Dose-response study of intrafollicular injection of insulin-like growth factor-I on follicular fluid factors and follicle dominance in mares.
Ginther OJ,et aal .
The effect of insulin-like growth factor-I (IGF-I) on the concentrations of follicular fluid factors during follicle deviation and the development of dominance was studied in mares in two experiments. Transvaginal ultrasound guidance was used for intrafollicular injection and subsequent sequential sampling of follicular fluid. Treatment involved a single injection of IGF-I into the second-largest follicle (F2) at the expected beginning of deviation (Hour 0) based on diameter (>/=20 mm) of the largest follicle (F1). Mares in IGF-I groups were given a dose of 500 microg (experiment 1) or 250, 25, or 2.5 microg (experiment 2). Ablation of F1 at Hour 24 was done in experiment 1, but not in experiment 2. The 500- and 250-microg doses stimulated growth, leading to ovulation of F2 in 10 of 10 and 4 of 5 mares in the two experiments, respectively, compared to 4 of 12 and 0 of 5 in saline-injected controls. These doses prevented (P < 0.05) the increase in IGF binding protein-2 and androstenedione that occurred in F2 of controls and increased (P < 0.05) the concentrations of activin-A, inhibin-A, and vascular endothelial growth factor (VEGF). The 500-microg dose stimulated higher (P < 0.05) concentrations of estradiol, but not until Hour 48, whereas the lower doses were ineffective. In experiment 2, free IGF-I concentrations in F2 at Hour 24 decreased progressively as the dose decreased so that concentrations for the 2.5-microg dose were higher (P < 0.05) than in F2 of controls and similar (not significantly different) to endogenous concentrations in F1. Correspondingly, concentrations of androstenedione in F2 at Hour 24 were lower (P < 0.05) and concentrations of activin-A, inhibin-A, and VEGF were higher (P < 0.05) after treatment of F2 with the 2.5-microg dose than in F2 of controls and were similar to concentrations in F1. Hence, a physiologic intrafollicular dose of IGF-I did not stimulate estradiol production but reduced the production of androstenedione and stimulated the production of activin-A, inhibin-A, and VEGF during follicle selection in mares.
Oropeza A, et al reported the improvement of the Developmental Capacity of Oocytes from Prepubertal Cattle by Intraovarian Insulin-Like Growth Factor-I Application.
The developmental potential of oocytes from prepubertal cattle is decreased compared to those from their adult counterparts. The aim of the present study was to improve the developmental capacity of oocytes from prepubertal cattle by either systemic application of rbST or intraovarian injection of IGF-I. Blastocyst yields and the mRNA expression pattern (relative abundance, RA) of three putative marker genes (i.e. glucose transporter-1, Glut-1; eukaryotic translation initiation factor-1A, eIF1A and upstream binding factor, UBF) were selected as criteria to determine the success of the treatments. At 6-7 months of age, thirty healthy Holstein calves were randomly assigned to three experimental groups. The first group served as control and received an intraovarian injection of 0.6 ml acetic acid. The second group received a single s.c. injection of 500 mg of somatotropin (rbST). The third group received an intraovarian injection of 6 micro g rhIGF-I. During the following two weeks, follicles were aspirated 4 times via transvaginal ultrasound-guided technology. All animals were i.m. injected with 60 mg FSH 48 h prior to each aspiration. The treatments were repeated with the same animals at 9-10, 11-12 and 14-15 months of age. For comparison, five adult cows were i.m. injected each with 100 mg FSH and underwent oocyte retrieval. The proportion of oocytes considered to be developmentally competent was higher in cows than in calves (65% vs. 58%, 50%, 52%) for the control, rbST and IGF-I groups, respectively. The rate of blastocysts was similar in IGF-I treated calves and cows (28% and 25%) and was higher (P = 0.05) than in the controls and the rbST group (11% and 16%). The RA for Glut-1 was lower (P = 0.05) in 2-4-cell embryos from calves compared to cows. At the 8-16-cell stage Glut-1 RA was similar in IGF-I treated calves and cows. The RA for eIF1A was higher (P = 0.05) in 8-16 cells embryos derived from cows than those from the control group. Results show that IGF-I intraovarian injection increased blastocyst yields and mRNA expression of Glut-1 and eIF1A to levels found in embryos produced from adult cows. This treatment may at least partially overcome the developmental deficiency of oocytes derived from calves and could be a step forward towards the use of prepubertal animals in breeding programs aimed at shortening the generation interval.
Extracellular Matrix, Secreted
Follicle development, Preantral follicle growth, Antral follicle growth, Follicle atresia, Steroid metabolism, Early embryo development
Stimulation of the largest subordinate follicle by intrafollicular treatment with insulin-like growth factor 1 is associated with inhibition of the dominant follicle in heifers. Shahiduzzaman AK et al. The effect of intrafollicular treatment of the second-largest follicle (F2) with insulin-like growth factor (IGF) 1 on the largest follicle (F1) and F2 was studied in heifers. Treatment of F2 was done when F1 reached >/=8.2 mm (expected beginning of follicle deviation; Day 0 or Hour 0). In each of two experiments, three groups (n = 6 or 7 heifers/group) were used: controls, F2 treated with vehicle and F2 treated with IGF1. The IGF1 treatment consisted of 200 mug of recombinant human IGF1 (pharmacological dose) in 20 muL of vehicle. In Experiment 1, the hypothesis that treatment of F2 with IGF1 has a stimulatory effect on F2 was supported by a greater (P < 0.05) incidence of F2 dominance (>/=10 mm) in the IGF1 group (71%) than in the other two groups (8%), and a greater (P < 0.02) growth rate of F2 on Days 0-2. Unexpectedly, treatment of F2 with IGF1 had an inhibitory effect on F1, as indicated by a reduced (P < 0.03) growth rate of F1 during Days 0-1 and Days 0-4 and a lesser (P < 0.05) maximum diameter of F1 in the IGF1 group. In Experiment 2, the hypothesis of an inhibitory effect on F1 when F2 was treated with IGF1 was supported by a lesser (P < 0.04) increase in diameter of F1 and a lesser (P < 0.04) percentage of follicle wall with power-Doppler signals of blood flow between Hours 0 and 14 in the IGF1 group. Circulating concentrations of FSH and LH were not altered significantly in either experiment. In conclusion, treatment of F2 with IGF1 at the expected beginning of deviation had a stimulatory effect on F2, but an inhibitory effect on F1.
Adashi EY reviewed the literature on IGF system in the ovary. The large body of information now supports the existence of an intraovarian IGF system replete with ligands, receptors, and binding proteins. The intraovarian IGF system is most likely concerned with the amplification of gonadotropin hormonal action, other potential regulatory roles remaining speculative at this time. There is every reason to believe that work in this area in the upcoming several years will yield new insight necessary to establish whether or not IGFs are truly indispensable to ovarian function.Spicer LJ, et al 2000 studied effects of intraovarian infusion of insulin-like growth
factor-I on ovarian follicular function in cattle.
Fourteen cycling Holstein
cows were divided equally into two groups: Control, osmotic minipumps
(containing vehicle) surgically inserted into each ovary, or IGF-I treated,
osmotic minipumps as in Controls but pumping 2.0 mu g of recombinant human
IGF-I per hr for 7 days. Intraovarian IGF-I
infusion increased concentrations of IGF-I in follicular fluid of small but
not large follicles on Day 7 of treatment. Total ovarian weight (26.4 +/- 2.6
g), and size of the second largest (9.1 +/- 0.2 mm) follicle did not differ (P
> 0.10) between control and IGF-I-treated cows. Size of the largest follicle
was increased (P < 0.10) in IGF-I-treated versus control cows.
IGF-I treatment increased (P < 0.05) estradiol concentrations in follicular
fluid of small follicles, but had no effect (P < 0.10) on estradiol
concentrations in follicular fluid of large follicles, or on progesterone,
androstenedione, or IGF binding protein concentrations in small or large
follicles. It was concluded that a 7-day infusion of IGF-I directly into the stroma
of the ovary altered follicular growth and follicular fluid estradiol
Expression of IGFs and their receptors is a potential marker for embryo quality. Liu HC et al. PROBLEM: Insulin-like growth factors (IGFs) and insulin have been demonstrated to stimulate oocyte maturation and embryo development. Therefore, the expression of IGFs and their receptors may be an important intrinsic factor for embryo growth and may be a potential marker for embryo quality. METHOD OF STUDY: Thirty donated day 3 embryos were cultured in vitro for an additional 3 days to observe their developmental potential and were semiquantitatively analyzed for the expression of IGF-I, IGF-II, IGF-IR, IGF-IIR, and insulin-R. RESULTS: Our results show that the activity of these gene expressions correlates well with the morphological assessment and that high and more gene expressions were often associated with embryos of high growth potential. CONCLUSION: The IGF system may indeed play an important role in human embryogenesis; IGF gene expressions can be a good indicator of embryonic developmental stage and/or growth potential; finally, the IGF system can serve as a marker for embryo quality.
Effect of IGF-I on pig oocyte maturation, fertilization, and early embryonic development in vitro, and on granulosa and cumulus cell biosynthetic activity. Xia P et al. Porcine granulosa cells have been shown previously to both secrete and respond to insulin-like growth factor-I (IGF-I), suggesting an autocrine function of this peptide in the follicle. The present work was undertaken to determine possible effects of IGF-I on in vitro maturation, in vitro fertilization, and early embryonic development in culture. Granulosa and cumulus cell proliferation and differentiation based on 3H-thymidine uptake and progesterone production, respectively, were also assessed. The results showed that the cleavage rate of oocytes was markedly stimulated in a dose-dependent manner by the addition of IGF-I to the oocyte maturation medium (P < 0.05). Embryo development beyond the 8-cell stage was improved by IGF-I, reaching a maximum of 22% at 200 ng/ml IGF-I. Treatment with IGF-I after fertilization increased the percentage of total oocyte cleavage (P < 0.05) to approximately 52%, 43%, and 57% at, respectively, 25, 50, and 100 ng/ml IGF-I. 3H-thymidine incorporation by granulosa cells was significantly increased in cultures treated with FSH (3-fold) or IGF-I (6-fold) compared to the control. For the cumulus cells, FSH caused a similar increase (3-fold) in 3H-thymidine incorporation while IGF-I stimulated a 15-fold increase. Progesterone production by the granulosa cells was increased to the same extent by treatment with FSH or IGF-I (4.7 and 5.1-fold, respectively). However, for the cumulus cells, while FSH caused a marked 16-fold increase in progesterone production, IGF-I caused only a marginal increase of 2.5-fold.(ABSTRACT TRUNCATED AT 250 WORDS)
Expression regulated by
FSH, LH, Steroids, Growth Factors/ cytokines
Granulosa, Theca, Luteal cells
Secondary, Antral, Preovulatory, Corpus luteum
Mutation name: None
type: null mutation fertility: subfertile Comment: Transgenic mice with a homozygous defect of the Igf1 gene (IGF-I knockout mice) have profound embryonic and postnatal growth retardation (Liu et al., 1993 ; [Baker et al., 1993$ 8402902]; [Powell-Braxton et al., 1993 $ 8276243]).
Mutation name: None
type: naturally occurring fertility: unknown Comment:Woods et al. (1996) described a 15-year-old boy with severe prenatal and postnatal growth failure, sensorineural deafness, and mental retardation who was homozygous for a partial deletion of the IGF1 gene. The patient had been delivered at 37 weeks' gestation by cesarean section because of poor fetal growth. He showed symmetric growth retardation with a birth weight of 1.4 kg, length of 37.8 cm, and head circumference of 27 cm.