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R G Gosden

Publications and source records attributed to R G Gosden.

At least 73 records · Page 4Linked to original sources
PubMed1992

Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause.

Menopause is triggered by the number of ovarian follicles falling below a threshold number and is irreversible because oogonial stem cells disappear after birth. Since it is the result of programmed disappearance of a limited store of follicles, menopause can be predicted using mathematical models based on total follicle counts at different ages. Our model shows follicle numbers decline bi-exponentially rather than as a simple exponential function of age, as had been assumed, with a first exponential rate parameter of -0.097 and a second of -0.237. The change occurred when numbers had fallen to the critical figure of 25,000 at age 37.5 years. The unexpectedly faster rate of ovarian ageing afterwards lowers the follicle population to 1000 at approximately 51 years, and was adopted as the menopausal threshold because it corresponds to the median age of menopause in the general population. Had the earlier rate persisted menopause would not be expected until 71 years. The impact of step reductions of follicle numbers on the prospective span of menstrual life was predicted by the model. A reduction by 50% before age 30 years resulted in the threshold being reached at 44 years and 0.6 year later for every subsequent year until age 37.5 years after which it is reached at 48 years. A reduction of 90% in childhood before age 14 years could result in menopause as early as 27 years, with increments of 0.6 year per year afterwards until after 37.5 years when it is expected at age 41 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

An investigation by mathematical modelling of whether mouse and human preimplantation embryos in static culture can satisfy their demands for oxygen by diffusion.

Mammalian preimplantation embryos are conventionally grown in small, static droplets of medium. By contrast, embryos within the oviduct are subject to mixing forces arising from the action of cilia and the contractions of the myosalpinx. Such forces will minimize the buildup of unstirred layers around the embryos and facilitate the exchange of gases and metabolites. We have devised a mathematical model to investigate whether preimplantation mouse and human embryos grown in static culture can satisfy their requirement for oxygen solely by diffusion i.e. in the absence of stirring. The model incorporates the diffusion coefficients for oxygen in the medium outside and within the embryo, the oxygen tension of the culture medium, the size of the embryo and its oxygen uptake. Solutions of the model are provided for mouse oocytes and 2-cell embryos, mouse blastocysts and human morulae. In each case, the model is solved for two different values of the diffusion coefficient of oxygen within the cell and of the oxygen content of the medium (5 and 20%). The conclusion is that mouse embryos in static culture are likely to be able to satisfy their demands for oxygen by diffusion alone, but that human embryos may become marginally hypoxic, especially at lower oxygen levels.

Animals↗
PubMed1991

Sex chimaerism, fertility and sex determination in the mouse.

Adult intraspecific mouse chimaeras, derived by introducing male embryonal stem cells into unsexed host blastocysts, were examined to determine whether gonadal sex was correlated with the sex chromosome composition of particular cell lineages. The fertility of XX in equilibrium XY and XY in equilibrium XY male chimaeras was also compared. The distribution of XX and XY cells in 34 XX in equilibrium XY ovaries, testes and ovotestes was determined by in situ hybridisation using a Y-chromosome-specific probe. Both XX and XY cells were found in all gonadal somatic tissues but Sertoli cells were predominantly XY and granulosa cells predominantly XX. The sex chromosome composition of the tunica albuginea and testicular surface epithelium could not, in general, be fully resolved, owing to diminished hybridisation efficiency in these tissues, but the ovarian surface epithelium (which like the testicular surface epithelium derives from the coelomic epithelium) was predominantly XX. These findings show that the claim that Sertoli cells were exclusively XY, on which some previous models of gonadal sex determination were based, was incorrect, and indicate instead that in the mechanism of Sertoli cell determination there is a step in which XX cells can be recruited. However, it remains to be established whether the sex chromosome constitution of the coelomic epithelium lineage plays a causal role in gonadal sex determination. Male chimaeras with XX in equilibrium XY testes were either sterile or less fertile than chimaeras with testes composed entirely of XY cells. This impaired fertility was associated with the loss of XY germ cells in atrophic seminiferous tubules. Since this progressive lesion was correlated with a high proportion of XX Leydig cells, we suggest that XX Leydig cells are functionally defective, and unable to support spermatogenesis.

Animals↗
PubMed1991

Impact of exogenous progesterone on ovarian follicular dynamics and function in mice.

Raising progesterone concentrations in young adult mice by subcutaneous implants resulted in ovulation being blocked and the cessation of oestrous cycles. The effect of this treatment on the numbers and dynamics of preantral follicles during 36 days of treatment was studied using a compartmental model to analyse differential follicle counts. Changes in growth and/or death rates were detected at all stages of follicular development. An increased rate of growth through preantral stages was predicted in the treatment group when compared with the controls, but most of these follicles did not reach the antral stage of development as an increased death rate was observed at large preantral stages (stage IV). Antral follicles were formed in the treatment group, but all succumbed to atresia. Increased atresia in the antral population of follicles in the treatment group was observed directly.

Animals↗
PubMed1990

Characterization of ovarian follicular fluids of sheep, pigs and cows using proton nuclear magnetic resonance spectroscopy.

Proton NMR spectra were produced for Graafian follicular fluids obtained by aspiration from sheep, pig and cow ovaries. The following low molecular mass, non-protein-bound metabolites were detected at concentrations exceeding 0.1 mM: acetate, alanine, creatinine/creatine, glycine, D-3-hydroxybutyrate, lactate, valine. Glucose was difficult to quantify and N-acetyl sugars gave a broad resonance at 2.06 ppm, presumably representing side-chains of glycoproteins. Ethanol was detected at up to millimolar concentrations in some specimens, though the physiological significance of this finding was not clear. The concentrations of all metabolites were comparable to those of plasma. These results have therefore shown that NMR spectroscopy is useful for gaining a broad and semiquantitative impression of the more abundant metabolites in the fluids of preovulatory Graafian follicles.

3-Hydroxybutyric Acid↗
PubMed1990

Restitution of fertility in sterilized mice by transferring primordial ovarian follicles.

Primordial follicles isolated from infant mouse ovaries by enzymatic disaggregation have been transferred to the ovaries of sterile adults. They were transferred after being recombined and incubated in a plasma clot which was inserted either into ovaries which had been sterilized by X-irradiation or into vacant periovarian capsules immediately after ovariectomy. Irrespective of the type of operation, these grafts underwent morphogenesis to form replicas of the normal ovary, which were generally indistinguishable in respect of form, histological appearance and function. The numbers of follicles in these so-called transgerminative ovaries were highly variable, but all stages of follicular maturation up to Graafian stage were represented in most of them, while grafts that had been X-irradiated before transfer were sterile. Ovaries forming from fertile grafts were capable of spontaneous ovulation and the majority of animals carrying them were sexually receptive to males. Mating often resulted in pregnancies and those delivering at full-term produced normal offspring.

Animals↗
PubMed1990

Restitution of fertility in sterilized mice by transferring primordial ovarian follicles.

Primordial follicles isolated from infant mouse ovaries by enzymatic disaggregation have been transferred to the ovaries of sterile adults. They were transferred after being recombined and incubated in a plasma clot which was inserted either into ovaries which had been sterilized by X-irradiation or into vacant periovarian capsules immediately after ovariectomy. Irrespective of the type of operation, these grafts underwent morphogenesis to form replicas of the normal ovary, which were generally indistinguishable in respect of form, histological appearance and function. The numbers of follicles in these so-called transgerminative ovaries were highly variable, but all stages of follicular maturation up to Graafian stage were represented in most of them, while grafts that had been X-irradiated before transfer were sterile. Ovaries forming from fertile grafts were capable of spontaneous ovulation and the majority of animals carrying them were sexually receptive to males. Mating often resulted in pregnancies and those delivering at full-term produced normal offspring.

Animals↗
PubMed1990

Morphological study of cultured preantral ovarian follicles of mice after transplantation under the kidney capsule.

Isolated ovarian follicles taken from 10-day-old mice and cultured in collagen gel for 5 days, in the presence or absence of serum, were transplanted under the kidney capsule of ovariectomized mice. Hosts showed vaginal opening within 5 days and cornified vaginal smears by 9 days. Follicles proceeded to Graafian stages and luteinization occurred. Ovulation was not observed and oocytes degenerated within the luteinized follicle. Theca formation was preceded by the appearance of blood vessels within the graft. In-vitro fertilisation of harvested oocytes resulted in embryos.

Animals↗
PubMed1990

Extra-ovarian production of mature viable mouse oocytes from frozen primary follicles.

Isolated primary mouse follicles can be frozen successfully and thawed in the presence of 1.5 m-DMSO. Similar proportions of freshly collected and frozen-thawed primary follicles undergo folliculogenesis in the absence of other ovarian tissue. Some of the mature oocytes recovered from these follicles were fertilized in vitro and, after transfer to pseudopregnant recipients at the 2-cell stage, developed into live young. Cryopreservation and extra-ovarian development of immature follicles provide a unique opportunity to store large numbers of female gametes.

Animals↗
PubMed1989

Ultrastructural and histochemical investigations of Call-Exner bodies in rabbit Graafian follicles.

In a histological survey of 19 mammalian species, Call-Exner bodies of conventional size and appearance were found in only 5, namely, human, rhesus monkey, rabbit, guinea-pig and sheep. Rabbit ovaries were used for characterizing these bodies using quantitative histochemistry, lectin binding and electron microscopy. Call-Exner bodies were topographically distinct lacunae of the extracellular space probably containing hyaluronic acid with proteoglycan complexes. The staining characteristics of the antrum and Call-Exner bodies were generally similar. However, in contrast to the antrum, the smaller lacunae contained suspended filaments with a distinctive peripheral membrane upon which a rosette of granulosa cells was resting. The membrane and narrow intercellular clefts probably prevent much exchange of large glycosaminoglycan complexes with the antrum. The origin and significance of Call-Exner bodies require further study, but it is clear that they are associated with secretion rather than with necrosis as sometimes suggested.

Animals↗
PubMed1989

Ovarian cyclicity and follicular recruitment in unilaterally ovariectomized mice.

Halving the numbers of follicles in young adult mice by unilateral ovariectomy resulted in compensatory Graafian follicle growth with a reduction by about 25% of the expected number of oestrous cycles. The impact of the operation on the numbers and dynamics of preantral follicles during the first 2 months after ovariectomy was studied using a compartmental mathematical model to analyse differential follicle counts. There were changes in growth and/or death rates at all stages of follicle development, and the patterns emerging were time-dependent. The rate of follicle survival from the pool of unilaminar stages was paradoxically reduced, but those forming two granulosa cell layers continued to develop towards Graafian size. As the frequency of follicle death declined, the numbers of healthy large preantral and antral stages in unpaired ovaries rose to approach those in pairs of age-matched control ovaries, suggesting that follicles otherwise undergoing atresia were being rescued. In the long-term, follicle dynamics after unilateral ovariectomy at young ages did not appear to compromise fecundity seriously.

Animals↗
PubMed1989

Quantitative study of the development of isolated mouse pre-antral follicles in collagen gel culture.

Follicles were isolated from the ovaries of 10-day-old C57BL6/CBA F1 hybrids by mechanical and enzymic treatment, embedded in a collagen-gel matrix to maintain the 3 dimensional integrity of the follicle and cultured for up to 14 days. Gels were removed at various times during the culture period and prepared for histology. Follicles grew from unilaminar to multilaminar stages within 6 days of the culture period. A more detailed assessment of growth by counting follicles at different stages and measuring oocyte and follicle diameters showed that follicle growth was maintained for up to 14 days in culture. Initially the proportion of unhealthy follicles was high but this declined after 6 days in culture.

Animals↗
PubMed1989

Interruption of parturition in rats by morphine: a result of inhibition of oxytocin secretion.

Oxytocin secretion is inhibited by opioids, and oxytocin is important in parturition. The effects on parturition of morphine, a relatively selective mu-opioid receptor agonist, were studied in the rat. Morphine or vehicle with or without the opiate antagonist naloxone were administered immediately after the birth of the second pup and the subsequent course of parturition was recorded in a total of 80 rats. Both s.c. morphine (10 mg/kg) and intracerebroventricular (i.c.v.) morphine (18 micrograms through a previously implanted cannula) interrupted parturition, delaying the birth of the sixth pup after treatment to 187.3 +/- 35.9 (S.E.M.) min and 195.4 +/- 19.5 min respectively, compared with 46.4 +/- 3.7 and 66.1 +/- 17.5 min after vehicle alone. The dose of morphine given i.c.v. had no effect when given s.c. Naloxone given concurrently prevented the effects of morphine. Eventually the rate of parturition in the morphine-treated groups recovered. Perinatal pup mortality rate was not increased when morphine was given to the mothers, but it did inhibit the expression of normal intrapartum maternal behaviour. Pup mortality was increased 48 h post partum by morphine given during parturition, and it reduced the proportion of rats with normal maternal behaviour 24 h post partum. Morphine did not affect spontaneous or oxytocin-stimulated contractile activity of the parturient uterus in vitro. The concentration of oxytocin in trunk blood plasma was decreased 40 min after i.c.v. morphine (24.3 +/- 3.9 vs 39.3 +/- 6.5 pmol/l in controls), as was vasopressin (7.2 +/- 1.5 vs 19.7 +/- 4.5 pmol/l in controls). Intravenous infusion of oxytocin (2-5 mU/min for 144.3 +/- 8.2 min; total infused 448.5 +/- 61.9 mU) after i.c.v. morphine re-started parturition; all pups were born to these rats (mean time to pup 6, 110.3 +/- 12.7 min) before the i.v. vehicle-infused rats given i.c.v. morphine re-started (mean time to pup 6, 406.3 +/- 125.2 min). It is concluded that morphine given during parturition acts centrally through opioid receptors to inhibit oxytocin secretion, and impairs the expression of maternal behaviour. Reversal of the effects of morphine on parturition by i.v. oxytocin demonstrates the important role of oxytocin in fetus ejection and expulsion.

Animals↗
PubMed1988

Electrophysiological properties of the follicle wall in the pig ovary.

The transmural potential difference and short-circuit current of the porcine Graafian follicle have been measured in an attempt to test whether antral fluid accumulates as a result of active transport of salt. The values obtained by mounting explants of follicle wall in Ussing chambers were close to zero and the specific electrical resistance was only 59 delta.cm2. The elemental composition of the follicular fluid was similar to that of ovarian venous plasma with the exception of follicular Na+ which was slightly more abundant. Bicarbonate concentrations were slightly lower in follicular fluids. These findings were interpreted as evidence that the follicular wall is a leaky epithelium and, therefore, any charge resulting from net ion transport will be shunted along low resistance paracellular pathways.

Animals↗
PubMed1988

The CBA mouse as a model for age-related aneuploidy in man: studies of oocyte maturation, spindle formation and chromosome alignment during meiosis.

To elucidate the possible mechanism of disturbances in chromosome segregation leading to the increase in aneuploidy in oocytes of aged females we examined the meiotic spindles of CBA/Ca mice. Employing immunofluorescence with an anti-tubulin antibody, and human scleroderma serum, as well as 4'-6-diamidino-2-phenylindole (DAPI) staining of chromosomes the microtubular cytoskeleton could be visualized, and the behaviour of chromosomes and centromeres of oocytes spontaneously maturing in vitro could be studied. The morphology of spindles during the first meiotic division was not conspicuously different in oocytes from young and aged mice as far as the cytoskeletal elements were concerned. Neither multipolar spindles nor pronounced cytoplasmic asters appeared in oocytes of mice approaching the end of their reproductive life (9 months and older). Oocytes of aged females also did not exhibit any sign of premature separation of parental chromosomes at prophase, obvious malorientations of bivalents, or significant lagging of chromosomes during ana- and telophase. Metaphase I with all bivalents aligned at the spindle equator appeared to be a relatively brief stage in oocyte development compared with pro- and prometaphase. Therefore, already slight disturbances occurring in the timing of the developmental programme which leads to a premature anaphase transition may be responsible for the high incidence of chromosomally unbalanced gametes in aged females, rather than non-separation and lagging of chromosomes during late ana- and telophase. In a second set of experiments we compared the metaphase II spindles of spontaneously ovulated oocytes obtained from animals at different ages. Previous studies have shown that spindle length and chromosome alignment may be altered in cells predisposed to aneuploidy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1988

The number of clonal precursors of the follicular epithelium in the mouse ovary.

The number of clonal precursors of granulosa cells in mouse ovarian follicles has been estimated using a technique based on the phenomenon of random X-chromosome inactivation of somatic cells and the use of an X-linked alloenzyme variant of the glycolytic enzyme PGK-1. The granulosa cells of follicles were oligoclonal in origin and founded by a small number of cells (about 5) which was consistent with histological observations. When the analysis was extended to two subcompartments of the follicle, the mural and cumulus granulosa cells, the results indicated that the cumulus and mural granulosa cells had a common origin.

Animals↗
PubMed1987

Follicular status at the menopause.

The store of ovarian follicles which is formed before birth progressively diminishes as a result of follicle death (atresia) and recruitment towards ovulation and will become barren in time. Depletion has occurred in the human ovary at or shortly after the menopause bringing reproductive potential, which has been declining for several years, to a final halt. Several factors can affect the timing of menopause and it appears that changes in the rates of follicle death have a greater impact than differences in the initial numbers of follicles. It is argued that the precocious loss of fecundity in humans, as compared with virtually all animals, has arisen adventitiously as a consequence of the evolution of long life relative to body weight.

Female↗