• Korean Journal of Animal Reproduction
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• v.25 no.1
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• pp.71-77
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• 2001

This experiment was designed to improve the production efficiency of germ-line chimeric mice from phospholipase C (PLC)-$\beta$3 or peroxiredoxin (Prx) E -targeted ($\Delta$) ES cells by the investigating the manipulation conditions and characteristics of Jl ES cells. Four targeting clones were isolated to investigate the karyotypical and morphological stability prior to injection. All clones ($\Delta$PLC$\beta$-3 C3, $\Delta$Prx II C3, C10 and I5) showed more than 80% euploidism, however, most of $\Delta$PLC$\beta$-3 C3 clones were extensively differentiated compared to the other clones. Nine of 13 $\Delta$Prx II chimeras appeared to have at least 80% chimerism, whereas $\Delta$PLC$\beta$-3 C3 chimeras had 20% chimerism at most. Therefore, the morphological stability of ES cells under stable euploidism might mainly affect the production rate of high-coat chimeric mice. To increase the collection rate of injectable blastocysts (IBs), 5 to 10 week -aged C57BL/6J female mice were sacrificed at 3.5 days post-coitum. Ten week-aged mice were the most optimal IB donors by showing the highest collection rate (2.94/mouse) of injectable blastocysts without increase of non-injectable embryos (0.29/mouse). Foster mothers might be another factor because ICR x C57BL/6J F1 foster mother showed more increased productivity in litter size (2.8 vs. 5.6) and chimera (0 vs. 35.3%) than those of ICR foster mothers. In conclusion, the efficient production of germ-line chimeras mainly depends on the maintenance of ES cell morphology during targeting procedure, and the establishment of manipulation conditions might be a key point to maximize it.

• Korean Journal of Ichthyology
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• v.35 no.2
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• pp.91-100
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• 2023

The early life history of Silurus microdorsalis living in Jahocheon Stream was studied by observing egg and morphological development. Live fish were captured in June 2018, then reared in a circulating filtration system under a 14L : 10D photoperiod with a water temperature of 18℃. To artificially induce spawning, females were injected with 0.5 mL of Ovaprim (Syndel, Nanaimo, BC, Canada) per kg of body weight, and males were injected with 10,000 IU/kg body weight of human chorionic gonadotropin. Approximately 15 h later, eggs were artificially inseminated by the dry method. Mature eggs were light pale yellow, which separated them from immature eggs. Fertilized eggs were 2.16±0.06 mm (n=8) in diameter and fully hatched at 181 h after fertilization. The fertilization rate was 63.1±2.2%, and 10.0±3.7% of the embryos were malformed at 18℃. The rates of development were 181 h at 18℃, 109 h at 21℃, and 76 h at 24℃. The larval size immediately after hatching was 4.64±0.22 mm (n=8), and the larvae displayed negative phototaxis at 1 day after hatching. The total larval length on 7 days after hatching was 12.47±0.53 mm, with 25~30 basal anal fin rays and 14~16 basal caudal fin rays observed. The total larval length was 14.13±0.51 mm on 9 days after hatching, and approximately 90% of the black endoplasmic reticulum was deposited on the head and body. The dorsal fin had formed, and a single basal body was observed. On 15 days after hatching, the total larval length was 16.69±0.31 mm; the number of basal caudal fin rays (18 poles) was an integer because 2 dorsal fin basal rays and 60~63 anal fin basal rays were observed. The total larval length was 28.96±1.10 mm on 50 days after hatching; the numbers of caudal fins (n=18), dorsal fins (n=3), pectoral fins (n=11), and anal fin basal rays (n=67~73) were integers.

• Journal of Nutrition and Health
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• v.56 no.6
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• pp.602-614
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• 2023

Purpose: The balance between synthesis and degradation of proteins plays a critical role in the maintenance of skeletal muscle mass. Mitochondrial dysfunction has been closely associated with skeletal muscle atrophy caused by aging, cancer, and chemotherapy. Polygalacin D is a saponin derivative isolated from Platycodon grandiflorum (Jacq.) A. DC. This study aimed to investigate the effects of polygalacin D on myoblast differentiation and muscle atrophy in association with mitochondrial function in in vitro and in zebrafish models in vivo. Methods: C2C12 myoblasts were cultured in differentiation media containing different concentrations of polygalacin D, followed by the immunostaining of the myotubes with myosin heavy chain (MHC). The mRNA expression of markers related to myogenesis, muscle atrophy, and mitochondrial function was determined by real-time quantitative reverse transcription polymerase chain reaction. Wild type AB^* zebrafish (Danio rerio) embryos were treated with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) with or without polygalacin D, and immunostained to detect slow and fast types of muscle fibers. The Tg(Xla.Eef1a1:mitoEGFP) zebrafish expressing mitochondria-targeted green fluorescent protein was used to monitor mitochondrial morphology. Results: The exposure of C2C12 myotubes to 0.1 ng/mL of polygalacin D increased the formation of MHC-positive multinucleated myotubes (≥ 8 nuclei) compared with the control. Polygalacin D significantly increased the expression of MHC isoforms (Myh1, Myh2, Myh4, and Myh7) involved in myoblast differentiation while it decreased the expression of atrophic markers including muscle RING-finger protein-1 (MuRF1), mothers against decapentaplegic homolog (Smad)2, and Smad3. In addition, polygalacin D promoted peroxisome proliferator-activated receptor-gamma coactivator (Pgc1α) expression and reduced the level of mitochondrial fission regulators such as dynamin-1-like protein (Drp1) and mitochondrial fission 1 (Fis1). In a zebrafish model of FOLFIRI-induced muscle atrophy, polygalacin D improved not only mitochondrial dysfunction but also slow and fast muscle fiber atrophy. Conclusion: These results demonstrated that polygalacin D promotes myogenesis and alleviates chemotherapy-induced muscle atrophy by improving mitochondrial function. Thus, polygalacin D could be useful as nutrition support to prevent and ameliorate muscle wasting and weakness.

• Reproductive and Developmental Biology
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• v.28 no.3
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• pp.181-185
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• 2004

This study was conducted to examine whether activation treatments, source of oocytes and culture conditions affect in vitro developmental ability of caprine oocytes. Mature Korean native goats were pretreated with intravaginal CIDR for 10 days. The goats were then treated with a single intramuscular injection of 1,000 IU PMSG on Day 8 or twice daily injection of a total of 70 mg FSH for 3 days from Day 8 of CIDR insertion for superovulation. All the goats were injected with 10 mg PGF/sub 2a/ on Day 8 and 400 IU hCG on Day 10 of CIDR. Oocytes were surgically collected by oviduct flushing(in vivo maturation) or direct follicle aspiration(in vitro maturation) through mid-ventral incision at 35 h after hCG injection. Fifteen to twenty oocytes were placed in TCM-199 medium containing 25 mM Hepes and hormones under mineral oil at 39℃ in a humudified atmosphere of 5% CO₂ in air for 22 to 24 h. After maturation, the oocytes were activated by electric stimulation or ionomycin + 6-DMAP. The activated oocytes were then cultured in M16, TCM-199 and mSOF media supplemented with proteins at 39℃ for 6 to 7 days. Activation treatments did not affect cleavage of the oocytes. The cleavage rates were 64.1% (41/64) in oocytes activated by electric stimulation and 76.5% (218/285) in oocytes activated by ionomycin + 6-DMAP. The proportion of development to blastocyst was 15.6% (34/218) in oocytes activated by ionomycin + 6-DMAP, but activation by electric stimulation did not support embryos developed beyond morula stage. There were no differences in the cleavage rates of activated oocytes experiencing in vivo (86.8%, 66/76) and in vitro maturation (69.0%, 127/184). However, the development rate to blastocyst stage was significantly (P<0.05) higher for oocytes matured in vivo (50.0%, 33/66) compared to in vitro (0.8%, 1/127). Culture conditions did not affect the cleavage of -activated oocytes. The cleavage rates were 51.6% (49/95) in M16, 64.3% (18/28) in TCM-199 and 81.0% (145/179) in mSOF, respectively. By contrast, the development rate of activated oocytes to stage was greater (P<0.05) for oocytes cultured in mSOF medium (23.4%, 34/145) than in M16 or TCM-199 (0.0%). Our results suggest that source of oocytes and culture conditions are major factors affecting in vitro development of caprine parthenogenetic oocytes.

• Korean Journal of Animal Reproduction
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• v.26 no.1
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• pp.17-23
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• 2002

The present study was carried out to investigate the effects of the maturation media such as a modified TCM-199 (mTCM-199) medium, modified Waymouth MB 752/1 (mWaymouth MB 752/1) medium or NCSU-23 medium on penetrability of pig oocytes by liquid boar sperm. Oocytes (30~40) were transferred into each well of a Nunc 4-well multidish containing 0.5 $m\ell$ maturation medium. When immature pig oocytes were cultured in mTCM-199, mWaymouth MB 752/1 and NCSU-23 maturation media for 44 h in 5% $CO_2$, in air at 38.5$^{\circ}C$, the germinal vesicle breakdown (CVBD) rates of the oocytes were 95.6, 94.1 and 94.9%, respectively, and the maturation rates (metaphase II) of oocytes were 92.5, 90.1 and 91.1%, respectively. No differences were observed among the maturation media. The spermrich portion of ejaculates with greater than 90% motile sperm were used in the experiment. The semen was cooled 22 to 24$^{\circ}C$ over 2 h period. The semen was diluted with Beltsville Thawing Solution (BTS) extender at room temperature to give 2$\times$10$^{8}$ sperm/$m\ell$ in 100 $m\ell$ plastic bottle. Liquid boar semen of 30 $m\ell$ in 100 $m\ell$ plastic bottle was kept at 17$^{\circ}C$ for 5 days. The sperm with greater than 70% motility after day 5 of storage were used for in-vitro fertilization (IVF). After 44 h maturation of immature oocytes, cumulus cells were removed and oocytes (30~40) coincubated far 6 h in 0.5 $m\ell$ mTCM-199 and mTBM fertilization media with 2$\times$1061$m\ell$ sperm concentration. At 6 h after IVF, oocytes were transferred into 0.5 $m\ell$ mTCM-199 and NCSU-23 culture media for further culture 6 or 42 h. Sperm penetration, polyspermy and male pronuclear formation of oocytes at 12 h after IVF, and developmental ability of oocytes at 48 h after IVF were evaluated. The oocytes in combination with NCSU-23 medium for maturation and mTBM medium for IVF increased male pronuclear formation (48.0%) compared to those in combination with mTCM-199 media for maturation and IVF, and mWaymouth MB 752il medium for maturation and mTCM-199 medium far IVF. The rates of cleaved embryos (2~4 cell stage) at 48 h after IVF were 24.1% in combination with mTCM-199 media for maturation, IVF and culture, 43.6% in combination with mWaymouth MB 75211 medium fur maturation and mTCM-199 media for IVF and culture, and 71.2% in combination with NCSU-23 medium for maturation, mTBM medium for IVF and NCSU-23 medium for culture. In conclusion, we found out the oocytes matured in vitro were fertilized by liquid boar sperm stored in BTS extender at 17$^{\circ}C$ for 5 days. We recommend the simple defined NCSU-23 medium for nuclear maturation, mTBM medium and liquid boar sperm for IVF, and NCSU-23 medium for embryo culture.

• Journal of Genetic Medicine
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• v.7 no.2
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• pp.125-132
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• 2010

Purpose: Preimplantation genetic diagnosis (PGD), also known as embryo screening, is a pre-pregnancy technique used to identify genetic defects in embryos created through in vitro fertilization. PGD is considered a means of prenatal diagnosis of genetic abnormalities. PGD is used when one or both genetic parents has a known genetic abnormality; testing is performed on an embryo to determine if it also carries the genetic abnormality. The main advantage of PGD is the avoidance of selective pregnancy termination as it imparts a high likelihood that the baby will be free of the disease under consideration. The application of PGD to genetic practices, reproductive medicine, and genetic counseling is becoming the key component of fertility practice because of the need to develop a custom PGD design for each couple. Materials and Methods: In this study, a survey on the contents of genetic counseling in PGD was carried out via direct contact or e-mail with the patients and specialists who had experienced PGD during the three months from February to April 2010. Results: A total of 91 persons including 60 patients, 49 of whom had a chromosomal disorder and 11 of whom had a single gene disorder, and 31 PGD specialists responded to the survey. Analysis of the survey results revealed that all respondents were well aware of the importance of genetic counseling in all steps of PGD including planning, operation, and follow-up. The patient group responded that the possibility of unexpected results (51.7%), genetic risk assessment and recurrence risk (46.7%), the reproduction options (46.7%), the procedure and limitation of PGD (43.3%) and the information of PGD technology (35.0%) should be included as a genetic counseling information. In detail, 51.7% of patients wanted to be counseled for the possibility of unexpected results and the recurrence risk, while 46.7% wanted to know their reproduction options (46.7%). Approximately 96.7% of specialists replied that a non-M.D. genetic counselor is necessary for effective and systematic genetic counseling in PGD because it is difficult for physicians to offer satisfying information to patients due to lack of counseling time and specific knowledge of the disorders. Conclusions: The information from the survey provides important insight into the overall present situation of genetic counseling for PGD in Korea. The survey results demonstrated that there is a general awareness that genetic counseling is essential for PGD, suggesting that appropriate genetic counseling may play a important role in the success of PGD. The establishment of genetic counseling guidelines for PGD may contribute to better planning and management strategies for PGD.

• Journal of Aquaculture
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• v.5 no.1
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• pp.29-67
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• 1992

Life cycle and seed production of the freshwater prawn, Macrobrachium nipponense, were studied and the results are as follows : 1. Larval development : Embryos hatched out as zoea larvae of 2.06 mm in mean body length. The larvae passed through 9 zoea stages in $15{\~}20$ days and then metamorphosed into postlarvae measuring 5.68 mm in mean body length. Each zoea stage can be identified based on the shapes of the first and second antennae, exo- and endopodites of the first and second pereiopods, telson and maxillae. 2. Environmental requirements of zoea larvae : Zoea larvae grew healthy when fed with Artemia nauplii. Metamorphosing rate was $65{\~}72{\%}$ at $26{\~}28\%$ and $7.85{\~}8.28\%_{\circ}Cl.$. The relationship between the zoeal period (Y in days) and water temperature (X in $^{\circ}C$) is expressed as Y=46.0900-0.9673X. Zoeas showed best survival in a water temperature range of $26{\~}32^{\circ}C$ (optimum temperature $28^{\circ}C$), at which the metamorphosing rate into postlarvae was $54{\~}72\%$ The zoeas survived more successfully in chlorinity range of $4.12{\~}14.08{\%_{\circ}}Cl.$, (optimum chlorinity $7.6{\~}11.6\;{\%_{\circ}}Cl.$.), at which the metamorphosing rate was $42{\~}76{\%}$. The whole zoeal stages tended to be longer in proportion as the chlorinity deviated from the optimum range and particularly toward high chlorinity. Zoeas at all stages could not tolerate in the freshwater. 3. Environmental requirements of postlarvae and juveniles : Postlarvae showed normal growth at water temperatures between $24{\~}32^{\circ}C$ (optimun temperature $26{\~}28^{\circ}$. The survival rate up to the juvenile stage was $41{\~}63{\%}$. Water temperatures below $24^{\circ}C$ and above $32^{\circ}$ resulted in lower growth, and postlarvae scarcely grew at below $17^{\circ}C$. Cannibalism tended to occur more frequently under optimum range of temperatures. The range of chlorinity for normal growth of postlarvae and juveniles was from 0.00 (freshwater) to $11.24{\%_{\circ}}Cl.$, at which the survival rate was $32{\~}35\%$. The postlarvae grew more successfully in low chlorinities, and the best growth was found at $0.00\~2.21{\%_{\circ}}Cl.$. The postlarvae and juveniles showed better growth in freshwater but did not survive in normal sea water. 4. Feeding effect of diet on zoea Ilarvae : Zoea larvae were successfully survived and metamorposed into postlarvae when fed commercial artificial plankton, rotifers, and Artemia nauplii in the aquaria. However, the zoea larvae that were fed Artemia nauplii and reared in Chlorella mixed green water showed better results. The rate of metamorphosis was $68\~{\%}75$. The larvae fed cow live powder, egg powder, and Chlorella alone did not survive. 5. Diets of postlarvae, juveniles and adults : Artemia nauplii and/or copepods were good food for postlarvae. Juveniles and adults were successfully fed fish or shellfish flesh, annelids, corn grain, pelleted feed along with viscera of domestic animals or fruits. 6. Growth of postlarvae, juveniles and adults : Under favorable conditions, postlarvae molted every five or six days and attained to the juvenile stage within two months and they reached 1.78 cm in body length and 0.17 g in body weight. The juveniles grew to 3.52 cm in body length and 1.07 g in body weight in about four months. Their sexes became determinable based on the appearance of male's rudimental processes (a secondary sex character) on the endopodites of second pereiopods of males. The males commonly reached sexual maturity in seven months after attaining the postlarvae stage and they grew to 5.65 cm in body length and 3.41 g in body weight. Whereas the females attained sexual maturity within six to seven months, when they measured 4.93 cm in body length and 2.43 g in body weight. Nine or ten months after hatching, the males grew $6.62{\~}7.14$ cm in body length and $6.68{\~}8.36$ g in body weight, while females became $5.58{\~}6.08$ cm and $4.04{\~}5.54$ g. 7. Stocking density : The maximum stocking density in aquaria for successful survival and growth was $60{\~}100$ individuals/$\ell$ for zoeas in 30-days rearing (survival rate to postlarvae, $73{\~}80{\%}$) ; $100{\~}300$ individuals/$m^2$ for postlarvae of 0.57 cm in body length (survival rate for 120 days, $78{\~}85{\%}$) ; $40{\~}60$ individuals/$m^2$ for juveniles of 2.72 cm in body length (survival rate for 120 days, $63{\~}90{\%}$) : $20{\~}40$ individuals/$m^2$ for young prawns of 5.2 cm in body length (survival rate for 120 days, $62\~90{\%}$) ; and $10\~30$ individuals/$m^2$ for adults of 6.1 cm in body length (survival rate for 60 days, $73\~100{\%}$). The stocking density of juveniles, youngs and adults could be increased up to twice by providing shelters.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.2 no.2
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• pp.147-154
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• 1969

The larvae of the ark shell Anadare broughtoni(Schrenck) were grown at room temporature (approximately $20.4^{\circ}C$), and fed laboratory-cultured Cyclotella nana. The egg of the ark shell produced in the laboratory measured about $54.9\mu$ in diameter. The embryos gradually developed into larvae up to $110.8\mu$ shell length, $83.9\mu$ shell height and with shell breadth of $58.2\mu$ even in the absence of the algal food. Beyond this sire, however, the growth of the larvae was considerably retarded. The larvae showed better growth rate when they were fed the algal food two days after spawning, i. e., early straight-hinge stage. Daily rate of food consumption varies according to the larval sizes. But the rate increases considerably when the larvae begin to form umbos. In general the rate Is indicated by the following formula: $Y=0.0025161\;X^{2.76459}$. The growth experiments of the larvae indicate that the efficiency of food conversion was higher when fed centrifuged food. Regarding to the difference in the slopes of growth curve, centrifuged food showed better growth rate as compared to those grown with the non-centrifuged food. The smaller the larval size, the greater will be the difference in growth. The larvae began settling when they reathed 261.7 to $289.6\;{\mu}$ in shell length, 199.2 to $221.7\mu$ in shell height and 147.6 to $170.8\mu$ in shell breadth. The time which elapsed from spawning to the larval settlement was about 28 days. The mean growth of the larvae is indicated with regression line and exponential curve equations as follows. Regression line shell length. 94.3 to $133.9\mu$ : Y==85.22857+3.35000X 141.6 to $269.3\mu$: Y=10.83036X-36.05357 296.8 to $373.2\mu$ : Y=19.10000X-279.30000 shell height: 72.7 to $89.7\mu$ : Y=67.11429+2.15714X 108.4 to $206.4\mu$ : Y=8.31607X-27.45357 228.6 to $282.1\mu$: Y=173.46700+13.37500X shell breadth: 45.3 to $77.8\mu$ : Y=38.08510X+2.73570X 87.4 to $157.7\mu$: Y=5.77320X-5.99640 175.4 to $214.0\mu$: Y=19.65000X-114.13300 Exponential curve shell length. 94.3 to $373.2\mu$: Y=72.45 $e^{0.04697x}$ shell height: 72.7 to $282.1\mu$: Y=54,96 $e^{0.04720x}$ shell breadth: 45.3 to $214.0\mu$ : Y=39.82 $e^{0.04927x}$ The relationships between the shell length and shell height and between the shell length and shell breadth are indicated as follows- shell height: 72.7 to $98.7\mu$ : Y=12.87780+0.63817X 108.4 to $206.4\mu$ : Y=0.90220+0.76456X 228.6 to $282.1\mu$ : Y=25.02630+0.69156X shell breadth: 45.3 to $77.8\mu$:Y=0.81373Xx-31.18914 87.4 to $157.7\mu$ : Y=13.37549+0.53230X 175.4 to $214.0\mu$: Y=30.24328+0.49545X

• Clinical and Experimental Reproductive Medicine
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• v.23 no.3
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• pp.247-268
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• 1996

It has been known for a long time that gonadotropins and steroid hormones play a pivotal role in a series of reproductive biological phenomena including the maturation of ovarian follicles and oocytes, ovulation and implantation, maintenance of pregnancy and fetal growth & development, parturition and mammary development and lactation. Recent investigations, however, have elucidated that in addition to these classic hormones, multiple growth factors also are involved in these phenomena. Most growth factors in reproductive organs mediate the actions of gonadotropins and steroid hormones or synergize with them in an autocrine/paracrine manner. The insulin-like growth factor(IGF) system, which is one of the most actively investigated areas lately in the reproductive organs, has been found to have important roles in a wide gamut of reproductive phenomena. In the present communication, published literature pertaining to the intrauterine IGF system will be reviewed preceded by general information of the IGF system. The IGF family comprises of IGF-I & IGF-II ligands, two types of IGF receptors and six classes of IGF-binding proteins(IGFBPs) that are known to date. IGF-I and IGF-II peptides, which are structurally homologous to proinsulin, possess the insulin-like activity including the stimulatory effect of glucose and amino acid transport. Besides, IGFs as mitogens stimulate cell division, and also play a role in cellular differentiation and functions in a variety of cell lines. IGFs are expressed mainly in the liver and messenchymal cells, and act on almost all types of tissues in an autocrine/paracrine as well as endocrine mode. There are two types of IGF receptors. Type I IGF receptors, which are tyrosine kinase receptors having high-affinity for IGF-I and IGF-II, mediate almost all the IGF actions that are described above. Type II IGF receptors or IGF-II/mannose-6-phosphate receptors have two distinct binding sites; the IGF-II binding site exhibits a high affinity only for IGF-II. The principal role of the type II IGF receptor is to destroy IGF-II by targeting the ligand to the lysosome. IGFs in biological fluids are mostly bound to IGFBP. IGFBPs, in general, are IGF storage/carrier proteins or modulators of IGF actions; however, as for distinct roles for individual IGFBPs, only limited information is available. IGFBPs inhibit IGF actions under most in vitro situations, seemingly because affinities of IGFBPs for IGFs are greater than those of IGF receptors. How IGF is released from IGFBP to reach IGF receptors is not known; however, various IGFBP protease activities that are present in blood and interstitial fluids are believed to play an important role in the process of IGF release from the IGFBP. According to latest reports, there is evidence that under certain in vitro circumstances, IGFBP-1, -3, -5 have their own biological activities independent of the IGF. This may add another dimension of complexity of the already complicated IGF system. Messenger ribonucleic acids and proteins of the IGF family members are expressed in the uterine tissue and conceptus of the primates, rodents and farm animals to play important roles in growth and development of the uterus and fetus. Expression of the uterine IGF system is regulated by gonadal hormones and local regulatory substances with temporal and spatial specificities. Locally expressed IGFs and IGFBPs act on the uterine tissue in an autocrine/paracrine manner, or are secreted into the uterine lumen to participate in conceptus growth and development. Conceptus also expresses the IGF system beginning from the peri-implantation period. When an IGF family member is expressed in the conceptus, however, is determined by the presence or absence of maternally inherited mRNAs, genetic programming of the conceptus itself and an interaction with the maternal tissue. The site of IGF action also follows temporal (physiological status) and spatial specificities. These facts that expression of the IGF system is temporally and spatially regulated support indirectly a hypothesis that IGFs play a role in conceptus growth and development. Uterine and conceptus-derived IGFs stimulate cell division and differentiation, glucose and amino acid transport, general protein synthesis and the biosynthesis of mammotropic hormones including placental lactogen and prolactin, and also play a role in steroidogenesis. The suggested role for IGFs in conceptus growth and development has been proven by the result of IGF-I, IGF-II or IGF receptor gene disruption(targeting) of murine embryos by the homologous recombination technique. Mice carrying a null mutation for IGF-I and/or IGF-II or type I IGF receptor undergo delayed prenatal and postnatal growth and development with 30-60% normal weights at birth. Moreover, mice lacking the type I IGF receptor or IGF-I plus IGF-II die soon after birth. Intrauterine IGFBPs generally are believed to sequester IGF ligands within the uterus or to play a role of negative regulators of IGF actions by inhibiting IGF binding to cognate receptors. However, when it is taken into account that IGFBP-1 is expressed and secreted in primate uteri in amounts assessedly far exceeding those of local IGFs and that IGFBP-1 is one of the major secretory proteins of the primate decidua, the possibility that this IGFBP may have its own biological activity independent of IGF cannot be excluded. Evidently, elucidating the exact role of each IGFBP is an essential step into understanding the whole IGF system. As such, further research in this area is awaited with a lot of anticipation and attention.