Biomedical subjects

B C Vanderhyden

Publications and source records attributed to B C Vanderhyden.

33 records · Page 2Linked to original sources

PubMed1993

Mouse oocytes regulate granulosa cell steroidogenesis.

Recent studies have demonstrated a critical role for the oocyte in proliferation and differentiation of granulosa cells and expansion of the cumulus oophorus in vitro. The purpose of this study was to determine if steroid production by cumulus granulosa cells was also modulated by oocytes. Mouse oocyte-cumulus cell complexes (intact) and complexes from which the oocytes were removed microsurgically (oocytectomized; OOX) were cultured for 24 h in the presence or absence of follicle-stimulating hormone (FSH; 150 ng/ml), testosterone (T; 5 x 10(-7) M) or both. Oocytectomy had no effect on the ability of cumulus cells to produce progesterone or estradiol in control cultures or in response to T. However, OOX complexes produced 17- and 36-fold more progesterone than intact complexes when cultured in the presence of FSH or FSH+T, respectively. Oocyte-conditioned medium (maximum 1 oocyte/2 microliters) had no effect on progesterone production by intact cumulus complexes, but reduced the progesterone production by OOX complexes by 75%. This inhibition was directly proportional to the number of oocytes used to condition the medium. Oocytectomy caused a slight decrease (29%) in estradiol production by complexes in the presence of FSH and T; however, OOX complexes in oocyte-conditioned medium produced almost twice as much estradiol as complexes in unconditioned medium. These results indicate that mouse oocytes secrete a factor(s) that inhibits progesterone and stimulates estradiol production by cumulus granulosa cells.

Animals↗

PubMed1993

The effect of cholecystokinin on intracellular Ca2+, membrane-associated protein kinase-C activity, and progesterone production in chicken granulosa cells.

Nerve fibers immunoreactive for cholecystokinin (CCK) have been observed in the rat ovary, but the function of this gut peptide in the ovary is not known. These studies were designed to investigate the effects of the CCK C-terminal octapeptide (CCK-8) on the intracellular calcium ion concentration ([Ca2+]i), protein kinase-C (PKC) activity, and progesterone secretion in granulosa cells obtained from the two largest preovulatory follicles (F1 and F2) of hens. [Ca2+]i was measured in cells loaded with the Ca(2+)-responsive fluorescent dye fura-2. The resting [Ca2+]i in these cells was 96 +/- 5 nM. There was a rapid (i.e. within 5-10 sec) 2- to 4-fold increase in [Ca2+]i in 70% of the cells examined after the addition of 10(-7) M CCK-8. The CCK-8-triggered [Ca2+]i transient was not affected by incubating the cells in Ca(2+)-free medium containing 2 mM EGTA or by pretreating the cells with a Ca2+ channel blocker, such as La3+ (1 mM) or D600 (100 microM). The CCK-8-triggered [Ca2+]i surge was abolished by pretreating the cells with the inhibitor of inositol phospholipid hydrolysis, neomycin (1.5 mM), the CCK antagonists proglumide (1 mM) and benzotript (1 mM), or pertussis toxin (50 ng/ml for 12 h). Incubating granulosa cells with CCK-8 (2 x 10(-7) M) for 10 min stimulated a 1.60 +/- 0.04-fold increase in membrane-associated PKC activity over control levels. In 3-h incubations, CCK-8 (10(-6)-10(-8) M) did not affect basal or LH (20 or 100 ng/ml-stimulated progesterone production. These studies demonstrate that CCK-8 causes a transient increase in chicken granulosa cell [Ca2+]i through the release of Ca2+ from intracellular stores and activates membrane-associated PKC activity, but does not affect progesterone production. These results suggest the presence of G-protein-coupled phospholipase-C-activating CCK receptors on the surface of these cells.

Animals↗

PubMed1993

Species differences in the regulation of cumulus expansion by an oocyte-secreted factor(s).

The expansion of the mouse cumulus oophorus in vitro in response to FSH is dependent upon the presence of an enabling factor secreted by the oocyte. The purpose of this study was to determine whether the expansion of cumulus cells from rats and pigs were similarly dependent upon an oocyte-secreted enabling factor. Mouse and rat oocyte-cumulus cell complexes were isolated from pregnant mares' serum gonadotrophin (PMSG)-stimulated animals; pig oocyte-cumulus cell complexes with the attached piece of mural granulosa were obtained from either prepubertal gilts or cyclic sows. FSH (25-1000 ng ml-1) or dibutyryl cyclic adenosine monophosphate (dbcAMP; 0.05-2 mmol l-1) induced a dose-dependent expansion of the oocyte-cumulus complexes from rats and pigs. The hypothesis that the oocyte plays a role in the regulation of cumulus expansion was tested by microsurgically removing oocytes from oocyte-cumulus complexes and the oocytectomized complexes were tested for their ability to undergo expansion in response to FSH. FSH did not induce cumulus expansion in oocytectomized mouse complexes; however, expansion occurred in rat and pig oocytectomized complexes. The pieces of mural granulosa, detached from the pig complexes, also expanded in response to FSH stimulation. Rat and pig oocytectomized complexes were then held in culture for up to 48 h before stimulation by FSH. The degree of expansion in rat oocytectomized complexes decreased as the delay before FSH stimulation increased such that, with an 8 h delay, oocytectomized complexes did not expand.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Mouse oocytes promote proliferation of granulosa cells from preantral and antral follicles in vitro.

Evidence is now emerging that the oocyte plays a role in the development and function of granulosa cells. This study focuses on the role of the oocyte in the proliferation of (1) undifferentiated granulosa cells from preantral follicles and (2) more differentiated mural granulosa cells and cumulus granulosa cells from antral follicles. Preantral follicles were isolated from 12-day-old mice, and mural granulosa cells and oocyte-cumulus complexes were obtained from gonadotropin-primed 22-day-old mice. Cell proliferation was quantified by autoradiographic determination of the 3H-thymidine labeling index. To determine the role of the oocyte in granulosa cell proliferation, oocyte-cumulus cell complexes and preantral follicles were oocytectomized (OOX), oocytectomy being a microsurgical procedure that removes the oocyte while retaining the three-dimensional structure of the complex or follicle. Mural granulosa cells as well as intact and OOX complexes and follicles were cultured with or without FSH in unconditioned medium or oocyte-conditioned medium (1 oocyte/microliter of medium). Preantral follicles were cultured for 4 days, after which 3H-thymidine was added to each group for a further 24 h. Mural granulosa cells were cultured as monolayers for an equilibration period of 24 h and then treated for a 48-h period, with 3H-thymidine added for the last 24 h. Oocyte-cumulus cell complexes were incubated for 4 h and then 3H-thymidine was added to each group for an additional 3-h period. FSH and/or oocyte-conditioned medium caused an increase in the labeling index of mural granulosa cells in monolayer culture; however, no differences were found among treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

A new, nongenomic estrogen action: the rapid release of intracellular calcium.

We have investigated the effects of steroids on the intracellular calcium ion concentration [Ca2+]i in chicken granulosa cells obtained from the two largest preovulatory follicles of laying hens. [Ca2+]i was measured in cells loaded with the Ca(2+)-responsive fluorescent dye fura-2. The resting [Ca2+]i in these cells was 100 +/- 5 nM. There was an immediate (i.e. less than 5 sec) 4- to 8-fold increase in [Ca2+]i in all of the 76 cells examined after the addition of 10(-7) M estradiol-17 bdta. Estradiol-17 beta was effective between 10(-10)-10(-6) M. Estradiol-17 alpha, estrone, and estriol (10(-8)-10(-6) M) were as effective as estradiol-17 beta, but the progestins, pregnenolone, and progesterone, and the androgens, testosterone, androstenedione, or 5 alpha-dihydrotestosterone were ineffective at concentrations up to 10(-5) M. The prompt estradiol-17 beta-induced [Ca2+]i spike was not affected by incubating the cells in Ca(2+)-free medium containing 2 mM EGTA or by pretreating them with the Ca2+ channel blockers lanthanum (1 mM), cobalt (5 mM), methoxyverapamil (D600; 50 microM), or nifedipine (20 microM). The estrogen-triggered [Ca2+]i surge was also not affected by pretreating the cells with the conventional estrogen receptor antagonist tamoxifen (10(-5) M), or the RNA and protein synthesis inhibitors actinomycin D (1 microgram/ml) and cycloheximide (1 microgram/ml), but was abolished by pretreating the cells with inhibitors of inositol phospholipid hydrolysis, neomycin (1.5 mM) and U-73,122 (2.5 microM). The closely related, but inactive, compound U-73,343 (1 microM) did not affect the estrogen-triggered [Ca2+]i surge. Estradiol-17 beta (10(-7) M), but not progesterone (10(-5) M), also triggered a large [Ca2+]i surge in pig granulosa cells, which, like the [Ca2+]i surge in chicken granulosa cells, was almost immediate, transient, and unaffected by incubation in Ca(2+)-free medium or pretreatment with methoxyverapamil (D600; 50 microM), lanthanum (1 mM), or tamoxifen (10(-5)M). However, granulosa cells from immature rats primed with diethylstilbestrol or PMSG did not respond to estradiol-17 beta, even at concentrations as high as 10(-5) M, although they promptly generated a [Ca2+]i transient upon exposure to LHRH (10(-5) M). These results suggest that estrogens almost instantaneously trigger the release of Ca2+ from intracellular stores which may be mediated through phosphoinositide breakdown. The striking rapidity of this estrogen-induced internal Ca2+ mobilization is consistent with the activation of a cell surface receptor which is different from the conventional slowly acting, gene-stimulating nuclear estrogen receptor.

Androgens↗

PubMed1991

Hormonal actions during oocyte maturation influence fertilization and early embryonic development.

On the basis of evidence just reviewed, the hormonal requirements during IVM of mammalian oocytes for fertilization and developmental competence may be summarized as follows: 1. Nuclear maturation occurs "spontaneously," without follicular factors or hormones, in all mammalian species. 2. Cumulus cells are necessary during nuclear maturation in culture for fertilization and developmental competence. Their effect is enhanced by the addition of serum or follicular fluid to the maturation medium. 3. FSH retards nuclear maturation, perhaps thereby enhancing subsequent developmental competence by allowing more time for cytoplasmic maturation to occur before fertilization. The effects of FSH are mediated, in part, by soluble factors from cumulus or granulosa cells. 4. FSH in vivo before culture or added in vitro to IVM culture media enhances fertilization and stimulates steroidogenesis (progesterone and estradiol) in cumulus cells. Blockade of steroidogenesis prevents the enhancing effect of FSH on fertilization. Progesterone can substitute for FSH in enhancing fertilization of rat oocytes. 5. Other hormones enhance beneficial effects of FSH, with some apparent species differences: a. Rat: Progesterone may mediate the FSH effect. b. Cow, rabbit: Estradiol enhances the beneficial effect of FSH. c. Rabbit: Prolactin further enhances the effects of estradiol and FSH. d. Human: No evidence is available on the possible synergism between steroids and gonadotropins in enhancing in vitro maturation. It is clear that further research is required to elucidate the mechanisms of action of all the hormones that have been observed to influence oocyte maturation, and to establish the physiologic significance of most of these, particularly in species other than laboratory rodents. Major benefits to animal production and human health are likely to accrue from such research.

Animals↗

PubMed1990

Effects of gonadotropins and granulosa cell secretions on the maturation and fertilization of rat oocytes in vitro.

Fully grown germinal vesicle-stage oocytes are induced to resume meiosis and acquire the capacity to undergo fertilization in response to a surge of gonadotropins. The present study examined possible direct and indirect roles of gonadotropins in the maturation and fertilization of rat oocytes by determining 1) the effect of exogenous administration of gonadotropins (priming) to immature rats prior to oocyte collection on the capacity of oocytes to undergo maturation and fertilization in vitro, 2) the effect of follicle-stimulating hormone (FSH) in the maturation media on the resumption of meiosis and subsequent capacity of oocytes to undergo fertilization, and 3) the capacity of oocytes to undergo maturation and fertilization following culture in preovulatory follicular fluid or in conditioned media obtained from gonadotropin-stimulated granulosa cell (GC) cultures. In the first experiment, oocytes from unprimed rats underwent spontaneous meiotic maturation in vitro and 17% underwent subsequent fertilization. Priming increased the proportion of oocytes undergoing fertilization. Maturation of oocytes in media supplemented with various concentrations of FSH or for various lengths of time (6-16 h) in medium with 500 ng FSH/ml indicated that FSH slowed the rate of meiotic maturation, but had no effect on the capacity of the oocytes to be fertilized. Oocytes obtained from primed animals and cultured in the presence of preovulatory follicular fluid were fertilized in proportions similar to those cultured in serum-containing medium. In the third experiment, medium conditioned by FSH-stimulated GC for 40 h slowed the rate of meiotic maturation; the addition of luteinizing hormone (LH) to the FSH-stimulated cells produced a medium in which the rate of oocyte maturation was not different from that of control oocytes (in medium from unstimulated cells). Medium conditioned by FSH- or LH-stimulated GC, but not fibroblasts, increased the proportions of oocytes undergoing fertilization following maturation in those media. FSH + LH stimulation of GC increased the fertilization of oocytes to proportions significantly higher than with either gonadotropin alone. These data suggest that GC respond to gonadotropin stimulation by providing a factor(s) that regulates the rate of oocyte maturation and promotes the capacity of oocytes to undergo fertilization.

Animals↗

PubMed1990

Developmental pattern of the secretion of cumulus expansion-enabling factor by mouse oocytes and the role of oocytes in promoting granulosa cell differentiation.

The expansion, or mucification, of the mouse cumulus oophorus in vitro requires the presence of an enabling factor secreted by the oocyte as well as stimulation with follicle-stimulating hormone (FSH). This study focuses on (1) the ability of mouse oocytes to secrete the enabling factor at various times during oocyte growth and maturation, (2) the temporal relationships between the development of the capacity of the oocyte to undergo germinal vesicle breakdown, the ability of the oocyte to secrete cumulus expansion-enabling factor, and the capacity of the cumulus oophorus to undergo expansion, and (3) the role of the oocyte in the differentiation of granulosa cells as functional cumulus cells. Growing, meiotically incompetent oocytes did not produce detectable amounts of cumulus expansion-enabling factor, but fully grown meiosis-arrested oocytes, maturing oocytes, and metaphase II oocytes did. Detectable quantities of enabling factor were produced by zygotes, but not by two-cell stage to morula embryos. The ability of oocytes to secrete cumulus expansion enabling factor and the capacity of cumulus cells to respond to FSH and the enabling factor are temporally correlated with the acquisition of oocyte competence to undergo germinal vesicle breakdown. Mural granulosa cells of antral follicles do not expand in response to FSH even in the presence of cumulus expansion-enabling factor, showing that mural granulosa cells and cumulus cells are functionally distinct cell types. The perioocytic granulosa cells of preantral follicles isolated from 12-day-old mice differentiate into functional cumulus cells during a 7-day period in culture. Oocytectomized granulosa cell complexes grown in medium conditioned by either growing or fully grown oocytes were comparable in size to intact complexes and maintained their 3-dimensional integrity to a greater degree than oocytectomized complexes grown in unconditioned medium. After 7 days, the oocytectomized complexes were stimulated with FSH in the presence of enabling factor, but no expansion was observed whether or not the oocytectomized complexes grew in the presence of oocyte-conditioned medium. These results suggest that a factor(s) secreted by the oocyte affects granulosa cell proliferation and the structural organization of the follicle, but continual close association with the oocyte appears necessary for the differentiation of granulosa cells into functional cumulus cells, insofar as they are capable of undergoing expansion.

Animals↗

PubMed1990

FSH-induced expansion of the mouse cumulus oophorus in vitro is dependent upon a specific factor(s) secreted by the oocyte.

Although it has been shown that granulosa cells regulate the growth and meiotic maturation of mammalian oocytes, there is little evidence of a role for the oocyte in the differentiation or function of granulosa cells. To test the hypothesis that the oocyte participates in the regulation of granulosa cell function, oocytes were removed from isolated oocyte-cumulus cell complexes by a microsurgical procedure and oocytectomized complexes were tested for their ability to undergo expansion in response to follicle-stimulating hormone (FSH). FSH increased the levels of intracellular cAMP, the activity of the hyaluronic acid-synthesizing enzyme system, and induced cumulus expansion in intact complexes. In contrast, FSH did not induce increased hyaluronic acid-synthesizing enzyme activity or cumulus expansion in oocytectomized complexes. Therefore, the participation of the oocyte is necessary for the cumulus cells to synthesize hyaluronic acid and undergo cumulus expansion in vitro in response to stimulation with FSH. FSH induced the elevation of intracellular cAMP to the same extent in both intact and oocytectomized complexes and the cAMP analog 8-bromo cyclic adenosine monophosphate (8Br-cAMP) did not stimulate expansion in oocytectomized complexes. Therefore, the influence of the oocyte on cumulus expansion occurs downstream from the elevation of cAMP levels in the cumulus cells. Epidermal growth factor (EGF), a potent stimulator of cumulus expansion in intact complexes, which probably acts by a mechanism at least initially different from FSH, failed to stimulate cumulus expansion after oocytectomy. Next, oocytectomized complexes were either cocultured with germinal vesicle stage denuded oocytes or cultured in medium conditioned by denuded oocytes. In both cases, FSH or EGF stimulated expansion by oocytectomized complexes. The degree of expansion was directly correlated to the number of oocytes used to condition the medium. Contact between the oocyte and the cumulus cells is not necessary for cumulus expansion. Rather, a factor(s) secreted by the oocyte is necessary for the cumulus cells to undergo expansion in response to either FSH or EGF. FSH did not induce expansion of oocytectomized complexes in media conditioned by various somatic cells such as granulosa cells, fibroblasts, and Sertoli cells; by a mixed population of male germ cells; or by spermatozoa. This suggests that the expansion enabling activity is specific to the oocyte. These results demonstrate that the oocyte participates in the regulation of cumulus cell function.

Cells, Cultured↗

PubMed1989

Role of cumulus cells and serum on the in vitro maturation, fertilization, and subsequent development of rat oocytes.

Immature oocytes were collected from immature female rats (60-65 g) 40 h after injection with 6 IU pregnant mare's serum gonadotropin (PMSG). Oocytes were matured cumulus-intact (CI) or cumulus-free (CF) in medium supplemented with 0.5% bovine serum albumin (BSA) or 5-20% serum for periods of up to 24 h. After assessment for nuclear maturation, the oocytes were exposed to epididymal sperm for fertilization in vitro. In vitro-matured and ovulated oocytes undergoing fertilization were transferred to unilaterally pregnant recipients for embryonic and fetal development. The presence of cumulus cells and serum shortened (by 2 h) the time required for polar body emission by in vitro-matured oocytes and also helped to increase significantly the penetrability of the oocytes by spermatozoa. A high proportion (45.6%) of fertilized oocytes showed evidence of abnormal fertilization following maturation in the absence of cumulus cells. Oocytes matured CI before fertilization were able to develop to viable fetuses (57.8%) in proportions similar to ovulated oocytes (55.0%) after in vitro fertilization. These findings indicate an essential role for cumulus cells in promoting normal cytoplasmic maturation of oocytes necessary for pronuclear formation and subsequent developmental capability.

Animals↗

PubMed1989

Zona drilling increases the penetrability of rat oocytes matured in vitro.

Immature rat follicular oocytes were cultured either with cumulus cells intact (CI) or cumulus-free (CF) in bovine serum albumin (BSA)- or serum-supplemented medium under conditions in which meiotic maturation occurs spontaneously. After 12 h of culture to permit in vitro maturation (IVM), the cumulus cells were stripped from the CI group. Control oocytes recovered 2-4 h after ovulation from oviducts of pregnant mare's serum gonadotropin (PMSG)-treated rats were similarly stripped of cumulus cells. Half the oocytes in each group had holes "drilled" in their zonae pellucidae by topical application of acid Tyrode's solution with a micropipette to enable bypass of the zona barrier to penetration. They were cultured for a further 14-16 h with epididymal sperm and then were assessed for sperm penetration and pronuclear formation. In a preliminary study using various concentration of sperm, 50,000 sperm/ml was identified as an appropriate concentration and was used in all subsequent experiments. For oocytes matured in serum-supplemented medium, penetration rates of non-drilled oocytes-expressed as a percentage of oocytes exposed to sperm for CF, CI, and ovulated oocytes were 10%, 34%, and 80%, respectively (p less than 0.01). Drilling significantly increased the penetration rates of both IVM groups (CF: 40%, CI: 77%) but not of ovulated oocytes (78%). Forty-one percent of non-drilled CF oocytes failed to form normal pronuclei after penetration. This was significantly higher than either the CI (0%) or ovulated (1%) groups (p less than 0.001). Drilling increased the incidence of failure to form normal pronuclei in penetrated oocytes of the CF group (64%) but not of the CI or ovulated groups.2z=

Animals↗

PubMed1988

Decreased embryonic survival of in-vitro fertilized oocytes in rats is due to retardation of preimplantation development.

Immature female rats (60-65 g) were injected with 4 i.u. PMSG on Day -2 and allocated to 3 groups. On the evening of Day 0, rats in Groups I and II were allowed to mate. Embryos were collected on Day 4 (Group I, control morulae) or Day 5 (Group II, control blastocysts) and were transferred into the oviduct or uterine horn of Day-4 pregnant recipient rats. On the transfer side of the recipients, the bursa had been peeled from around the ovary to prevent endogenous oocytes from entering the oviduct. For Group III, unmated donors were killed 65-67 h after PMSG injection. Ovulated oocytes recovered from the oviducts were fertilized in vitro and transferred 16-18 h later. Embryos developing from in-vitro fertilized (IVF) oocytes were recovered on Day 5, separated into morulae (Group IIIm) and blastocysts (Group IIIb) and transferred into Day-4 pregnant recipients similar to control embryos. Some embryos from each group were used to determine the mean number of cells/embryo. Embryo recipients were killed on Day 20. After transfer, the development of IVF oocytes was retarded compared to control embryos. IVF morulae contained significantly fewer cells/embryo than did control morulae but were able to implant and grow to fetuses, in proportions similar to controls, if transferred into the oviduct of the recipients. These results suggest that the developmental potential of rat oocytes fertilized in vitro is limited due to asynchrony between the embryo and the uterine environment at the time of implantation, rather than possible defects incurred by the oocyte during the fertilization procedure.

Animals↗

PubMed1986

Effect of removal of the ovarian bursa of the rat on infundibular retrieval and subsequent development of ovulated oocytes.

The ovarian bursa was peeled from around one ovary of each rat and the rats were killed 1, 2, 3, 4 and 5 weeks later. The proportion of rats that maintained a bursa-free ovary did not change over the 5-week period (80-89%). Ovulation from the peeled ovary occurred in all rats but oocytes (1-4) were found in the ipsilateral oviduct in only 18% of the rats. The presence of oocytes in the oviduct was normally associated with some degree of re-encapsulation of the ovary. In another experiment rats were mated within 1 week of removal of the bursa from around the ovary. Unilateral pregnancy resulted in 92% of the rats. In a third experiment fertilized oocytes from mated donor rats were transferred into the oviduct next to the peeled ovary in 15 mated recipients. Of 85 zygotes transferred, 51 survived to be viable fetuses on Day 20. A single fetus developing from an endogenous oocyte was found in the transfer uterine horn in only one rat. This preparation may be useful in studies which attempt to determine the viability of oocytes that have undergone various manipulations in vivo or in vitro.

Animals↗

PubMed1986

Increased mortality during early embryonic development after in-vitro fertilization of rat oocytes.

Immature female rats (60-65 g) were injected with 4 i.u. PMSG on Day -2, and allocated to 3 groups. For Groups I and II, unmated donors were killed 67-69 h after PMSG injection, shortly after the expected time of ovulation. Oocytes were recovered from the oviducts and transferred immediately into the oviduct of mated recipients (Group I) whose ipsilateral ovary had been exposed by peeling back the bursa, preventing endogenous oocytes from entering the oviduct, or were fertilized in vitro (Group II) and were transferred 16-18 h later. Rats in Group III were allowed to mate and half were killed 6 h after mating. The fertilized oocytes were then incubated for 10-12 h until transfer. The remaining rats in Group III were killed 16-18 h after mating and fertilized oocytes were collected and transferred immediately. Recipient rats were killed on Days 2, 5, 8 and 20. Zygotes resulting from in-vitro fertilization (Group II) were as able as those fertilized in donors (Group III) or recipients (Group I) to develop to the 2-cell stage, but underwent significantly greater embryonic loss beyond this stage of development. There was a slower rate of development of such oocytes to the blastocyst stage (Day 5) and a lower mean weight of implantation sites (Day 8). Transfer of zygotes after in-vitro fertilization resulted in a loss of 35% of the embryos at the time of implantation. These results suggest that in-vitro fertilization of rat oocytes leads to defects in the embryos causing a delay in early embryo development and a large number of implantation losses.

Animals↗

PubMedDate not supplied

Translational research in ovarian cancer: a must.

Ovarian cancer discovered at late clinical stage continues to be a fatal disease. It seems self-evident that if we are to make an impact on the survival of advanced ovarian cancer patients, we must begin to understand the disease more completely. This should improve the diagnosis of the disease at an early stage when it is curable by surgery or develop better/targeted drug treatments. Modern molecular techniques have provided insights into many of the molecular changes that occur when ovarian cancer develops, but one must understand that changes seen in this way can only be said to correlate with disease. It would be helpful to have a way to test candidate changes for causality. In many cancer types, genetically engineered animals are beginning to be used for this purpose and as a means to study the disease process in greater detail. To date, there has been no way to study ovarian cancer by this means. Efforts to model human ovarian cancer have been delayed by a general lack of understanding both of the disease process in humans and of the cells widely believed to be the precursors of epithelial ovarian cancer, the ovarian surface epithelial (OSE) cells. Here, we present recent progress in modeling ovarian cancer using genetically modified mice.

Animals↗