 76(3): 379 - 390. [Abstract] [Full Text] [PDF]

				L. Liu and W. Ge Growth Differentiation Factor 9 and Its Spatiotemporal Expression and Regulation in the Zebrafish Ovary Biol Reprod, February 1, 2007; 76(2): 294 - 302. [Abstract] [Full Text] [PDF]

				L. Bodin, E. Di Pasquale, S. Fabre, M. Bontoux, P. Monget, L. Persani, and P. Mulsant A Novel Mutation in the Bone Morphogenetic Protein 15 Gene Causing Defective Protein Secretion Is Associated with Both Increased Ovulation Rate and Sterility in Lacaune Sheep Endocrinology, January 1, 2007; 148(1): 393 - 400. [Abstract] [Full Text] [PDF]

				P. Y. Fechner, M. L. Davenport, R. L. Qualy, J. L. Ross, D. F. Gunther, E. A. Eugster, C. Huseman, A. J. Zagar, C. A. Quigley, and on behalf of the Toddler Turner Study Group Differences in Follicle-Stimulating Hormone Secretion between 45,X Monosomy Turner Syndrome and 45,X/46,XX Mosaicism Are Evident at an Early Age J. Clin. Endocrinol. Metab., December 1, 2006; 91(12): 4896 - 4902. [Abstract] [Full Text] [PDF]

				X. Gueripel, V. Brun, and A. Gougeon Oocyte Bone Morphogenetic Protein 15, but not Growth Differentiation Factor 9, Is Increased During Gonadotropin-Induced Follicular Development in the Immature Mouse and Is Associated with Cumulus Oophorus Expansion Biol Reprod, December 1, 2006; 75(6): 836 - 843. [Abstract] [Full Text] [PDF]

				Y. Choi and A. Rajkovic Characterization of NOBOX DNA Binding Specificity and Its Regulation of Gdf9 and Pou5f1 Promoters J. Biol. Chem., November 24, 2006; 281(47): 35747 - 35756. [Abstract] [Full Text] [PDF]

				K. F. Rodriguez, L. A. Blomberg, K. A. Zuelke, J. R. Miles, J. E. Alexander, and C. E. Farin Identification of candidate mRNAs associated with gonadotropin-induced maturation of murine cumulus oocyte complexes using serial analysis of gene expression Physiol Genomics, November 21, 2006; 27(3): 318 - 327. [Abstract] [Full Text] [PDF]

				P. Laissue, S. Christin-Maitre, P. Touraine, F. Kuttenn, O. Ritvos, K. Aittomaki, N. Bourcigaux, L. Jacquesson, P. Bouchard, R. Frydman, et al. Mutations and sequence variants in GDF9 and BMP15 in patients with premature ovarian failure. Eur. J. Endocrinol., May 1, 2006; 154(5): 739 - 744. [Abstract] [Full Text] [PDF]

				E. Di Pasquale, R. Rossetti, A. Marozzi, B. Bodega, S. Borgato, L. Cavallo, S. Einaudi, G. Radetti, G. Russo, M. Sacco, et al. Identification of New Variants of Human BMP15 Gene in a Large Cohort of Women with Premature Ovarian Failure J. Clin. Endocrinol. Metab., May 1, 2006; 91(5): 1976 - 1979. [Abstract] [Full Text] [PDF]

				B. K. Campbell, C. J. H. Souza, A. J. Skinner, R. Webb, and D. T. Baird Enhanced Response of Granulosa and Theca Cells from Sheep Carriers of the FecB Mutation in Vitro to Gonadotropins and Bone Morphogenic Protein-2, -4, and -6 Endocrinology, April 1, 2006; 147(4): 1608 - 1620. [Abstract] [Full Text] [PDF]

				E. Clelland, G. Kohli, R. K. Campbell, S. Sharma, S. Shimasaki, and C. Peng Bone Morphogenetic Protein-15 in the Zebrafish Ovary: Complementary Deoxyribonucleic Acid Cloning, Genomic Organization, Tissue Distribution, and Role in Oocyte Maturation Endocrinology, January 1, 2006; 147(1): 201 - 209. [Abstract] [Full Text] [PDF]

				S. A. Pangas and M. M. Matzuk The Art and Artifact of GDF9 Activity: Cumulus Expansion and the Cumulus Expansion-Enabling Factor Biol Reprod, October 1, 2005; 73(4): 582 - 585. [Abstract] [Full Text] [PDF]

				M. K. Skinner Regulation of primordial follicle assembly and development Hum. Reprod. Update, September 1, 2005; 11(5): 461 - 471. [Abstract] [Full Text] [PDF]

				D. Goswami and G. S. Conway Premature ovarian failure Hum. Reprod. Update, July 1, 2005; 11(4): 391 - 410. [Abstract] [Full Text] [PDF]

				M. Vallee, C. Gravel, M.-F. Palin, H. Reghenas, P. Stothard, D. S. Wishart, and M.-A. Sirard Identification of Novel and Known Oocyte-Specific Genes Using Complementary DNA Subtraction and Microarray Analysis in Three Different Species Biol Reprod, July 1, 2005; 73(1): 63 - 71. [Abstract] [Full Text] [PDF]

				O. Hashimoto, R. K. Moore, and S. Shimasaki Posttranslational processing of mouse and human BMP-15: Potential implication in the determination of ovulation quota PNAS, April 12, 2005; 102(15): 5426 - 5431. [Abstract] [Full Text] [PDF]

				J. D. Hennebold, K. Mah, W. Perez, J. E. Vance, R. L. Stouffer, C. Morisseau, B. D. Hammock, and E. Y. Adashi Identification and Characterization of an Ovary-Selective Isoform of Epoxide Hydrolase Biol Reprod, April 1, 2005; 72(4): 968 - 975. [Abstract] [Full Text] [PDF]

				J.L. Juengel and K.P. McNatty The role of proteins of the transforming growth factor-{beta} superfamily in the intraovarian regulation of follicular development Hum. Reprod. Update, March 1, 2005; 11(2): 144 - 161. [Abstract] [Full Text] [PDF]

				F. H. Thomas, J.-F. Ethier, S. Shimasaki, and B. C. Vanderhyden Follicle-Stimulating Hormone Regulates Oocyte Growth by Modulation of Expression of Oocyte and Granulosa Cell Factors Endocrinology, February 1, 2005; 146(2): 941 - 949. [Abstract] [Full Text] [PDF]

				N. Kaivo-Oja, D. G. Mottershead, S. Mazerbourg, S. Myllymaa, S. Duprat, R. B. Gilchrist, N. P. Groome, A. J. Hsueh, and O. Ritvos Adenoviral Gene Transfer Allows Smad-Responsive Gene Promoter Analyses and Delineation of Type I Receptor Usage of Transforming Growth Factor-{beta} Family Ligands in Cultured Human Granulosa Luteal Cells J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 271 - 278. [Abstract] [Full Text] [PDF]

				S. Pennetier, S. Uzbekova, C. Perreau, P. Papillier, P. Mermillod, and R. Dalbies-Tran Spatio-Temporal Expression of the Germ Cell Marker Genes MATER, ZAR1, GDF9, BMP15,andVASA in Adult Bovine Tissues, Oocytes, and Preimplantation Embryos Biol Reprod, October 1, 2004; 71(4): 1359 - 1366. [Abstract] [Full Text] [PDF]

				M. Matsui, B. Sonntag, S. S. Hwang, T. Byerly, A. Hourvitz, E. Y. Adashi, S. Shimasaki, and G. F. Erickson Pregnancy-Associated Plasma Protein-A Production in Rat Granulosa Cells: Stimulation by Follicle-Stimulating Hormone and Inhibition by the Oocyte-Derived Bone Morphogenetic Protein-15 Endocrinology, August 1, 2004; 145(8): 3686 - 3695. [Abstract] [Full Text] [PDF]

				K. Bogner, K.-D. Hinsch, P. Nayudu, L. Konrad, C. Cassara, and E. Hinsch Localization and synthesis of zona pellucida proteins in the marmoset monkey (Callithrix jacchus) ovary Mol. Hum. Reprod., July 1, 2004; 10(7): 481 - 488. [Abstract] [Full Text] [PDF]

				J. D. Hennebold Characterization of the ovarian transcriptome through the use of differential analysis of gene expression methodologies Hum. Reprod. Update, May 1, 2004; 10(3): 227 - 239. [Abstract] [Full Text] [PDF]

				W. X. Liao, R. K. Moore, and S. Shimasaki Functional and Molecular Characterization of Naturally Occurring Mutations in the Oocyte-secreted Factors Bone Morphogenetic Protein-15 and Growth and Differentiation Factor-9 J. Biol. Chem., April 23, 2004; 279(17): 17391 - 17396. [Abstract] [Full Text] [PDF]

				C. J. Jorgez, M. Klysik, S. P. Jamin, R. R. Behringer, and M. M. Matzuk Granulosa Cell-Specific Inactivation of Follistatin Causes Female Fertility Defects Mol. Endocrinol., April 1, 2004; 18(4): 953 - 967. [Abstract] [Full Text] [PDF]

				J. P. Hanrahan, S. M. Gregan, P. Mulsant, M. Mullen, G. H. Davis, R. Powell, and S. M. Galloway Mutations in the Genes for Oocyte-Derived Growth Factors GDF9 and BMP15 Are Associated with Both Increased Ovulation Rate and Sterility in Cambridge and Belclare Sheep (Ovis aries) Biol Reprod, April 1, 2004; 70(4): 900 - 909. [Abstract] [Full Text] [PDF]

				S. Mazerbourg, C. Klein, J. Roh, N. Kaivo-Oja, D. G. Mottershead, O. Korchynskyi, O. Ritvos, and A. J. W. Hsueh Growth Differentiation Factor-9 Signaling Is Mediated by the Type I Receptor, Activin Receptor-Like Kinase 5 Mol. Endocrinol., March 1, 2004; 18(3): 653 - 665. [Abstract] [Full Text] [PDF]

				S. Shimasaki, R. K. Moore, F. Otsuka, and G. F. Erickson The Bone Morphogenetic Protein System In Mammalian Reproduction Endocr. Rev., February 1, 2004; 25(1): 72 - 101. [Abstract] [Full Text] [PDF]

				O. M. Onagbesan, V. Bruggeman, P. Van As, K. Tona, J. Williams, and E. Decuypere BMPs and BMPRs in chicken ovary and effects of BMP-4 and -7 on granulosa cell proliferation and progesterone production in vitro Am J Physiol Endocrinol Metab, November 1, 2003; 285(5): E973 - E983. [Abstract] [Full Text] [PDF]

				E. E. Nilsson and M. K. Skinner Bone Morphogenetic Protein-4 Acts as an Ovarian Follicle Survival Factor and Promotes Primordial Follicle Development Biol Reprod, October 1, 2003; 69(4): 1265 - 1272. [Abstract] [Full Text] [PDF]

				D. M. Duffy Growth Differentiation Factor-9 Is Expressed by the Primate Follicle Throughout the Periovulatory Interval Biol Reprod, August 1, 2003; 69(2): 725 - 732. [Abstract] [Full Text] [PDF]

				C. Glister, N. P. Groome, and P. G. Knight Oocyte-Mediated Suppression of Follicle-Stimulating Hormone- and Insulin-Like Growth Factor-Induced Secretion of Steroids and Inhibin-Related Proteins by Bovine Granulosa Cells In Vitro: Possible Role of Transforming Growth Factor {alpha} Biol Reprod, March 1, 2003; 68(3): 758 - 765. [Abstract] [Full Text] [PDF]

				N. Kaivo-Oja, J. Bondestam, M. Kamarainen, J. Koskimies, U. Vitt, M. Cranfield, K. Vuojolainen, J. P. Kallio, V. M. Olkkonen, M. Hayashi, et al. Growth Differentiation Factor-9 Induces Smad2 Activation and Inhibin B Production in Cultured Human Granulosa-Luteal Cells J. Clin. Endocrinol. Metab., February 1, 2003; 88(2): 755 - 762. [Abstract] [Full Text] [PDF]

				W. X. Liao, R. K. Moore, F. Otsuka, and S. Shimasaki Effect of Intracellular Interactions on the Processing and Secretion of Bone Morphogenetic Protein-15 (BMP-15) and Growth and Differentiation Factor-9. IMPLICATION OF THE ABERRANT OVARIAN PHENOTYPE OF BMP-15 MUTANT SHEEP J. Biol. Chem., January 31, 2003; 278(6): 3713 - 3719. [Abstract] [Full Text] [PDF]

				R. K. Moore, F. Otsuka, and S. Shimasaki Molecular Basis of Bone Morphogenetic Protein-15 Signaling in Granulosa Cells J. Biol. Chem., January 3, 2003; 278(1): 304 - 310. [Abstract] [Full Text] [PDF]

				J.-S. Roh, J. Bondestam, S. Mazerbourg, N. Kaivo-Oja, N. Groome, O. Ritvos, and A. J. W. Hsueh Growth Differentiation Factor-9 Stimulates Inhibin Production and Activates Smad2 in Cultured Rat Granulosa Cells Endocrinology, January 1, 2003; 144(1): 172 - 178. [Abstract] [Full Text] [PDF]

				H. Chang, C. W. Brown, and M. M. Matzuk Genetic Analysis of the Mammalian Transforming Growth Factor-{beta} Superfamily Endocr. Rev., December 1, 2002; 23(6): 787 - 823. [Abstract] [Full Text] [PDF]

				J. Huntriss, R. Gosden, M. Hinkins, B. Oliver, D. Miller, A.J. Rutherford, and H.M. Picton Isolation, characterization and expression of the human Factor In the Germline alpha (FIGLA) gene in ovarian follicles and oocytes Mol. Hum. Reprod., December 1, 2002; 8(12): 1087 - 1095. [Abstract] [Full Text] [PDF]

				J. L. Juengel, N. L. Hudson, D. A. Heath, P. Smith, K. L. Reader, S. B. Lawrence, A. R. O'Connell, M. P.E. Laitinen, M. Cranfield, N. P. Groome, et al. Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 Are Essential for Ovarian Follicular Development in Sheep Biol Reprod, December 1, 2002; 67(6): 1777 - 1789. [Abstract] [Full Text] [PDF]

				A. Narula, S. Kilen, E. Ma, J. Kroeger, E. Goldberg, and T. K. Woodruff Smad4 Overexpression Causes Germ Cell Ablation and Leydig Cell Hyperplasia in Transgenic Mice Am. J. Pathol., November 1, 2002; 161(5): 1723 - 1734. [Abstract] [Full Text] [PDF]

				E. E. Nilsson and M. K. Skinner Growth and Differentiation Factor-9 Stimulates Progression of Early Primary but Not Primordial Rat Ovarian Follicle Development Biol Reprod, September 1, 2002; 67(3): 1018 - 1024. [Abstract] [Full Text] [PDF]

				U. A. Vitt, S. Mazerbourg, C. Klein, and A. J.W. Hsueh Bone Morphogenetic Protein Receptor Type II Is a Receptor for Growth Differentiation Factor-9 Biol Reprod, August 1, 2002; 67(2): 473 - 480. [Abstract] [Full Text] [PDF]

				C. P. Leo, S. Y. Hsu, and A. J. W. Hsueh Hormonal Genomics Endocr. Rev., June 1, 2002; 23(3): 369 - 381. [Abstract] [Full Text] [PDF]

				N. Yamamoto, L. K. Christenson, J. M. MCAllister, and J. F. Strauss III Growth Differentiation Factor-9 Inhibits 3'5'-Adenosine Monophosphate-Stimulated Steroidogenesis in Human Granulosa and Theca Cells J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2849 - 2856. [Abstract] [Full Text] [PDF]

				D. Tomic, S.G. Brodie, C. Deng, R.J. Hickey, J.K. Babus, L.H. Malkas, and J.A. Flaws Smad 3 May Regulate Follicular Growth in the Mouse Ovary Biol Reprod, April 1, 2002; 66(4): 917 - 923. [Abstract] [Full Text] [PDF]

				R. Jaatinen, J. Bondestam, T. Raivio, K. Hilden, L. Dunkel, N. Groome, and O. Ritvos Activation of the Bone Morphogenetic Protein Signaling Pathway Induces Inhibin {beta}B-Subunit mRNA and Secreted Inhibin B Levels in Cultured Human Granulosa-Luteal Cells J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1254 - 1261. [Abstract] [Full Text] [PDF]

				F. L. Teixeira Filho, E. C. Baracat, T. H. Lee, C. S. Suh, M. Matsui, R. J. Chang, S. Shimasaki, and G. F. Erickson Aberrant Expression of Growth Differentiation Factor-9 in Oocytes of Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1337 - 1344. [Abstract] [Full Text] [PDF]

				J. G. Hreinsson, J. E. Scott, C. Rasmussen, M. L. Swahn, A. J. W. Hsueh, and O. Hovatta Growth Differentiation Factor-9 Promotes the Growth, Development, and Survival of Human Ovarian Follicles in Organ Culture J. Clin. Endocrinol. Metab., January 1, 2002; 87(1): 316 - 321. [Abstract] [Full Text] [PDF]

				C. Yan, P. Wang, J. DeMayo, F. J. DeMayo, J. A. Elvin, C. Carino, S. V. Prasad, S. S. Skinner, B. S. Dunbar, J. L. Dube, et al. Synergistic Roles of Bone Morphogenetic Protein 15 and Growth Differentiation Factor 9 in Ovarian Function Mol. Endocrinol., June 1, 2001; 15(6): 854 - 866. [Abstract] [Full Text] [PDF]

				T. R. Clarke, Y. Hoshiya, S. E. Yi, X. Liu, K. M. Lyons, and P. K. Donahoe Mullerian Inhibiting Substance Signaling Uses a Bone Morphogenetic Protein (BMP)-Like Pathway Mediated by ALK2 and Induces Smad6 Expression Mol. Endocrinol., June 1, 2001; 15(6): 946 - 959. [Abstract] [Full Text] [PDF]

				T. Wilson, X.-Y. Wu, J. L. Juengel, I. K. Ross, J. M. Lumsden, E. A. Lord, K. G. Dodds, G. A. Walling, J. C. McEwan, A. R. O'Connell, 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, April 1, 2001; 64(4): 1225 - 1235. [Abstract] [Full Text]

				C. Yan and M. M. Matzuk Transgenic Models of Ovarian Failure Reproductive Sciences, January 1, 2001; 8(1_suppl): S30 - S33. [Abstract] [PDF]

				A. R. Zinn The X Chromosome and the Ovary Reproductive Sciences, January 1, 2001; 8(1_suppl): S34 - S36. [Abstract] [PDF]

				K. M. Wasson and A. J. W. Hsueh Ovarian Gene Database Reproductive Sciences, January 1, 2001; 8(1_suppl): S37 - S39. [Abstract] [PDF]

				E. V. Solovyeva, M. Hayashi, K. Margi, C. Barkats, C. Klein, A. Amsterdam, A. J.W. Hsueh, and A. Tsafriri Growth Differentiation Factor-9 Stimulates Rat Theca-Interstitial Cell Androgen Biosynthesis Biol Reprod, October 1, 2000; 63(4): 1214 - 1218. [Abstract] [Full Text]

				C. A. Dooley, G. R. Attia, W. E. Rainey, D. R. Moore, and B. R. Carr Bone Morphogenetic Protein Inhibits Ovarian Androgen Production J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3331 - 3337. [Abstract] [Full Text]

				A. L. Lau, T. R. Kumar, K. Nishimori, J. Bonadio, and M. M. Matzuk Activin beta C and beta E Genes Are Not Essential for Mouse Liver Growth, Differentiation, and Regeneration Mol. Cell. Biol., August 15, 2000; 20(16): 6127 - 6137. [Abstract] [Full Text]

				J. D. Hennebold, M. Tanaka, J. Saito, B. R. Hanson, and E. Y. Adashi Ovary-Selective Genes I: The Generation and Characterization of an Ovary-Selective Complementary Deoxyribonucleic Acid Library Endocrinology, August 1, 2000; 141(8): 2725 - 2734. [Abstract] [Full Text] [PDF]

				K. Oktay, G. Karlikaya, O. Akman, G. K. Ojakian, and M. Oktay Interaction of Extracellular Matrix and Activin-A in the Initiation of Follicle Growth in the Mouse Ovary Biol Reprod, August 1, 2000; 63(2): 457 - 461. [Abstract] [Full Text]

				M. M. Matzuk Editorial: In Search of Binding--Identification of Inhibin Receptors Endocrinology, July 1, 2000; 141(7): 2281 - 2284. [Full Text] [PDF]

				E. A. McGee and A. J. W. Hsueh Initial and Cyclic Recruitment of Ovarian Follicles Endocr. Rev., April 1, 2000; 21(2): 200 - 214. [Abstract] [Full Text]

				U.A. Vitt, M. Hayashi, C. Klein, and A.J.W. Hsueh 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, February 1, 2000; 62(2): 370 - 377. [Abstract] [Full Text]

				S. Soyal, A Amleh, and J Dean FIGalpha, a germ cell-specific transcription factor required for ovarian follicle formation Development, January 11, 2000; 127(21): 4645 - 4654. [Abstract] [PDF]

				A. L. L. Durlinger, P. Kramer, B. Karels, F. H. de Jong, J. Th. J. Uilenbroek, J. A. Grootegoed, and A. P. N. Themmen Control of Primordial Follicle Recruitment by Anti-Mullerian Hormone in the Mouse Ovary Endocrinology, December 1, 1999; 140(12): 5789 - 5796. [Abstract] [Full Text]

				J. Aaltonen, M. P. Laitinen, K. Vuojolainen, R. Jaatinen, N. Horelli-Kuitunen, L. Seppä, H. Louhio, T. Tuuri, J. Sjöberg, R. Bützow, et al. Human Growth Differentiation Factor 9 (GDF-9) and Its Novel Homolog GDF-9B Are Expressed in Oocytes during Early Folliculogenesis J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2744 - 2750. [Abstract] [Full Text]

				S. Shimasaki, R. J. Zachow, D. Li, H. Kim, S.-i. Iemura, N. Ueno, K. Sampath, R. J. Chang, and G. F. Erickson A functional bone morphogenetic protein system in the ovary PNAS, June 22, 1999; 96(13): 7282 - 7287. [Abstract] [Full Text] [PDF]

				J. A. Elvin, C. Yan, P. Wang, K. Nishimori, and M. M. Matzuk Molecular Characterization of the Follicle Defects in the Growth Differentiation Factor 9-Deficient Ovary Mol. Endocrinol., June 1, 1999; 13(6): 1018 - 1034. [Abstract] [Full Text]

				J. A. Elvin, A. T. Clark, P. Wang, N. M. Wolfman, and M. M. Matzuk Paracrine Actions Of Growth Differentiation Factor-9 in the Mammalian Ovary Mol. Endocrinol., June 1, 1999; 13(6): 1035 - 1048. [Abstract] [Full Text]

				F. Otsuka, Z. Yao, T.-h. Lee, S. Yamamoto, G. F. Erickson, and S. Shimasaki Bone Morphogenetic Protein-15. IDENTIFICATION OF TARGET CELLS AND BIOLOGICAL FUNCTIONS J. Biol. Chem., December 8, 2000; 275(50): 39523 - 39528. [Abstract] [Full Text] [PDF]

				F. Otsuka, S. Yamamoto, G. F. Erickson, and S. Shimasaki Bone Morphogenetic Protein-15 Inhibits Follicle-stimulating Hormone (FSH) Action by Suppressing FSH Receptor Expression J. Biol. Chem., March 30, 2001; 276(14): 11387 - 11392. [Abstract] [Full Text] [PDF]

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