Dec. 2011 Journal of Northeast Agricultural University (English Edition) Vol. 18No.

484-87

Insulin-like Growth Factor-I (IGF-I) in Reproduction System of Female

Bovine

QI Meiyu1, 2, Zvi Roth3, and LIU Di1, 2*

1
College of Animal Sciences and Technology, Northeast Agricultural University, Harbin 150030, China
2
Institute of Animal Husbandry, Heilongjiang Academy of Agricultural Sciences, Harbin 150086, China
3
Department of Animal Sciences, Faculty of Agriculture, Food and Environmental Quality Sciences, Hebrew University of Jerusalem, Rehovot 76100,
Israel

Abstract˖Insulin-like growth factor-I (IGF-I) plays a key role in female reproduction, because it has the effect of anti-apoptosis,
improving cell proliferation, transformation and differentiation. This paper reviewed the effects of IGF-I on ovary, follicle growth,
acquisition of oocyte competence and preimplantation embryo viability, and then summarized different points about IGF-I for
reproduction system.
Key words˖IGF-I, bovine, reproduction system, ovary, follicle, oocyte, preimplantation embryo
CLC number: S823; Q813 Document code: A Article ID: 1006-8104(2011)-04-0084-04

Introduction Effects of IGF-I on Ovary

Insulin-like growth factor (IGF) system includes IGF-I
and its receptor IGF-IR, IGF-II and its receptor IGF-
IIR, IGF binding proteins (IGFBPs) and IGF proteases.
IGFs are single-chain polypeptides with structural
homology to pro-insulin. IGF-I and IGF-II act on a
variety of mammalian cells in an endocrine, paracrine
[1-2]
and autocrine manner regulating cell prolifera-
[3-5]
tion, apoptosis, transformation and differentiation
However, to some extent, they exert different effects in
different tissues by different ways. IGF-II is expressed
more widely by the embryo, where it is required for
the normal embryonic development. The central role
of IGF-I in regulating postnatal growth and mediating
growth-promoting effects of GH has also been con-
[6]
firmed .
Various actions of IGF-I and insulin have been
demonstrated in the ovary, including enhancement of
cell proliferation, aromatase activity and progesterone
biosynthesis. In several mammalian species, IGF-I
has been shown to stimulate both proliferation and
differentiation of granulosa cells, and to support these
cells' survival by increasing their resistance to apopto-
. sis [7]. IGF-1 stimulates proliferation of granulosa
cells in small follicles, and regulates human luteal
steroidogenesis by increasing progesterone level and
estradiol production. IGF-I is regarded as a cogo-
nadotropin with LH in stimulating steroidogenesis
in theca-interna cells. The presence of IGF-I and the
growth factors TGFb2, bFGF and EGF-R in develop-
ing ovaries suggests that growth factors play an im-

Received 22 March 2010

QI Meiyu (1978-), female, research associate, Ph. D candidate, engaged in the research of embryo engineering.
* Corresponding author. LIU Di, professor, supervisor of Ph. D student, engaged in the research of animal genetic, breeding and reproduction. E-mail:
liudi1963@163.com

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QI Meiyu et al. Insulin-like Growth Factor-I (IGF-I) in Reproduction System of Female Bovine
portant role in ovarian function[8].
Effects of IGF-I on Follicle Develop-
ment
IGF-I is involved in the regulation of ovarian folli-
cular development and its role during folliculogenesis
has been extensively studied in mammals. The in-
volvement of IGF-I in follicular development is sug-
gested by the presence of IGF-IR and IGF-I mRNA
in the ovary. IGF-I-knockout mice are infertile due to
their ovarian follicles' inability to grow at the antral
stage and proceed to ovulation[9]. In cattle, IGF is im-
portant at the antral stage of follicular development,
when it is involved in the regulation of follicle growth,
stimulation of somatic cell proliferation, and biosyn-
thesis of estrogen and progesterone. Recent work has
outlined the beneficial effects of IGF-I at the early
follicle growth and its role in inducing antrum forma-
[10-11]
tion and promoting primordial follicle activition
Effects of IGF-I on Oocytes
Oocyte quality is a prerequisite for successful embryo-
nic development. During oogenesis, many changes
occur at the cellular and molecular levels which enable
oocytes to undergo meiosis, monospermic fertilization,
and transition through the early developmental stages
until embryonic genome activation. It is believed
that the discrepancy between the numbers of oocytes
fertilization and embryos development to the blastocyst
stage is mainly due to the low developmental potential
of oocytes used for in vitro embryo production (IVP) .
Therefore, improvement of oocyte competence is a
crucial and challenging assignment for IVP which, in
and of itself, is considered as a mostly oxidative stress
condition.
 The involvement of IGF-I in oocyte development
has been confirmed by the presence of its receptors in
ovarian follicles and in immature oocytes. Wasielak
and Bogacki reported that the increase in apoptotic
DNA degeneration after oocyte recovery was reduc-
·85·
ed by the addition of IGF-I to the maturation medium,
which indicated that IGF-I might serve as an anti-
apoptotic factor during oocyte maturation[13]. Demee-
stere et al. reported a reduction in the number of
oocytes degenerating after fertilization when mice
follicles were cultured and then oocytes matured in
the presence of IGF-I[14]. Recent reports from several
laboratories supported a potential role for growth
factors in the intrafollicular control of meiosis. IGF-I
has been demonstrated to enhance nuclear maturation
in oocytes surrounded by compact cumulus cells in
both bovines[15] and humans[16]. IGF-I is also known
to stimulate maturation in Xenopus[17], rabbit[18] and
buffalo [19] oocytes. However, other studies have
reported that IGF-I did not affect oocyte maturation in
sheeps[20], cattle[21] or pigs[22]. Variable results among
studies might be due to the long and complex process
of oocyte maturation in vitro, which has not been
completely elucidated yet. The mechanism by which
. IGF-I affects oocyte development is still not clear.
Effects of IGF-I on Preimplantation
Embryos
The in vitro culture environment has great influence
on the development and quality of embryos. A positive
effect of IGF-I on embryogenesis was shown when
embryos were cultured with this growth factor at
concentration ranging from 10 to 200 ng • mL-1[5, 23-25].
IGF-I's effects were prominently characterized by
decreased apoptosis and increased cell proliferation.
  Although the mechanism of IGF-I action on in-
[12]
vitro-cultured embryos is not clear, it is well known
that IGF-I mediates preimplantation embryo develop-
ment by high affinity to IGF-IRs. Matsui et al. re-
ported that an anti-IGF-IR antibody (uIR-3) in the
embryo culture medium completely blocked the sti-
mulation of development to the morula stage by in-
sulin and IGF-I, suggesting that this stimulation was
mediated through IGF-IR[23]. In mice, mutations in
IGF-I and IGF-IR resulted in developmental retarda-
tion and neonatal lethality[26]. IGF-I stimulated oocyte
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·86· Journal of Northeast Agricultural University (English Edition) Vol. 18No. 42011

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. In addition, IGF-I supple- 3 Leng S L, Leeding K S, Whitehead R H, et al. Insulin-like growth

mented to the culture medium significantly increased factor (IGF)-binding protein-6 inhibits IGF-II-induced but not basal

the proportion of embryos development to the blasto- proliferation and adhesion of LIM 1215 colon cancer cells [J].

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mass in human blastocysts[27]. IGF-I not only increased 4 Moschos S J, Mantzoros C S. The role of the IGF system in

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percentage of apoptotic cells. Makarevich and Markkula Oncology, 2002, 63(4): 317- 332.

reported that the addition of IGF-I to culture media, 5 Makarevich AV, Markkula M. Apoptosis and cell proliferation

but not maturation media, increased the total cell num- potential of bovine embryos stimulated with insulin-like growth

bers of blastocysts and lowered the apoptotic index by factor I during in vitro maturation and culture [J]. Biology of
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decreasing the numbers of apoptotic cells per embryo .
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spontaneous apoptosis in in-vitro-cultured preim- binding proteins: biological actions [J]. Endocrine Reviews, 1995,

plantation embryos, but also blocked apoptosis in- 16(1): 3-34.

duced by exogenous factors. IGF-I blocked the induc- 7 Mazerbourg S, Bondy C A, Zhou J, et al. The insulin-like growth

tion of apoptosis in bovine embryos exposed to heat factor system: a key determinant role in the growth and selection of

shock in vitro, suggesting a protective role against em- ovarian follicles? A comparative species study [J]. Reproduction in

bryonic stressors[28]. Similarly, IGF-I improved embryo Domestic Animals, 2003, 38(4): 247-258.

development, cell proliferation and embryo diameter 8 Ergin K, Gürsoy E, Başimoğlu Koca Y, et al. Immunohistochemical
[25] detection of insulin-like growth factor-I, transforming growth
in rabbit embryos exposed to UV radiation . In mouse
embryos, the detrimental effects of oxidative stress factor-beta2, basic fibroblast growth factor and epidermal growth

induced by hydrogen peroxide could be alleviated by factor-receptor expression in developing rat ovary [J]. Cytokine,
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the addition of IGF-I to the culture medium .
9 Baker J, Hardy M P, Zhou J, et al. Effects of an Igf1 gene null

mutation on mouse reproduction [J]. Molecular Endocrinology,

Conclusions
1996, 10(7): 903-918.

IGF-I is an important regulatory factor in ovarian 10 Sharma G T, Dubey P K, Kumar G S. Effects of IGF-1, TGF-

function, development of follicles, oocytes and alpha plus TGF-beta1 and bFGF on in vitro survival, growth and

preimplantation embryos. It plays an important role apoptosis in FSH-stimulated buffalo (Bubalis bubalus) preantral

in these aspacts by its anti-apoptosis and improves follicles [J]. Growth Hormone & IGF Research, 2010, 20(4):

cell proliferation, transformation and differentiation. 319-325.

However, further research needs studying the mech- 11 Martins F S, Celestino J J, Saraiva M V, et al. Interaction between

nisms involved in all these processes.   growth differentiation factor, insulin-like growth factor I and

growth hormone on the in vitro development and survival of goat

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