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Departments of Pathology (C.Y., M.M.M.), Molecular and Cellular
Biology (P.W., J.D., F.J.D., C.C., S.V.P., S.S.S., B.S.D., M.M.M.), and
Molecular and Human Genetics (J.A.E., M.M.M.) Baylor College of
Medicine Houston, Texas, 77030
Department of Tissue
Growth and Repair (J.L.D., A.J.C.) Genetics Institute,
Inc. Cambridge, Massachusetts 02140
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONRESULTSDISCUSSIONMATERIALS AND METHODSREFERENCES |
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONRESULTSDISCUSSIONMATERIALS AND METHODSREFERENCES |
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knockout mice (4)], formation of secondary follicles [e.g.
Gdf9 knockout mice (5)], formation of antral follicles
[e.g. FSHß knockout mice (6)], ovulation
[e.g. cyclooxygenase 2 (7) and progesterone receptor
knockout mice (8)], or postovulation [e.g. Mater knockout
mice (9)]. Whereas mutations in oocyte-expressed genes
(e.g. Fig, kit receptor, and Mater) result in intrinsic
defects in the oocyte or early embryo (4, 9, 10), growth
differentiation factor 9 (GDF-9) is the only known oocyte-secreted
growth factor that is required for somatic cell function in mice
in vivo. Using Gdf9 knockout mice, we have shown
that GDF-9 is directly required for granulosa cell growth and
differentiation and indirectly for oocyte meiotic competence and
formation of a theca (5, 11, 12). Gdf9 mRNA and GDF-9 protein are not only expressed at the primary follicle stage but are also present in oocytes through ovulation (13, 14, 15). Since mice lacking GDF-9 have a block at the primary follicle stage, fail to form a theca, and eventually demonstrate defects in meiotic competence, it was unclear from these knockout studies whether GDF-9 also plays a role at later stages of folliculogenesis. It was therefore important to determine the function of GDF-9 in the periovulatory period since oocyte-secreted growth factors had been identified to play key regulatory functions in this period. Using recombinant mouse GDF-9, we demonstrated that GDF-9 can regulate a diverse number of genes and processes in the periovulatory stage, including cumulus expansion, induction of hyaluronan synthase 2, cyclooxygenase 2, and the EP2 PGE2 receptor, and inhibition of LH receptor and urokinase plasminogen activator (13, 15, 16). In addition, recombinant rat GDF-9 stimulates rat preantral follicle growth and also stimulates basal estradiol production in granulosa cells (17, 18). Thus, GDF-9 functions as a multipurpose oocyte-secreted growth factor during the early stages of folliculogenesis and in the periovulatory period.
Using a homology-based cloning strategy, we fortuitously cloned GDF-9 homologs from the mouse and human that we termed bone morphogenetic protein 15 (BMP-15) (19) [also called growth differentiation factor 9B (20)]. In addition to the 52% identity with GDF-9, BMP-15 had several interesting features. First, Bmp15 mRNA was exclusively expressed in oocytes in an identical pattern as Gdf9 (15, 19). Second, mouse Bmp15 and human BMP15 map to syntenic positions on the X chromosome. Third, similar to GDF-9, BMP-15 protein lacks the mature peptide cysteine that normally forms an intermolecular disulfide bond in the other TGFß superfamily members. These findings suggest that BMP-15 and GDF-9 may directly interact (i.e. form heterodimers) or functionally interact (i.e. play redundant or antagonistic roles). Recent evidence from studies in sheep suggests interacting roles of these proteins in the ovary. The BMP15 gene was cloned in sheep and shown to be mutated in Inverdale and Hanna sheep carrying the fecundity X (FecXI and FecXH) mutations (21). Both strains have mutations in the mature peptide sequence. Sheep heterozygous for these BMP15 mutations show an increased ovulation frequency resulting in more twins and triplets. Surprisingly, sheep homozygous for these mutations are infertile and have a block in folliculogenesis that phenocopies the mouse Gdf9 knockout ovarian phenotype. Thus, BMP-15 appears to be the second known oocyte-secreted growth factor that is critical for ovarian function.
In this report, we used the previously isolated mouse Bmp15 gene sequences (19) to create male and female mice with a null mutation in the X-linked Bmp15 gene. These Bmp15 null female mice are viable but display reproductive defects. In addition, we have intercrossed these Bmp15 null mice with mice carrying a mutation in the autosomal Gdf9 gene to uncover genetic interactions. These knockout mouse models have helped us define the important roles of BMP-15 and GDF-9 in oocyte-somatic cell interactions during folliculogenesis and in the periovulatory period.
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RESULTS |
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TOPABSTRACTINTRODUCTIONRESULTSDISCUSSIONMATERIALS AND METHODSREFERENCES |
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). Recombination of this targeting
vector and the endogenous Bmp15 locus was anticipated to
yield a null allele because no mature (active) BMP-15 could be
synthesized if the gene sequences encoding it were deleted. A similar
strategy had been employed to generate a null allele in the
Gdf9 locus (5).
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, top). Using Southern blot analysis of DNA, a
Bmp15 exon 2 probe demonstrated a lack of a hybridizable
signal in the DNA derived from XBmp15tm1Y
and
XBmp15tm1XBmp15tm1
mice but not XBmp15tm1X or XY mice (Fig. 1B, bottom). This confirmed that the
Bmp15tm1Zuk allele is a null allele.
Fertility Analysis of Bmp15 Mutant Mice
Chimeric males, null males, heterozygous females, and null females
were all viable and failed to demonstrate any gross developmental
defects. In addition, male chimeric and Bmp15 null males
were fertile, and Bmp15 null males had normal testis size
[87.58 ± 2.42 ng/testis (n = 18)] compared with wild-type
controls [87.27 ± 2.53 ng/testis (n = 11)]. The viability
of Bmp15 mutant mice and the fertility of the chimeric and
null males are consistent with the limited adult ovary-specific
expression of Bmp15 mRNA (19).
To determine whether Bmp15 plays a key ovarian function in
females, heterozygous and homozygous mutant females were mated to
males. In contrast to GDF-9, which is absolutely required for fertility
in females, Bmp15 homozygous mutants (C57/129 hybrid
background) were subfertile when bred over a 1-yr period (Table 1). When the Bmp15 mutation
was maintained on a 129SvEv inbred background strain (in which females
are normally less fertile), the Bmp15 homozygous null
females displayed a consistent (although more severe) subfertility
compared with the Bmp15 heterozygotes (Table 1). Both the
number of pups per litter and the number of litters per month were
reduced for the Bmp15-/- females
from either hybrid or inbred genetic backgrounds. Thus, BMP-15 plays an
important role in female reproduction in mice but is not as essential
as GDF-9 or its sheep ortholog.
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). These
findings would be consistent with the ability of
Bmp15-/- mice to become pregnant.
However, occasional Bmp15-/- ovaries
at different ages demonstrated very few follicles and had an increased
number of zona pellucida (ZP) remnants (data not shown; see below).
Single rare Bmp15-/- and
Bmp15+/- mice had unilateral or
bilateral cysts at 1 yr of age. These findings have never been seen in
wild-type mice in our laboratory.
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), Bmp15-/- ovaries
occasionally had denuded oocytes that were larger than normal and had
few cumulus cells surrounding the oocytes (Fig. 2F). These findings
suggested that follicular recruitment and the number of preovulatory
follicles were likely normal in the
Bmp15-/- mice but that a percentage
of the oocytes were trapped within follicles and were not released. A
similar phenotype is also seen for the EP2 PGE2
receptor knockout mice (22) whereas an absolute failure to ovulate is
seen with cyclooxygenase 2 and progesterone receptor knockout mice (7, 8). In addition to these ovulation defects,
Bmp15-/- mice also demonstrated a
reduction of oocytes that could develop to embryos although
Bmp15+/- oocytes also appeared to
have some reduction compared with wild-type mice (Table 2; see below).
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). In contrast, Bmp15
mRNA levels were higher in the Gdf9-/- ovary
samples compared with control ovaries (Fig. 3). This relative increase
in Bmp15 mRNA was due to a dramatic increase in oocytes/unit
volume in the Gdf9-/- ovaries (5).
We have confirmed this by showing that four other oocyte-specific genes
also show a relative increase in mRNA levels in the
Gdf9-/- ovaries compared with
wild-type ovaries (C. Yang, P. Wang, and M. M. Matzuk, unpublished
data). Thus, the abnormalities in the Gdf9 knockout ovaries
are not due to transcriptional inactivation of the Bmp15
gene nor is there a compensatory increase of Gdf9 mRNA in
the Bmp15 knockout ovaries.
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). In contrast, the
Bmp15-/-Gdf9+/-
females on a C57/129 background that gave birth produced even fewer
pups per litter (3.67 ± 0.22) compared with the
Bmp15-/- females (4.93 ±
0.25). Furthermore, the number of litters per month was further reduced
to approximately half of the controls, and four females were completely
infertile. We also saw an increased incidence of death in these
breeding
Bmp15-/-Gdf9+/-
females (4 of 21 breeding females) but not in
Bmp15-/-Gdf9+/-
females that were caged without males; we attribute these deaths
to a failure to deliver singlets and subsequent intrauterine infection.
Recent breeding of 129 inbred
Bmp15-/-Gdf9+/-
females over a 6-month period failed to produce any offspring in
contrast to the breeding of 129 inbred
Bmp15+/-Gdf9+/- females
over a 4- to 6-month period, which yielded 64 litters (0.73
litters/month) with an average litter size of 4.39 (Table 1). These
findings for the 129 inbred
Bmp15-/-Gdf9+/-
females are even more dramatic than the
Bmp15-/-Gdf9+/-
hybrid strain data and 129 inbred
Bmp15-/- female mice that breed
poorly. Thus, by reducing the dosage of these two related
oocyte-expressed proteins, we have uncovered important genetic
interactions.
To further understand the subfertility defects of the
Bmp15-/-Gdf9+/-
females, we analyzed the ovaries histologically. Similar to the
Bmp15-/- ovaries, normal
folliculogenesis and corpora lutea could be observed in a minority of
Bmp15-/-Gdf9+/-
ovaries up through 1 yr (Fig. 4, A and
F). However, abnormalities were observed in five of nine ovaries from
6- to 7-month-old mice, three of five 9-month-old mice, and 12 of
fourteen 11- to 12-month-old mice. These abnormalities included
decreased numbers of late-stage follicles, increased oocyte loss, and
increased ZP remnants, accumulation of periodic acid Schiff
(PAS)-positive material in the interstitium, follicles with multiple
oocytes, and absence of corpora lutea (Fig. 4, B and C). This
progressed to the point where there were very few oocytes and follicles
in some ovaries by 1 yr of age (Fig. 4G). Thus, these findings suggest
that BMP-15 and GDF-9 play synergistic roles in oocyte survival and
folliculogenesis.
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and 7 were analyzed using antibodies specific for ZP protein 1
(ZP1), 2 (ZP2), or 3 (ZP3) or a nonspecific antibody. Antibodies to
ZP1, ZP2, or ZP3 stained the ZP around intact oocytes and also detected
the prominent remnants centrally (Fig. 5, A–C), confirming that these are remnants of ZP after the oocyte had
disappeared. The nonspecific antibody failed to detect any signal in
the ovaries (Fig. 5D) confirming the specificity of the anti- ZP
antibodies. These ZP remnants appear to be quite stable after oocyte
loss (see below).
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, D and E). To quantitatively study these findings, we
analyzed multiple adjacent sections (8–10 sections per pair of
ovaries) of 129SvEv inbred ovaries from
Bmp15-/-Gdf9+/-
vs.
Bmp15+/-Gdf9+/-
mice (littermate controls). Whereas only two of eight
Bmp15+/-Gdf9+/-
mice contained follicles with multiple oocytes (two follicles total),
four of eight
Bmp15-/-Gdf9+/-
mice contained multiple oocytes (eight follicles total). Interestingly,
two
Bmp15-/-Gdf9+/-
mice and one
Bmp15+/-Gdf9+/-
mouse had follicles with three oocytes in the follicle (Fig. 4E). These
findings are rare for wild-type inbred 129SvEv mice. Thus, the dosage
of these ligands appears to somehow alter the development of the
granulosa cell layers around individual oocytes, allowing the formation
of these double and triple oocyte follicles.
Since folliculogenesis was relatively normal in the
Bmp15-/-Gdf9+/-
ovaries at early time points, we analyzed the ability of the
Bmp15-/-Gdf9+/-
oocytes to be pharmacologically released and fertilized in
vivo. Whereas the
Bmp15-/-Gdf9+/-
mice had high numbers of oocytes released (Table 2), only 13.8% of
these oocytes developed to embryos. Analysis of eggs from
Bmp15-/-Gdf9+/-
females that were subjected to PMSG/hCG treatment but were not mated
with males revealed the likely cause of the
Bmp15-/-Gdf9+/-
defects. Normally, cumulus cell-egg complexes from wild-type and
Gdf9+/- mice demonstrate a resilient
adhesion of cumulus cells and eggs upon removal of the complexes from
the oviduct (Fig. 6A). In contrast,
cumulus cells fail to adhere to eggs isolated from the oviducts of
Bmp15-/-Gdf9+/-
mutant mice (Fig. 6B). A similar finding was also seen for many of the
cumulus cell-egg complexes isolated from
Bmp15-/- mice. Furthermore,
treatment of immature
Bmp15-/-Gdf9+/-
mice with PMSG for 48 h and subsequent analysis of their ovaries
8 h after hCG injection revealed the presence of some follicles in
which cumulus expansion had not occurred or examples of large denuded
oocytes (oocytes that were completely lacking cumulus cells) (Fig. 4I).
This finding was in contrast to
Gdf9+/- mice (Fig. 4H). Analysis of
individual sections of ovaries from wild-type or
Gdf9+/- ovaries revealed 25
preovulatory follicles in which cumulus expansion appeared normal and
29 oocytes of antral follicles that were appropriate in size (11).
However, analysis of Bmp15-/- or
Bmp15-/-Gdf9+/-
ovaries revealed 11 of 19 antral follicles where absence of cumulus
expansion had occurred or where oocytes were larger than normal in
size. In addition to these findings, there was one case in which the
cumulus granulosa cells were seen invading the ZP. These findings were
not unique to pharmacologically treated mice but were also observed in
seven of ten 11- to 12-month-old
Bmp15-/-Gdf9+/-
mice in which denuded oocytes in antral follicles (total of seven
oocytes with cumulus cell defect) and oocytes trapped in corpora lutea
(total of eight trapped oocytes) were observed. Six of six
Bmp15+/- mice of the same age failed
to demonstrate these defects. We believe that these findings are part
of the variation in the cumulus cell adhesion/oocyte-cumulus cell
interaction phenotype. Thus, these studies demonstrate that BMP-15 and
GDF-9 play functionally redundant roles in cumulus expansion and
maintenance of a cohesive interaction between cumulus cells and oocytes
or eggs that influences subsequent fertility.
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). Furthermore, similar to
Gdf9-/- mice, unilateral and
bilateral cysts were grossly (Fig. 7A) and microscopically (Fig. 7E)
present. Only one cyst per ovary was present in these double mutant
mice as in the Gdf9-/- mice.
At later time points, there were a number of unique abnormalities found
in the
Bmp15-/-Gdf9-/-
ovaries. These abnormalities included increased loss of oocytes,
increased ZP remnants, complete absence of oocytes, and proliferation
of cells in the interstitium (sometimes PAS-positive) (Fig. 7, C–F),
and a rare mouse that displayed a transformation of the granulosa cells
into Sertoli-like cells (Fig. 7, G and H) similar to mice lacking
inhibin (23) or estrogen receptors and ß (24). Interestingly,
accumulation of ZP remnants are seen after loss of oocytes in the
Gdf9-/- ovaries (5) but are not seen
after loss of oocytes in animal models that have blocks at later stages
such as FSHß, cyclooxygenase 2, or progesterone receptor knockouts
(6, 7, 8). It is not clear whether there are altered proteolytic
processing defects in the ovaries of mice that have blocks at the
primary follicle stage vs. blocks at later stages. Thus,
unopposed BMP-15 is not the cause of the Gdf9 knockout
phenotype but BMP-15 appears to play some additional roles along with
GDF-9 in oocyte survival. |
DISCUSSION |
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TOPABSTRACTINTRODUCTIONRESULTSDISCUSSIONMATERIALS AND METHODSREFERENCES |
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Gdf9-/- and
Bmp15-/-Gdf9-/-
mice develop unilateral and bilateral cysts with high frequency (Ref. 5
and the current study). These cysts can become very large (Fig. 7), and
analysis of the cystic ovaries of these mice or after regression of the
cysts demonstrates a dramatic reduction in the number of oocytes
(i.e. the cysts lead to decreased oocyte survival). We
believe that these findings in our knockout mice have important
implications in humans. Polycystic ovarian syndrome (PCOS) is a major
cause of reduced fertility in women, and our findings suggest that the
presence of cysts in the ovaries of these women could likewise lead to
increased oocyte loss through direct structural destruction or via
indirect growth factor/hormonal effects.
Unlike Bmp15+/- mice, BMP15 heterozygous mutant sheep demonstrate increased fertility (i.e., increased twins and triplets), suggesting that the BMP-15 propeptide sequences (present as the sheep mutations are in the mature peptide encoding region) are acting in a dominant negative fashion. This BMP-15 propeptide may be somehow interfering with GDF-9 homodimer, BMP-15 homodimer, and/or GDF-9/BMP-15 heterodimer formation. For example, the BMP-15 propeptide may preferentially bind to a wild-type GDF-9 propeptide monomer to cause decreased BMP-15/GDF-9 heterodimers and shift the equilibrium toward increased BMP-15 homodimers.
Interestingly, sheep homozygous for null mutations in the
BMP15 gene do not phenocopy Bmp15 knockout mice
but instead resemble Gdf9-/- mice
(i.e. homozygotes are infertile due to a block at the
primary follicle stage). How might one explain these findings? Based on
the available animal models and in vitro studies, two
different models could be evoked to explain the functions of GDF-9 and
BMP-15 in sheep vs. mice (Fig. 8). In model A (the mouse model), GDF-9
homodimers would be the most bioactive and play the major function.
This model is based on our findings from
Gdf9-/- mice (5, 11, 12), which
display an early block in folliculogenesis, and also on the present
study on the Bmp15-/- mice (which
have a defect in late folliculogenesis and ovulation). Furthermore,
mouse GDF-9 homodimers, but not mouse BMP-15 homodimers, are active in
our mouse in vitro bioassays (13, 16). A similar situation
has been shown recently by our group in the case of the activin ßA
and ßB monomers (26); using a gene "knockin" strategy, we
demonstrated that activin ßB (which shows 63% amino acid identity in
the mature peptide sequence) can replace activin ßA for some, but not
all, functions, demonstrating that ßB is less bioactive than ßA.
However, in model B (the sheep model), BMP-15 homodimers would be
postulated to be the most bioactive compared with either GDF-9
homodimers or BMP-15/GDF-9 heterodimers. This model would explain how
the sheep BMP15 homozygous mutant phenotype mimics the
Gdf9-/- mouse ovarian phenotype.
Interestingly, mouse and sheep GDF-9 proteins are highly conserved
whereas mouse and sheep BMP-15 proteins have diverged greatly (78%
amino acid identity). Thus, it is possible that this protein divergence
has altered the biopotency of these proteins, allowing BMP15 to become
the more essential protein in sheep. Although these models assume
signaling of the ligands through the same receptor, we cannot rule out
evolutionary divergence of a common GDF-9 or BMP-15 receptor (or
multiple receptors) to permit higher affinity interaction of the sheep
receptor with BMP-15 homodimers to explain the in vivo
findings. However, recent studies demonstrate that recombinant human
BMP-15 stimulates in vitro rat granulosa cell proliferation
and decreases FSH-induced progesterone production (27). This finding
suggests that the BMP-15 receptors are conserved between species.
Future structure-function and receptor binding studies should help us
clarify the active forms of these ligands in the different mammalian
species and determine whether BMP-15, GDF-9, or both are essential for
human fertility.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONRESULTSDISCUSSIONMATERIALS AND METHODSREFERENCES |
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)]. Linearized vector was electroporated into the
hprt-negative AB2.1 ES cell line, cell clones were selected in HAT
(hypoxanthine, aminopterine, and thymidine) and FIAU [1-(2'-
deoxy-2'fluoro-ß-D-arabinofuranosyl)-5-iodouracil],
and DNA from the clones analyzed by Southern blot and targeted ES cell
clones were expanded and injected into blastocysts as described
previously (23, 28, 29). Fourteen percent of the ES cell clones were
targeted at the Bmp15 locus (data not shown), and two of
these ES cell clones (Bmp15-79-D7 and
Bmp15-79-F7), which were injected into blastocysts, produced
male chimeras that successfully transmitted the mutant
Bmp15tm1Zuk allele to F1 female
offspring. F1 and F2 female heterozygotes and
F2 null male offspring were intercrossed to
produce Bmp15 null homozygotes. Chimeras were either bred to
C57BL6/J females to produce 129SvEv/C57BL6/J hybrid mice or to 129SvEv
females to produce 129SvEv inbred mice. Southern blot analysis was used
for genotype analysis of all Bmp15 mutant offspring as shown
(Fig. 1B) and all Gdf9 mutant offspring as described
(5).
Breeding Experiments
Bmp15 heterozygous and homozygous mutant females from
both hybrid (129SvEv/C57BL6J) and inbred (129SvEv) genetic backgrounds
were bred to males of the same genetic backgrounds at 6 weeks of age
and breeding was continued for up to 1 yr. To generate the
Bmp15/Gdf9 double mutant mice, mice carrying the
Gdf9tm1Zuk mutation (5) on either
hybrid or 129SvEv inbred genetic backgrounds were bred to
Bmp15 mutant mice of similar genetic backgrounds. Breeding
of the double mutants was also initiated at 6 weeks of age.
Immunohistological Analysis
Immunohistological analysis was carried out using
epitope-selected antibodies purified from antisera of rabbits immunized
with porcine ZP proteins as previously described (30, 31). To select
ZP1-, 2-, and 3-specific antibodies that would recognize mouse ZP
proteins, we used an epitope selection method to enhance for
cross-species ZP epitopes. Antibodies recognizing all three porcine ZP
proteins were epitope selected using human ZP proteins made from cDNAs
expressed using the baculovirus expression system (32, 33). Briefly,
antibodies were incubated with each of the three human ZP proteins that
had been isolated from SF9 insect cell lines. The individual proteins
were transferred to polyvinylidenefluoride (PVDF) membrane and
incubated with antiserum. Nonspecific antibodies were washed from the
membrane and ZP-specific antibodies were eluted with 200 mM
glycine buffer, pH 2.7, which was neutralized to pH 7. Antibody
specificity to each of the ZP proteins was demonstrated by SDS-PAGE and
immunoblot analysis as previously described (32, 34, 35).
Other Methods
RNA isolation, Northern blot analysis, histological analysis,
pharmacological superovulation, and statistical methods were performed
as described previously (5, 6, 12, 13, 19) and have been described
briefly in the body of the text or the figure legends.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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These studies were supported in part by the NIH Specialized Cooperative Centers Program in Reproduction Research (Grant HD-07495) and NIH Grant HD-33438 (to M.M.M.).
Received for publication January 5, 2001. Revision received February 23, 2001. Accepted for publication March 16, 2001.
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TOPABSTRACTINTRODUCTIONRESULTSDISCUSSIONMATERIALS AND METHODSREFERENCES |
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J. Tejomurtula, K.-B. Lee, S. K. Tripurani, G. W. Smith, and J. Yao Role of Importin Alpha8, a New Member of the Importin Alpha Family of Nuclear Transport Proteins, in Early Embryonic Development in Cattle Biol Reprod, August 1, 2009; 81(2): 333 - 342. [Abstract] [Full Text] [PDF]
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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]
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J. L Juengel, N. L Hudson, M. Berg, K. Hamel, P. Smith, S. B Lawrence, L. Whiting, and K. P McNatty Effects of active immunization against growth differentiation factor 9 and/or bone morphogenetic protein 15 on ovarian function in cattle Reproduction, July 1, 2009; 138(1): 107 - 114. [Abstract] [Full Text] [PDF]
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C. R. Nicholas, S. L. Chavez, V. L. Baker, and R. A. Reijo Pera Instructing an Embryonic Stem Cell-Derived Oocyte Fate: Lessons from Endogenous Oogenesis Endocr. Rev., May 1, 2009; 30(3): 264 - 283. [Abstract] [Full Text] [PDF]
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P. K. Nicholls, C. A. Harrison, R. B. Gilchrist, P. G. Farnworth, and P. G. Stanton Growth Differentiation Factor 9 Is a Germ Cell Regulator of Sertoli Cell Function Endocrinology, May 1, 2009; 150(5): 2481 - 2490. [Abstract] [Full Text] [PDF]
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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]
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E. A McLaughlin and S. C McIver Awakening the oocyte: controlling primordial follicle development Reproduction, January 1, 2009; 137(1): 1 - 11. [Abstract] [Full Text] [PDF]
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 Q. Li, S. A. Pangas, C. J. Jorgez, J. M. Graff, M. Weinstein, and M. M. Matzuk Redundant Roles of SMAD2 and SMAD3 in Ovarian Granulosa Cells In Vivo Mol. Cell. Biol., December 1, 2008; 28(23): 7001 - 7011. [Abstract] [Full Text] [PDF]
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Q. Li, L. J. McKenzie, and M. M. Matzuk Revisiting oocyte-somatic cell interactions: in search of novel intrafollicular predictors and regulators of oocyte developmental competence Mol. Hum. Reprod., December 1, 2008; 14(12): 673 - 678. [Abstract] [Full Text] [PDF]
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Q.-Y. Sun, K. Liu, and K. Kikuchi Oocyte-Specific Knockout: A Novel In Vivo Approach for Studying Gene Functions During Folliculogenesis, Oocyte Maturation, Fertilization, and Embryogenesis Biol Reprod, December 1, 2008; 79(6): 1014 - 1020. [Abstract] [Full Text] [PDF]
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C. J. McIntosh, S. Lun, S. Lawrence, A. H. Western, K. P. McNatty, and J. L. Juengel The Proregion of Mouse BMP15 Regulates the Cooperative Interactions of BMP15 and GDF9 Biol Reprod, November 1, 2008; 79(5): 889 - 896. [Abstract] [Full Text] [PDF]
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Z. Z. Zhao, J. N. Painter, J. S. Palmer, P. M. Webb, N. K. Hayward, D. C. Whiteman, D. I. Boomsma, N. G. Martin, D. L. Duffy, and G. W. Montgomery Variation in bone morphogenetic protein 15 is not associated with spontaneous human dizygotic twinning Hum. Reprod., October 1, 2008; 23(10): 2372 - 2379. [Abstract] [Full Text] [PDF]
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 Y. Obata, M. Villemure, T. Kono, and T. Taketo Transmission of Y chromosomes from XY female mice was made possible by the replacement of cytoplasm during oocyte maturation PNAS, September 16, 2008; 105(37): 13918 - 13923. [Abstract] [Full Text] [PDF]
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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]
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 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]
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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]
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M. Vallee, K. Aiba, Y. Piao, M.-F. Palin, M. S H Ko, and M.-A. Sirard Comparative analysis of oocyte transcript profiles reveals a high degree of conservation among species Reproduction, April 1, 2008; 135(4): 439 - 448. [Abstract] [Full Text] [PDF]
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 R. B. Gilchrist, M. Lane, and J. G. Thompson Oocyte-secreted factors: regulators of cumulus cell function and oocyte quality Hum. Reprod. Update, March 1, 2008; 14(2): 159 - 177. [Abstract] [Full Text] [PDF]
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C. X. Yeo, R. B. Gilchrist, J. G. Thompson, and M. Lane Exogenous growth differentiation factor 9 in oocyte maturation media enhances subsequent embryo development and fetal viability in mice Hum. Reprod., January 1, 2008; 23(1): 67 - 73. [Abstract] [Full Text] [PDF]
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 Y.-Q. Su, K. Sugiura, K. Wigglesworth, M. J. O'Brien, J. P. Affourtit, S. A. Pangas, M. M. Matzuk, and J. J. Eppig Oocyte regulation of metabolic cooperativity between mouse cumulus cells and oocytes: BMP15 and GDF9 control cholesterol biosynthesis in cumulus cells Development, January 1, 2008; 135(1): 111 - 121. [Abstract] [Full Text] [PDF]
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J. L. Kipp, S. M. Kilen, T. K. Woodruff, and K. E. Mayo Activin Regulates Estrogen Receptor Gene Expression in the Mouse Ovary J. Biol. Chem., December 14, 2007; 282(50): 36755 - 36765. [Abstract] [Full Text] [PDF]
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 R. A. Veitia Exploring the Molecular Etiology of Dominant-Negative Mutations PLANT CELL, December 1, 2007; 19(12): 3843 - 3851. [Full Text] [PDF]
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A. Bettegowda, J. Yao, A. Sen, Q. Li, K.-B. Lee, Y. Kobayashi, O. V. Patel, P. M. Coussens, J. J. Ireland, and G. W. Smith JY-1, an oocyte-specific gene, regulates granulosa cell function and early embryonic development in cattle PNAS, November 6, 2007; 104(45): 17602 - 17607. [Abstract] [Full Text] [PDF]
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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]
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 S. A. Pangas, C. J. Jorgez, M. Tran, J. Agno, X. Li, C. W. Brown, T. R. Kumar, and M. M. Matzuk Intraovarian Activins Are Required for Female Fertility Mol. Endocrinol., October 1, 2007; 21(10): 2458 - 2471. [Abstract] [Full Text] [PDF]
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K. Mayo, L. Jameson, and T. K. Woodruff Eggs in the Nest Endocrinology, August 1, 2007; 148(8): 3577 - 3579. [Full Text] [PDF]
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Y. Chen, W. N. Jefferson, R. R. Newbold, E. Padilla-Banks, and M. E. Pepling Estradiol, Progesterone, and Genistein Inhibit Oocyte Nest Breakdown and Primordial Follicle Assembly in the Neonatal Mouse Ovary in Vitro and in Vivo Endocrinology, August 1, 2007; 148(8): 3580 - 3590. [Abstract] [Full Text] [PDF]
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K. Sugiura, Y.-Q. Su, F. J. Diaz, S. A. Pangas, S. Sharma, K. Wigglesworth, M. J. O'Brien, M. M. Matzuk, S. Shimasaki, and J. J. Eppig Oocyte-derived BMP15 and FGFs cooperate to promote glycolysis in cumulus cells Development, July 15, 2007; 134(14): 2593 - 2603. [Abstract] [Full Text] [PDF]
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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]
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G. B John, L. J Shirley, T. D Gallardo, and D. H Castrillon Specificity of the requirement for Foxo3 in primordial follicle activation Reproduction, May 1, 2007; 133(5): 855 - 863. [Abstract] [Full Text] [PDF]
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D. L. Russell and R. L. Robker Molecular mechanisms of ovulation: co-ordination through the cumulus complex Hum. Reprod. Update, May 1, 2007; 13(3): 289 - 312. [Abstract] [Full Text] [PDF]
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 F. J. Diaz, K. Wigglesworth, and J. J. Eppig Oocytes determine cumulus cell lineage in mouse ovarian follicles J. Cell Sci., April 15, 2007; 120(8): 1330 - 1340. [Abstract] [Full Text] [PDF]
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M. Hsieh, D. Lee, S. Panigone, K. Horner, R. Chen, A. Theologis, D. C. Lee, D. W. Threadgill, and M. Conti Luteinizing Hormone-Dependent Activation of the Epidermal Growth Factor Network Is Essential for Ovulation Mol. Cell. Biol., March 1, 2007; 27(5): 1914 - 1924. [Abstract] [Full Text] [PDF]
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L. Liu, S. Rajareddy, P. Reddy, C. Du, K. Jagarlamudi, Y. Shen, D. Gunnarsson, G. Selstam, K. Boman, and K. Liu Infertility caused by retardation of follicular development in mice with oocyte-specific expression of Foxo3a Development, January 1, 2007; 134(1): 199 - 209. [Abstract] [Full Text] [PDF]
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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]
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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]
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K.R. Barnett, C. Schilling, C.R. Greenfeld, D. Tomic, and J.A. Flaws Ovarian follicle development and transgenic mouse models Hum. Reprod. Update, September 1, 2006; 12(5): 537 - 555. [Abstract] [Full Text] [PDF]
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I.B. Carlsson, J.E. Scott, J.A. Visser, O. Ritvos, A.P.N. Themmen, and O. Hovatta Anti-Mullerian hormone inhibits initiation of growth of human primordial ovarian follicles in vitro Hum. Reprod., September 1, 2006; 21(9): 2223 - 2227. [Abstract] [Full Text] [PDF]
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P. G Knight and C. Glister TGF-{beta} superfamily members and ovarian follicle development. Reproduction, August 1, 2006; 132(2): 191 - 206. [Abstract] [Full Text] [PDF]
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R. L Jones, C. Stoikos, J. K Findlay, and L. A Salamonsen TGF-{beta} superfamily expression and actions in the endometrium and placenta. Reproduction, August 1, 2006; 132(2): 217 - 232. [Abstract] [Full Text] [PDF]
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O. Yoshino, H. E. McMahon, S. Sharma, and S. Shimasaki A unique preovulatory expression pattern plays a key role in the physiological functions of BMP-15 in the mouse PNAS, July 11, 2006; 103(28): 10678 - 10683. [Abstract] [Full Text] [PDF]
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S. Mazerbourg and A. J.W. Hsueh Genomic analyses facilitate identification of receptors and signalling pathways for growth differentiation factor 9 and related orphan bone morphogenetic protein/growth differentiation factor ligands Hum. Reprod. Update, July 1, 2006; 12(4): 373 - 383. [Abstract] [Full Text] [PDF]
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S. Assou, T. Anahory, V. Pantesco, T. Le Carrour, F. Pellestor, B. Klein, L. Reyftmann, H. Dechaud, J. De Vos, and S. Hamamah The human cumulus-oocyte complex gene-expression profile Hum. Reprod., July 1, 2006; 21(7): 1705 - 1719. [Abstract] [Full Text] [PDF]
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S. A. Pangas, X. Li, E. J. Robertson, and M. M. Matzuk Premature Luteinization and Cumulus Cell Defects in Ovarian-Specific Smad4 Knockout Mice Mol. Endocrinol., June 1, 2006; 20(6): 1406 - 1422. [Abstract] [Full Text] [PDF]
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 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]
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 L. C. Layman BMP15--The First True Ovarian Determinant Gene on the X-Chromosome? J. Clin. Endocrinol. Metab., May 1, 2006; 91(5): 1673 - 1676. [Full Text] [PDF]
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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]
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J. L Juengel, K. L Reader, A. H Bibby, S. Lun, I. Ross, L. J Haydon, and K. P McNatty The role of bone morphogenetic proteins 2, 4, 6 and 7 during ovarian follicular development in sheep: contrast to rat. Reproduction, March 1, 2006; 131(3): 501 - 513. [Abstract] [Full Text] [PDF]
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A. Roy and M. M Matzuk Deconstructing mammalian reproduction: using knockouts to define fertility pathways Reproduction, February 1, 2006; 131(2): 207 - 219. [Abstract] [Full Text] [PDF]
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H. Shiina, T. Matsumoto, T. Sato, K. Igarashi, J. Miyamoto, S. Takemasa, M. Sakari, I. Takada, T. Nakamura, D. Metzger, et al. From the Cover: Premature ovarian failure in androgen receptor-deficient mice PNAS, January 3, 2006; 103(1): 224 - 229. [Abstract] [Full Text] [PDF]
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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]
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W. Jefferson, R. Newbold, E. Padilla-Banks, and M. Pepling Neonatal Genistein Treatment Alters Ovarian Differentiation in the Mouse: Inhibition of Oocyte Nest Breakdown and Increased Oocyte Survival Biol Reprod, January 1, 2006; 74(1): 161 - 168. [Abstract] [Full Text] [PDF]
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S. Mazerbourg, K. Sangkuhl, C.-W. Luo, S. Sudo, C. Klein, and A. J. W. Hsueh Identification of Receptors and Signaling Pathways for Orphan Bone Morphogenetic Protein/Growth Differentiation Factor Ligands Based on Genomic Analyses J. Biol. Chem., September 16, 2005; 280(37): 32122 - 32132. [Abstract] [Full Text] [PDF]
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J. M. A. Tullet, V. Pocock, J. H. Steel, R. White, S. Milligan, and M. G. Parker Multiple Signaling Defects in the Absence of RIP140 Impair Both Cumulus Expansion and Follicle Rupture Endocrinology, September 1, 2005; 146(9): 4127 - 4137. [Abstract] [Full Text] [PDF]
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 M-O Faure, L Nicol, S Fabre, J Fontaine, N Mohoric, A McNeilly, and C Taragnat BMP-4 inhibits follicle-stimulating hormone secretion in ewe pituitary J. Endocrinol., July 1, 2005; 186(1): 109 - 121. [Abstract] [Full Text] [PDF]
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W. Yan, L. Ma, P. Stein, S. A. Pangas, K. H. Burns, Y. Bai, R. M. Schultz, and M. M. Matzuk Mice Deficient in Oocyte-Specific Oligoadenylate Synthetase-Like Protein OAS1D Display Reduced Fertility Mol. Cell. Biol., June 1, 2005; 25(11): 4615 - 4624. [Abstract] [Full Text] [PDF]
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R. A. Dragovic, L. J. Ritter, S. J. Schulz, F. Amato, D. T. Armstrong, and R. B. Gilchrist Role of Oocyte-Secreted Growth Differentiation Factor 9 in the Regulation of Mouse Cumulus Expansion Endocrinology, June 1, 2005; 146(6): 2798 - 2806. [Abstract] [Full Text] [PDF]
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J. Yang, S. Medvedev, J. Yu, L. C. Tang, J. E. Agno, M. M. Matzuk, R. M. Schultz, and N. B. Hecht Absence of the DNA-/RNA-binding protein MSY2 results in male and female infertility PNAS, April 19, 2005; 102(16): 5755 - 5760. [Abstract] [Full Text] [PDF]
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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]
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K. P McNatty, J. L Juengel, K. L Reader, S. Lun, S. Myllymaa, S. B Lawrence, A. Western, M. F Meerasahib, D. G Mottershead, N. P Groome, et al. Bone morphogenetic protein 15 and growth differentiation factor 9 co-operate to regulate granulosa cell function Reproduction, April 1, 2005; 129(4): 473 - 480. [Abstract] [Full Text] [PDF]
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K. P McNatty, J. L Juengel, K. L Reader, S. Lun, S. Myllymaa, S. B Lawrence, A. Western, M. F Meerasahib, D. G Mottershead, N. P Groome, et al. Bone morphogenetic protein 15 and growth differentiation factor 9 co-operate to regulate granulosa cell function in ruminants Reproduction, April 1, 2005; 129(4): 481 - 487. [Abstract] [Full Text] [PDF]
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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]
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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]
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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]
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L.J. McKenzie, S.A. Pangas, S.A. Carson, E. Kovanci, P. Cisneros, J.E. Buster, P. Amato, and M.M. Matzuk Human cumulus granulosa cell gene expression: a predictor of fertilization and embryo selection in women undergoing IVF Hum. Reprod., December 1, 2004; 19(12): 2869 - 2874. [Abstract] [Full Text] [PDF]
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M. Donnison and P. L. Pfeffer Isolation of Genes Associated with Developmentally Competent Bovine Oocytes and Quantitation of Their Levels During Development Biol Reprod, December 1, 2004; 71(6): 1813 - 1821. [Abstract] [Full Text] [PDF]
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G. A. R. Maciel, E. C. Baracat, J. A. Benda, S. M. Markham, K. Hensinger, R. J. Chang, and G. F. Erickson Stockpiling of Transitional and Classic Primary Follicles in Ovaries of Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5321 - 5327. [Abstract] [Full Text] [PDF]
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K P McNatty, L G Moore, N L Hudson, L D Quirke, S B Lawrence, K Reader, J P Hanrahan, P Smith, N P Groome, M Laitinen, et al. The oocyte and its role in regulating ovulation rate: a new paradigm in reproductive biology Reproduction, October 1, 2004; 128(4): 379 - 386. [Abstract] [Full Text] [PDF]
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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]
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D. Tomic, K. P. Miller, H. A. Kenny, T. K. Woodruff, P. Hoyer, and J. A. Flaws Ovarian Follicle Development Requires Smad3 Mol. Endocrinol., September 1, 2004; 18(9): 2224 - 2240. [Abstract] [Full Text] [PDF]
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R.B. Gilchrist, L.J. Ritter, M. Cranfield, L.A. Jeffery, F. Amato, S.J. Scott, S. Myllymaa, N. Kaivo-Oja, H. Lankinen, D.G. Mottershead, et al. Immunoneutralization of Growth Differentiation Factor 9 Reveals It Partially Accounts for Mouse Oocyte Mitogenic Activity Biol Reprod, September 1, 2004; 71(3): 732 - 739. [Abstract] [Full Text] [PDF]
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S. Sudo, O. Avsian-Kretchmer, L. S. Wang, and A. J. W. Hsueh Protein Related to DAN and Cerberus Is a Bone Morphogenetic Protein Antagonist That Participates in Ovarian Paracrine Regulation J. Biol. Chem., May 28, 2004; 279(22): 23134 - 23141. [Abstract] [Full Text] [PDF]
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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]
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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]
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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]
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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]
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D. Mukhopadhyay, A. Asari, M. S. Rugg, A. J. Day, and C. Fulop Specificity of the Tumor Necrosis Factor-induced Protein 6-mediated Heavy Chain Transfer from Inter-{alpha}-trypsin Inhibitor to Hyaluronan: IMPLICATIONS FOR THE ASSEMBLY OF THE CUMULUS EXTRACELLULAR MATRIX J. Biol. Chem., March 19, 2004; 279(12): 11119 - 11128. [Abstract] [Full Text] [PDF]
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J. L. Juengel, N. L. Hudson, L. Whiting, and K. P. McNatty Effects of Immunization Against Bone Morphogenetic Protein 15 and Growth Differentiation Factor 9 on Ovulation Rate, Fertilization, and Pregnancy in Ewes Biol Reprod, March 1, 2004; 70(3): 557 - 561. [Abstract] [Full Text] [PDF]
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D. Schmidt, C. E. Ovitt, K. Anlag, S. Fehsenfeld, L. Gredsted, A.-C. Treier, and M. Treier The murine winged-helix transcription factor Foxl2 is required for granulosa cell differentiation and ovary maintenance Development, February 15, 2004; 131(4): 933 - 942. [Abstract] [Full Text] [PDF]
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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]
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