Biomedical subjects

J P Hearn

Publications and source records attributed to J P Hearn.

At least 19 recordsLinked to original sources

PubMed1992

Stimulation of immunoreactive inhibin production by preimplantation embryos during early pregnancy in the marmoset monkey (Callithrix jacchus).

The role of the embryo in promoting increased plasma concentrations of immunoreactive inhibin after conception in the marmoset monkey was determined by flushing embryos from the uterus between days 5 and 9 after ovulation (implantation commences on days 11-12). Blood samples were taken from each animal (three times a week) after ovulation until the end of the luteal phase. Plasma inhibin concentrations were measured using a radioimmunoassay based on antisera against a synthetic fragment of the alpha-subunit of human inhibin. When embryos were flushed on days 5 and 6 (n = 6) after ovulation inhibin concentrations did not exceed 250 ng ml-1 for the duration of the luteal phase. In contrast when embryos were flushed on days 7 (n = 4), 8 (n = 4) and 9 (n = 3) maximum concentrations of inhibin always exceeded 250 ng ml-1, reaching > 400 ng ml-1 when embryos were flushed on days 8 and 9. Inhibin concentrations remained high for the duration of the luteal phase, which varied in length between 20 and 32 days. Significantly (P < 0.01) higher mean plasma concentrations of immunoreactive inhibin were first recorded on days 7-8 after ovulation in animals that had embryos flushed on days 7, 8 and 9 compared with concentrations in animals that had embryos flushed on days 5 and 6. Inhibin could not be detected in the medium of embryos cultured for up to 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Chorionic gonadotrophin and embryo-maternal recognition during the peri-implantation period in primates.

Genes for chorionic gonadotrophin (CG) are transcribed by the 16-cell embryo stage in humans, but there is no clear evidence of CG secretion as a bioactive dimer before attachment and trophoblast outgrowth stages of implantation. The studies summarized question the timing of CG expression and secretion, the possible roles of CG for intraembryonic differentiation and at the implantation site, and the recognition of this primate embryo-derived signal in support of the corpus luteum. The data suggest that the implantation window in primates may be broader than in non-primate species, where a closer synchrony between embryonic, tubal and uterine events appears to be necessary for embryonic survival. Some preliminary data concerning an association between peripheral thrombocytopenia, ovarian inhibin secretion and peri-implantation stages of embryo development indicate that an unknown embryonic signal may be secreted before bioactive CG can be detected.

Animals↗

PubMed1991

Comparison of the luteolytic action of gonadotrophin-releasing hormone antagonist and cloprostenol, and the ability of human chorionic gonadotrophin and melatonin to override their luteolytic effects in the marmoset monkey.

The effects of the luteolytic and luteotrophic agents cloprostenol, human chorionic gonadotrophin (hCG) and melatonin on the corpus luteum have been investigated in marmoset monkeys treated with an LHRH antagonist to reduce endogenous LH secretion. This has allowed the effects of these agents to be investigated in the absence of the principal endogenous luteotrophin. Administration of the LHRH antagonist ([N-acetyl-D beta Nal1-D-pCl-Phe2-D-Phe3-D-Arg6-Phe7-Arg8-D-Ala10]NH2-LHRH) or cloprostenol between days 7 and 11 after ovulation (preimplantation) resulted in luteolysis. A significant (P less than 0.05) decrease in progesterone concentrations had occurred by 4 h after administration of the LHRH antagonist and was indeed preceded by a fall in LH concentrations. Coadministration of hCG with the LHRH antagonist prevented the fall in progesterone. In contrast, administration of cloprostenol resulted in an immediate fall in progesterone concentrations, to less than half the initial level within 1 h, and co-administration with hCG did not prevent the fall. Administration of hCG stimulated progesterone production when given 8 h after the LHRH antagonist but not after 24 h. Cloprostenol prevented the stimulation by hCG. Co-administration of melatonin with the LHRH antagonist did not prevent the decrease in progesterone concentrations. Melatonin was also not effective in preventing the fall in progesterone induced by cloprostenol. However, co-administration of melatonin and cloprostenol between days 17 and 21 after ovulation (post-implantation) significantly (P less than 0.05) delayed the fall in progesterone seen with cloprostenol alone. These results suggest that while the LHRH antagonist and cloprostenol have different sites of action their effect is similar at the corpus luteum, that is in depriving the corpus luteum of luteotrophic support. The results also suggest that melatonin may be able to influence the luteolytic action of cloprostenol but that its effect varies with the stage of the cycle. The physiological role for such an action, if any, remains unknown.

Animals↗

PubMed1990

Specificity of rheumatoid factors in relation to the disease state in rheumatoid arthritis.

Rheumatoid factors found in patients with rheumatoid arthritis react with human IgG and with IgG from some other species. The levels of rheumatoid factor give some indication of prognosis, albeit a rather poor one in this highly variable disease. The high degree of variability may, in part, be due to differences in the fine specificity of the rheumatoid factor in each individual patient, leading to differences in the types of immune complex formed. To study this hypothesis the fine specificity of rheumatoid factors of the IgM, IgA, and IgG classes for IgG from human, baboon, orangutan, macaque, owl monkey, gorilla, marmoset, cow, pig, sheep, goat, horse, mouse, and chicken was examined. Differential reactivity for these species was found and associations between the presence of rheumatoid factor and the development of moderate or severe erosions.

Animals↗

PubMed1990

Size distribution of luteal cells from pregnant and non-pregnant marmoset monkeys and a comparison of the morphology of marmoset luteal cells with those from the human corpus luteum.

The size distribution of marmoset luteal cells was determined on Days 6, 14 and 20 after ovulation in non-pregnant cycles and in early pregnancy. Image analysis was used to estimate the cell diameter of dispersed cells prepared from the marmoset corpus luteum (CL). Steroidogenic cells showed a size distribution consistent with one population of cells. There was a significant increase in mean cell diameter (P less than 0.05) from Day 6 to Day 14 in pregnant and non-pregnant animals with no further increase on Day 20. Micrographs of marmoset luteal tissue showed cells of greater than 10 micron containing the organelles typical of steroid-producing cells, and smaller non-steroidogenic cells surrounding the steroid-producing cells. On the basis of microscopy, there were no areas within the CL where cell composition was noticeably different. In contrast, micrographs of human luteal tissue showed two types of steroidogenic cell; most cells were similar to those in the marmoset CL but a smaller population of smaller cells could be distinguished around the periphery and along vascular septa. It is likely that these smaller and larger types of steroidogenic cells are of theca and granulosa cell origin respectively, the two cell populations differing in the degree of electron density and amount of rough endoplasmic reticulum. A distinguishing feature between marmoset and human luteal cells was the shape of the mitochondrian which were considerably rounder in marmoset luteal cells. The origin of steroidogenic cells in the marmoset CL is unclear, although in marmosets and man the luteal cell types display morphological characteristics distinct from the large and small luteal cells described for CL of the domestic ungulates.

Animals↗

PubMed1989

Changing responsiveness of luteal cells of the marmoset monkey (Callithrix jacchus) to luteotrophic and luteolytic agents during normal and conception cycles.

Dispersed marmoset luteal cells were incubated for 2 h and progesterone production measured after exposure to hCG, cloprostenol, dibutyryl cAMP, PGF-2 alpha, PGF-2, adrenaline or melatonin. The cells were studied on Days 6, 14 and 20 after ovulation in conception and non-conception cycles. Luteal cells from Day 14 non-pregnant marmosets were compared with human luteal cells taken in the mid-luteal phase. All the treatments stimulated progesterone production including cloprostenol, which is luteolytic when administered to the marmoset in vivo, but the degree of response varied with the stage of the cycle or pregnancy and between marmoset and human luteal cells. In the marmoset, overall analysis of the effect of the treatments showed that, on Day 6 after ovulation, there was no significant effect of any of the treatments in cells from pregnant or non-pregnant animals. In contrast, luteal cells from non-pregnant animals on Day 14 showed a significant response to the treatments (F (8,41) = 2.79, P less than 0.0145) whereas cells from pregnant Day-14 animals were responsive; in cells from pregnant animals, the control production of progesterone was high and already equivalent to the levels stimulated by the treatments. By Day 20, cells from pregnant animals produced lower control concentrations of progesterone than did those on Day 14 and there was a significant overall effect of the treatments (F (8,33) = 3.78, P less than 0.003). These results show that the marmoset CL gains responsiveness to treatment between Days 6 and 14 after ovulation in the non-pregnant cycle. In pregnancy, on Day 14, 2 days after attachment of the embryo, the high control concentrations of progesterone and absence of response to treatment suggest that an embryo message may have affected the CL, providing an endogenous stimulus.

Animals↗

PubMed1988

Births following the transfer of cultured embryos obtained by in vitro and in vivo fertilization in the marmoset monkey (Callithrix jacchus).

The aim of this study was to determine whether marmoset monkeys are a suitable primate model for in vitro fertilization (IVF), embryo culture, and transplantation studies. A prostaglandin analogue given in early pregnancy and human chorionic gonadotropin given near the end of the ensuing follicular phase were used for controlling the reproductive cycle, timing oocyte collection, and synchronizing the cycles of oocyte donors and embryo recipients. Five embryos obtained by IVF were transferred at early stages to the uterus of three recipients, and two gave birth to live infants. Some of the embryos were cultured to advanced blastocyst stages. In vivo fertilized oocytes were also cultured and transferred to two recipients, and one gave birth. We concluded that the marmoset is one of the best primates for such investigations.

Animals↗

PubMed1988

Stimulation of progesterone secretion by cultured human granulosa cells with melatonin and catecholamines.

Granulosa cells, aspirated from the follicles of patients undergoing treatment for in-vitro fertilization, were cultured in serum-supplemented medium. Adrenaline and noradrenaline stimulated a dose-related increase in progesterone secretion with a maximum stimulation at 10(-5) M, a response that was prevented by the beta-antagonist, propranolol. Adrenaline and hCG showed similar characteristics in their stimulation of progesterone secretion but there was no further increase in progesterone when the 2 compounds were added together. Melatonin stimulated progesterone secretion and, like adrenaline, this stimulation was prevented by propranolol. The ability of both adrenaline and melatonin to increase progesterone secretion was dependent on the degree of follicular development, as determined by peripheral oestradiol concentrations, on the day of laparoscopy. These results suggest that adrenaline and melatonin may have a physiological role in modulating luteal function and that melatonin may act by a beta-adrenergic-related mechanism.

Cells, Cultured↗

PubMed1988

Early secretion of chorionic gonadotrophin by marmoset embryos in vivo and in vitro.

The control mechanisms of early pregnancy in primates differ from those in non-primate species in the early secretion of chorionic gonadotrophin (CG) by the embryo and in the support of the corpus luteum. This study describes the initiation of secretion of CG by the embryo of the marmoset monkey examined in vivo and in vitro. A bioassay for gonadotrophin, which did not distinguish between CG and LH, was adapted and validated for the marmoset. A system of embryo culture was developed whereby embryos were grown from morula/blastocyst stages until at least the differentiation of the trophoblast and yolk sac, facilitated by the embryo attaching to a monolayer of marmoset fibroblast cells. Gonadotrophin concentrations were measured in the peripheral circulation of marmosets during precisely timed stages during the first 84 days of the 144-day gestation period, providing a profile of secretion that was maintained at high levels for longer than the profile seen in Old World primates, including man. A clear increase above baseline levels was seen by day 17 after ovulation, implantation commencing in the marmoset on days 11-13. Gonadotrophin was secreted by embryos in culture from the time of attachment in vitro, but there was no clear evidence of secretion before attachment. Levels of gonadotrophin secreted by embryos in vitro increased rapidly, reaching a maximum mean production rate of 90 mIU/24 h within 4 days after attachment. The experimental systems developed here will allow the examination of the local function of CG at the implantation site, intra-embryonic control of its secretion and its possible involvement in embryonic development.

Animals↗

PubMed1988

Embryonic signals during the peri-implantation period in primates.

During the peri-implantation period of pregnancy in primates, chorionic gonadotrophin (CG) is the first clear signal of the embryo's presence and viability. In the marmoset (Callithrix jacchus) implantation begins on Day 11-12 after ovulation and CG is secreted by the embryo from this time. The inner cell mass is necessary for the normal secretion of CG by the trophoblast. Implantation can be disrupted both in vivo and in vitro by antisera to the hCG-beta subunit. The secretion of a platelet activating factor by the preimplantation embryo has yet to be confirmed, as has the physiological function of this and other preimplantation signals. Local sampling by perfusion of the corpus luteum allows a direct measurement of the interactions between luteotrophins and luteolysins, as well as a method of screening potential new agents for regulating the function of the corpus luteum.

Animals↗

PubMed1987

The ultrastructure of early implantation in the marmoset monkey (Callithrix jacchus).

The ultrastructural morphology of the initial stages of implantation in the marmoset monkey (Callithrix jacchus) was studied in pregnant monkeys at known time intervals after ovulation. The earliest samples, obtained 13 days after ovulation, displayed both cytotrophoblast and syncytiotrophoblast. The cytotrophoblast was restricted to the blastocoel, whilst syncytiotrophoblast intruded to the endometrial basal lamina. At later stages, days 16 and 19 after ovulation, both cytotrophoblast and syncytiotrophoblast had extended laterally around the uterus, and the syncytiotrophoblast also extended deeper into the maternal tissues. The mesoderm layer was first discernible at 19 days after ovulation. At 23 days after ovulation the syncytiotrophoblast surrounded the maternal blood vessels entirely. In this study syncytiotrophoblast was not observed to breach the maternal blood vessels, even at 31 days after ovulation. Early cytotrophoblast columns could be seen at 31 days after ovulation. The endothelial cells lining the maternal blood vessels displayed hypertrophy from the earliest stages (day 13) onwards, although a true decidual response was only observed in samples of 23 and 31 days after ovulation.

Animals↗

PubMed1987

Partial purification and characterization of chorionic gonadotrophin in plasma and in culture medium of trophoblast cells from the marmoset monkey (Callithrix jacchus).

A biologically active gonadotrophin has been purified from the media of long-term cultures of trophoblast cells of the common marmoset monkey by a combination of precipitation and chromatography. Marmoset chorionic gonadotrophin (CG) is a glycoprotein which binds Concanavalin A and wheat germ agglutinin. The protein purified from culture media exists as several isoelectric species with pI in the range pH 3.5-4.5. On gel filtration it eluted with an apparent molecular weight of 68-72,000 but on PAGE migrated as if it was 58-65,000. A glycoprotein with similar characteristics has been recovered from plasma samples of pregnant marmosets. Biological activity of partly purified CG from media, as determined by a mouse testicular cell bioassay, was 1-3 i.u./mg protein.

Animals↗

PubMed1979

Characterisation of the immunological response in marmoset monkeys immunised against hCG beta-subunit and its relationship with their subsequent fertility.

Female marmoset monkeys that are actively immunised against hCG beta-subunit remain infertile while antibody titres are high. With declining antibody levels the animals experience recurrent abortions that occur progressively later as the levels continue to wane. After booster immunisations the animals become infertile once more. The affinity and total binding sites of antibodies to beta-hCG were monitored after booster injections in marmosets and the values were correlated with subsequent reproductive events. The relationship between antibody amount and affinity varied considerably and the affinity was the important factor in producing the biological effects, pregnancies being often associated with a fall in antibody affinity. The antisera were also biologically active in inhibiting hCG-induced ovulation and increase in uterine weight in mice. There was no apparent cross-reaction between the antisera and human luteinizing hormone as tested by indirect immunofluorescence on adult human pituitary sections.

Abortion, Incomplete↗

PubMed1979

Pregnancy diagnosis in the common marmoset (Callithrix jacchus jacchus).

Abdominal palpation of the uterus was carried out on 25 pregnant and 29 non-pregnant marmosets (Callithrix jacchus jacchus). 195 complete 24-hour urine specimens, collected between the first week of gestation and term (21 weeks), were tested with the Sub-Human Primate Tube (SHPT) test. No significant differences between the two methods in their ability to diagnose pregnancy were obtained between the first and 13th week of gestation. The SHPT test was seldom positive after the 13th week of pregnancy, whereas, with one exception, palpation always indicated pregnancy.

Animals↗

PubMed1979

'Collaborative' rearing of marmoset triplets.

A system of management is described in which all 3 offspring from triplet births to Callithrix jacchus can be successfully reared to weaning. Hand-rearing techniques are applied to the offspring in turn without depriving them of the maternal and family influences necessary for normal behavioural development.

Animals↗

PubMed1979

Peripheral plasma levels of progesterone, oestradiol-17 beta, oestrone, testosterone, androstenedione and chorionic gonadotrophin during pregnancy in the marmoset monkey, Callithrix jacchus.

Concentrations of LH/CG, androstenedione and testosterone rose in early pregnancy to maximum values at 6--10 weeks. Thereafter LH/CG levels declined and androstenedione and testosterone levels remained at plateau values or declined until term. Progesterone, oestradiol-17 beta and oestrone increased after ovulation and remained high throughout pregnancy. At 12 weeks, when LH/CG levels were falling, progesterone and oestradiol rose well above the luteal-phase levels which were maintained for the first 12 weeks. Progesterone declined in the 2 weeks before birth, while oestradiol and oestrone remained high. Pregnancies of an unknown stage were dated by reference to a graph of uterine diameter, measured by abdominal palpation, in animals at known times after conception. Measurement of progesterone concentrations during the conception cycle gave more accurate dating and showed that the gestation length was 144 days.

Androstenedione↗

PubMed1978

Immunological interference with the maternal recognition of pregnancy in primates.

If chorionic gonadotropin is involved, as part of the luteotrophic stimulus, in the maternal recognition of pregnancy in primates, then immunization against the beta subunit of hCG should prevent a conception going beyond the length of the normal cycle. Immunization against hCG-beta suppresses fertility in marmoset monkeys, baboons and rhesus monkeys, as long as the antibody titres remained high. As titres decline, however, female marmosets experience recurrent abortions interspersed with occasional live births. Young marmosets born to mothers with low circulating levels of antibody reach apparently normal sexual maturity. Immunization against hCG-beta subunit may have potential as a possible long-term method of fertility control in humans, but its reversibility needs further study. There is still a lack of basic knowledge of the functions of chorionic gonadotropin, especially now that its restriction to pregnancy seems improbable. Immunization against hCG may be valuable as a research tool with which to study the immunological relationships between mother and fetus during early pregnancy.

Animals↗

PubMed1978

A positive feedback effect of oestradiol on LH release in the male marmoset monkey, Callithrix jacchus.

Subcutaneous injections of oestradiol benzoate in oil, resulting in a sustained elevation of circulating oestradiol levels, induced an initial suppression of LH secretion, followed by a positive discharge of LH in castrated male and female and in intact male marmosets. Oestrogen-induced LH release (producing maximum LH concentrations 24 h after the injection) was observed in 75% of castrated males and females. A positive discharge of LH occurred in 50% of intact males 28-36 h after oestrogen administration.

Animals↗