Biomedical subjects

S F Lunn

Publications and source records attributed to S F Lunn.

At least 19 recordsLinked to original sources

PubMed2002

Structure of the corpus luteum in the ovulatory polycystic ovary.

BACKGROUND: Women with polycystic ovaries (PCO) have a wide spectrum of presentation from anovulation and amenorrhoea to apparently regular, ovulatory menstrual cycles. We have recently reported a subtle defect in steroidogenic function in the luteal phase in the latter and an increase in the number of degenerating corpora lutea (CL) were observed in ovulatory PCO (ovPCO) during dissection. The possibility was therefore investigated of differences in structure or degeneration in CL formed during ovulatory cycles in women with PCO. METHODS: This study compared the histology of the CL in ovPCO with that in the normal ovary. Corpora lutea were collected from nine normal ovaries (days 1-27 of the cycle) and from 13 women with ovPCO (days 5-38). RESULTS: Variations in the degree of regression, both in relation to onset of menses and between different areas within individual CL, were recorded in both groups. During development and regression no obvious differences were observed between either group apart from an apparent increase in luteal haemorrhage, which was more common and more extensive in CL from PCO. CONCLUSIONS: The findings suggest that possible luteal phase abnormalities of steroid secretion in women with ovulatory PCO are not associated with obvious morphological defects in the CL, however it is possible that the persistence of luteal structures seen in PCO was a consequence of increased luteal haemorrhage.

Corpus Luteum↗

PubMed2001

Luteal angiogenesis: prevention and intervention by treatment with vascular endothelial growth factor trap(A40).

The possibility of stimulating or inhibiting paracrine factors regulating angiogenesis may lead to new approaches for the treatment of pathological conditions of the female reproductive tract. We examined the effects of a clinical candidate, a soluble truncated form of the Flt-1 receptor, vascular endothelial growth factor trap(A40) (VEGF trap), in a primate model to determine its ability to prevent the onset of luteal angiogenesis or intervene with the on-going process. Marmosets were treated from the day of ovulation until luteal day 3 (prevention regimen) or on luteal day 3 for 1 day (intervention regimen). Effects of VEGF inhibition were studied by obtaining a proliferation index using bromodeoxyuridine incorporation, quantifying endothelial cell area using CD31, and assessing luteal function by plasma progesterone. After both treatments, intense luteal endothelial proliferation was suppressed, a concomitant decrease in endothelial cell area confirmed the inhibition of vascular development, and a marked fall in plasma progesterone levels showed that luteal function was compromised. In situ hybridization was used to localize and quantify compensatory effects on the expression of angiogenic genes. VEGF messenger ribonucleic acid (mRNA) expression in luteal cells was increased, whereas expression of its receptor, Flt, was decreased. Inhibition of VEGF resulted in localized increased expression of angiopoietin-2 mRNA and its receptor, Tie-2. The results show that the VEGF trap can prevent luteal angiogenesis and inhibit the established process with resultant suppression of luteal function. Luteal Flt mRNA expression is dependent upon VEGF, and VEGF inhibition results in abortive increases in expression of VEGF, angiopoietin-2, and Tie-2.

Angiopoietin-2↗

PubMed2001

Regulation and manipulation of angiogenesis in the primate corpus luteum.

Intense physiological angiogenesis occurs during the early stages of luteal development, providing a model in which the complex processes regulating the angiogenic pathway may be studied. Here, a working hypothesis is presented to explain the diverse changes in the vasculature of the corpus luteum that occur over a short period, based around changes in vascular endothelial growth factor, the angiopoietins and matrix metalloproteinases. An illustration is given of how angiogenesis can be monitored in a primate model and how the role of individual angiogenic factors such as vascular endothelial growth factor may be explored in vivo. Because of the marked effect of inhibition of angiogenesis on luteal function, it is predicted that the normal processes of follicular development, ovulation and luteal function could all be profoundly influenced by the manipulation of angiogenesis.

Animals↗

PubMed2000

Endocrine-immune interaction: alteractions in immune function resulting from neonatal treatment with a GnRH antagonist and seasonality in male primates.

PROBLEM: The effect of neonatal gonadotropin releasing hormone (GnRH) antagonist (Ant) treatment and seasonality on immune system development and function was investigated in male primates. METHOD OF STUDY: Neonatal male rhesus monkeys and marmosets were treated with Ant, and its effect on immune system morphology, circulating lymphocyte subsets, and cell- and humorally-mediated immune responses was assessed during development. In adult rhesus monkeys, we correlated seasonal changes in immune function with circannual fluctuations in immunoactive hormones. RESULTS: In neonatal marmosets, Ant reduced the number of B cells and T cells in the thymic medulla and T cells in the periarterial lymphatic sheaths (PALS) of the spleen. Ant also altered the development of, but did not permanently impair, the proliferative index (PI) of blood lymphocytes to mitogens. In vitro treatment of control lymphocytes with GnRH analogues altered their response to these proliferative agents. In neonatal rhesus monkeys, Ant treatment increased the frequency of clinical problems, lowered circulating levels of lymphocytes, total T cells, CD8+ T cells and B cells, and altered the PI of lymphocytes to mitogens. As adults, the cell- and humorally-mediated immune responses remained impaired. We also documented seasonal fluctuations in the prevalence of diseases, circulating immune cells and immune function in rhesus monkeys. The number of cases of campylobacteriosis and shigellosis was lowest in the winter and highest in the spring. Circulating numbers of white blood cells (WBC) and neutrophils and the PI of lymphocytes to mitogens were higher in the winter than in the summer. Natural killer cell activity also varied with season. Cortisol and leptin secretion exhibited circannual rhythms, rising in concert with decreasing photoperiod and increasing testicular activity in the fall. Conversely, prolactin levels declined with decreasing photoperiod and then rose in the spring. CONCLUSION: Neonatal exposure of male primates to Ant appears to alter early postnatal programming of immune function. In the rhesus monkey, immune function shows seasonal fluctuations that may be driven by circannual changes in the secretion of immunoactive hormones.

Animals↗

PubMed2000

Suppression of luteal angiogenesis in the primate after neutralization of vascular endothelial growth factor.

Manipulation of angiogenesis may have a profound effect on female reproductive function, but this has not yet been demonstrated by direct experiment in species with ovulatory cycles similar to those in women. To investigate whether angiogenesis could be inhibited in the primate corpus luteum, and the consequences of such inhibition on luteal function, marmosets were treated with an antibody to vascular endothelial growth factor (VEGF). Treatment commenced at the time of ovulation and was continued for 3 days (early luteal group) or 10 days (midluteal group). Bromodeoxyuridine was used to label proliferating cells, being administered 1 h before collecting ovaries from control and treated animals in the early or midluteal phase. Ovarian sections were stained using an antibody to bromodeoxyuridine, and a proliferation index was obtained; endothelial cell quantification was performed using factor VIII as an endothelial cell marker. Intense proliferation in the early luteal phase was suppressed by anti-VEGF treatment. This resulted in blockade of development of the normally extensive capillary bed, as in the animals treated until the mid-luteal phase the numbers of endothelial cells were reduced. The hormone-producing cells remained largely unaltered in the posttreatment corpus luteum, although the presence of lipid accumulation, and small pockets of cells showing basophilia and nuclear condensation were observed. Significantly, luteal function, as judged by secretion of progesterone, was markedly compromised by the treatment, being reduced by 60% in comparison with controls. It is concluded that VEGF-mediated angiogenesis is an essential component of luteal function in primates and therefore has the potential to be regulated.

Animals↗

PubMed2000

Changes in insulin-like growth factor-binding protein-3 messenger ribonucleic acid in endothelial cells of the human corpus luteum: a possible role in luteal development and rescue.

In the human menstrual cycle, extensive angiogenesis accompanies luteinization; and the process is physiologically important for corpus luteum (CL) function. During luteolysis, the vasculature collapses, and the endothelial cells die. In a conceptual cycle, the CL persists both functionally and structurally beyond the luteoplacental shift. Although luteal rescue is not associated with increased angiogenesis, endothelial survival is extended. Despite the central role of the luteal vasculature in fertility, the mechanisms regulating its development and demise are poorly understood. There is increasing evidence that insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) may be important effectors of luteal function. Here, we have found that IGFBP-3 messenger RNA is expressed in the endothelium of the human CL and that the levels of message change during luteal development and rescue by human CG. The signal was strong during the early luteal phase, but it showed significant reduction during the mid- and late luteal phases. Interestingly, administration of human CG caused a marked increase in the levels of IGFBP-3 messenger RNA in luteal endothelial cells that was comparable to that observed during the early luteal phase. We conclude that endothelial cell IGFBP-3 expression is a physiological property of the CL of menstruation and pregnancy. These observations raise the intriguing possibility that the regulated expression of endothelial IGFBP-3 may play a role in controlling angiogenesis and cell responses in the human CL by autocrine/paracrine mechanisms.

Adult↗

PubMed2000

Angiogenesis and its control in the female reproductive system.

The rapid, controlled and cyclical nature of angiogenesis in the female reproductive tract suggests that interference with this process should provide a novel approach to manipulation of reproductive function. Many factors involved in the regulation of angiogenesis have been identified, and the possibility of stimulating or inhibiting these paracrine control mechanisms is being addressed using current advances in the development of angiogenic and anti-angiogenic compounds. Studies with animal models indicate that the normal processes of folliculogenesis, ovulation and corpus luteum function in the ovary, and the control of menstruation and implantation in the endometrium could be profoundly influenced by manipulation of angiogenesis. Novel therapeutic agents targeted to the angiogenic pathway may also have a wide range of applications in pathological processes in the reproductive tract such as cancer, endometriosis, fibroid growth, and ovarian hyperstimulation syndrome.

Angiogenesis Inhibitors↗

PubMed1999

The effect of the angiogenesis inhibitor TNP-470 on luteal establishment and function in the primate.

Angiogenesis during luteal development is probably essential for normal lutein cell function. Since the angiogenesis inhibitor TNP-470 inhibits pregnancy in mice, the current study investigated its effects on the establishment and function of the primate corpus luteum. Regularly ovulating macaques were treated with TNP-470 (6 mg/kg), i.v. in three doses, 48 h apart. Serum progesterone concentrations, as indicators of treatment effect, were normal in four macaques where treatment commenced at the onset of the ovulatory progesterone rise, and in five of eight in which treatment commenced a few days before ovulation. In the other three the normal progesterone rise was absent. To investigate the direct effect on luteal angiogenesis of a daily dose over a longer period, four marmosets received 18 mg/kg/day of TNP-470 i.v. for 9 days starting at ovulation. On day 10, luteal cell proliferation was determined by nuclear bromodeoxyuridine incorporation. Luteal microvasculature was examined using immunocytochemical factor VIII staining, and endothelial cell and luteal function assessed by in-situ hybridization of insulin-like growth factor binding protein-3 mRNA and plasma progesterone concentrations respectively. None of these parameters were affected by the TNP-470 treatment. The results show that, with the treatment regimens employed, TNP-470 had no significant effect on the expression of the differentiated state of the primate corpus luteum.

Animals↗

PubMed1999

Luteal regression in the primate: different forms of cell death during naturaland gonadotropin-releasing hormone antagonist or prostaglandin analogue-induced luteolysis.

Morphological changes in the corpus luteum following natural and induced luteolysis in the marmoset were investigated by light and electron microscopy. Functional corpora lutea were studied in the mid and late luteal phase, naturally regressed corpora lutea in the early and late follicular phase, and corpora lutea induced to regress by administration of GnRH antagonist or prostaglandin F(2alpha) analogue in the midluteal phase. Natural luteolysis was associated with lutein cell atrophy, condensation of cytoplasmic inclusions and organelles, and accumulation of lipid. GnRH antagonist treatment resulted in aggregations of smooth membranes and myelin-like bodies in the cytoplasm of the lutein cells together with complex aggregations of degenerative cells. After prostaglandin treatment, the lutein cells contained numerous small and large vesicles; as the degenerative changes advanced, these vesicles coalesced into alveolar-type vacuoles, and nuclei involuted. These results show that in the marmoset, natural luteolysis and the two luteolytic treatments reveal different forms of luteal degeneration and cell death, none of which fit the ultrastructural criteria for apoptosis. More emphasis needs to be placed on understanding these predominant nonapoptotic forms of cell death in order to elucidate the process of luteolysis in the primate.

Animals↗

PubMed1999

Effect of neonatal treatment with a GnRH antagonist on development of the cell-mediated immune response in marmosets.

PROBLEM: We examined the effect of neonatal treatment with a gonadotropin-releasing hormone (GnRH) antagonist (antide) on the development of cell-mediated immunity in male marmosets. METHOD OF STUDY: Neonatal marmoset twins were treated with either vehicle or antide, and the proliferative response (PR) of lymphoid tissue to mitogens was assessed during infancy, the peripubertal period, and adulthood. RESULTS: Basal proliferation of peripheral blood mononuclear cells (PBMC) from treated peripubertal twins was elevated above control values, but the PR of the cells to T and B cell mitogens was subnormal. Conversely, PBMC from treated infants exhibited an enhanced PR to some of the mitogens employed. In vitro culturing of thymocytes (control or treated) from the three developmental stages with either antide or a GnRH agonist increased basal proliferation, but decreased the PR to mitogens by 60-80%. CONCLUSION: Neonatal treatment with antide alters development of, but does not permanently impair, cell-mediated immunity in the marmoset. GnRH appears to modulate immune responses throughout development in the primate.

Animals↗

PubMed1998

Insulin-like growth factor binding protein-3 mRNA expression in endothelial cells of the primate corpus luteum.

Luteinization is associated with endothelial cell proliferation as part of the extensive angiogenesis necessary to maintain corpus luteum function. However, following luteal demise, the vasculature regresses and the endothelial cells disappear. In the rat corpus luteum, the endothelial cells express high concentrations of insulin-like growth factor-binding protein-3 (IGFBP-3) during luteolysis, suggesting a role of IGFBP-3 during endothelial cell loss. The aim of the present study was to determine the occurrence and location of the messenger ribonucleic acid (mRNA) for IGFBP-3 in the primate corpus luteum, and to determine whether or not induction of luteal regression is associated with changes in localization of the message. Marmoset corpora lutea were studied throughout the cycle. The effects of induced luteolysis were examined 12 h or 24 h after treatment with either a gonadotrophin-releasing hormone antagonist or a prostaglandin F2alpha analogue, administered during the mid-luteal phase. High IGFBP-3 expression was recorded in the endothelial cells of the majority of microvessels and a minority of capillaries surrounding the lutein cells in all functionally active corpora lutea. Expression declined markedly in regressing corpora lutea of the late follicular phase. Expression of the IGFBP-3 mRNA in lutein cells in the control corpus luteum was extremely rare. There were no major differences in the degree and pattern of IGFBP-3 expression as a consequence of induced luteal regression although there was an apparent increase in the number of capillary endothelial cells expressing. Induction of luteolysis resulted in expression in a minority of lutein cells. These results support the concept that IGFBP-3 has an autocrine/paracrine role in regulating various cell types in the primate corpus luteum, including endothelial cells. However, expression of IGFBP-3 mRNA throughout the luteal phase suggests it may regulate angiogenesis and luteal function rather than endothelial cell death and luteolysis.

Animals↗

PubMed1998

Changes in lymphoid tissue after treatment with a gonadotropin releasing hormone antagonist in the neonatal marmoset (Callithrix jacchus).

PROBLEM: The effect of neonatal treatment with a gonadotropin releasing hormone (GnRH) antagonist on the morphology and distribution of lymphocytes in lymphoid tissue of the infant marmoset was examined. METHOD OF STUDY: From a screened panel of antihuman antibodies for specific immune cells, antibodies for the CD20 and CD3 antigens showed excellent reactivity with marmoset tissue. Five sets of marmoset twins were treated with either the GnRH antagonist or a vehicle from birth, and were euthanized at 7 to 9 (3 sets) or 16 to 20 weeks (2 sets) of age. The spleen, thymus, and inguinal lymph nodes from each animal were processed for immunocytochemistry, and the number of cells expressing the CD20 and CD3 antigens were quantified. RESULTS: Control twins exhibited high plasma levels of testosterone, characteristic of the neonatal period, whereas testosterone concentrations were reduced (P = 0.001) to detection limits in the GnRH antagonist-treated twins. Microscopic evaluation suggested that treatment reduced the volume and cellularity of the thymic cortex, resulting in a decrease in the cortical-to-medullary ratio. Treatment reduced (P = 0.046) the number of thymocytes expressing the B-cell antigen (CD20) and marginally lowered (P = 0.067) the number expressing the T-cell antigen (CD3) in the thymic medulla. In the spleens of treated animals, periarterial lymphatic sheaths were less prominent on microscopic examination, and there were marginally fewer (P = 0.064) CD3+ cells. Numbers of CD20+ lymphocytes in the peripheral white pulp of the spleen and in the germinal centers of the lymph nodes, or CD3+ cells in the paracortex and germinal centers of the lymph nodes, were not altered by treatment. CONCLUSION: Neonatal treatment with a GnRH antagonist may alter maturational processes for B and T cells in the thymus and spleen of the marmoset and may deprive the immune system of its normal sensitivity to GnRH at a potentially critical time in development.

Animals↗

PubMed1997

Initiation of high dose gonadotrophin-releasing hormone antagonist treatment during the late follicular phase in the macaque abolishes luteal function irrespective of effects upon the luteinizing hormone surge.

The determination of the efficacy of gonadotrophin-releasing hormone (GnRH) antagonists in blocking the luteinizing hormone (LH) surge and luteal function is important for our understanding of the control of the menstrual cycle and for clinical application. GnRH antagonists have failed to block the LH surge reliably in the non-human primate. The aim of the study was to utilize high dose GnRH antagonist treatment administered during the late follicular phase of the menstrual cycle to block the pre-ovulatory LH surge. It was postulated that the LH surge would be prevented in all animals, but if this failed subsequent luteal function would be blocked by continued suppression of LH, since the early corpus luteum is susceptible to inhibition by GnRH antagonist treatment. A group of 16 adult female stumptailed macaques (Macaca arctoides) with regular menstrual cycles were selected. The GnRH antagonist [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,D-(Hci)6, Lys(iPr)8,D-Ala10]GnRH (Antarelix) (concentration 10 mg/ml) was administered as three daily s.c. injections, at a dose of 1 mg/kg on days 11, 12 and 13 of the follicular phase of the menstrual cycle. Of nine macaques in which it was judged that the treatment was commenced within 1 day of the expected LH surge (serum oestradiol >400 pmol/l), six demonstrated a decline in serum oestradiol concentrations, a total block of the LH/follicle stimulating hormone (FSH) surge and inhibition of ovulation as judged by an absence of a rise in progesterone concentrations. In the three other animals in this category, a partial LH surge occurred, but this failed to result in a functional corpus luteum. In a further three animals treatment was initiated on the day of the LH surge, and again there was absence of a subsequently functional corpus luteum. These results show that GnRH is involved at the time of the mid-cycle LH/FSH surge in the non-human primate. Initiation of high dose GnRH antagonist treatment during the periovulatory period abolishes luteal function irrespective of its effects upon the LH surge because of its long-term action and resultant withdrawal of luteal support.

Animals↗

PubMed1997

Cell death during luteal regression in the marmoset monkey (Callithrix jacchus).

The mechanism controlling luteal regression in primates is unknown but may involve cell death by apoptosis. Marmoset ovaries containing corpora lutea were studied at different stages of the normal ovarian cycle. Two additional groups of animals underwent induced luteolysis with either the prostaglandin F2 alpha analogue, cloprostenol, or the GnRH antagonist, antarelix, at the mid-luteal phase. Apoptosis in ovarian sections was estimated both by counting the number of cells exhibiting morphological features of apoptosis and by in situ labelling the 3' ends of the DNA fragments with digoxigenin-11-dUTP. Apoptosis was found to be significantly increased in corpora lutea in the early follicular phase (equivalent to the later stage of luteal lifespan) compared with the mid-luteal phase corpora lutea, as judged by either computerized morphometry or 3' end labelling. Apoptosis was also increased by the administration of either cloprostenol or antarelix when using the 3' end labelling end point, but only after cloprostenol when using computerized morphometry. A further form of cell death, characterized by the formation of cytoplasmic vacuoles, was also observed in corpora lutea undergoing both induced and spontaneous regression. These results demonstrate that apoptosis within the primate corpus luteum is increased in both physiological and induced luteal regression. In addition, they show that an alternative form of cell death is involved in both spontaneous and induced luteal regression, although the relative importance of the two mechanisms remains to be determined.

Animals↗

PubMed1997

Blockade of the neonatal increase in testosterone by a GnRH antagonist: the free androgen index, reproductive capacity and postmortem findings in the male marmoset monkey.

Male marmoset monkeys which had received gonadotrophin-releasing hormone (GnRH) antagonist treatment as neonates to block the postnatal increase in testosterone were studied, with the object of determining potential long-term effects of treatment on the reproductive system, including tests of fertilising capacity. To obtain information on the nature of the circulating testosterone during this neonatal period, sequential blood samples were collected from a further control group of ten neonates, aged between birth and 3 months, and from 11 adult, normally fertile males, to examine the relative proportions of free, sex-hormone-binding globulin (SHBG)-bound, and non-SHBG-bound testosterone. In control neonates, 11% of the circulating testosterone was free, and a further 19% non-SHBG-bound, and therefore presumed to be biologically available. The remaining 70% was SHBG-bound and considered to be biologically inert. This indicates that the neonatal increase in marmoset testosterone has a biological function. After pairing with females, time to first positive vaginal lavage and first delivery was similar for females, whether they were with control or treated male partners. Pregnancy outcome, in terms of number of young delivered and sex ratio, did not differ. This indicates that there appear to be no long-term sequelae in terms of procreative ability in male marmosets treated neonatally with a GnRH antagonist. Autopsy revealed no gross changes, except in the thymus, which was significantly heavier in the treated group. These results indicate that, although the circulating testosterone is in a biologically active form during the neonatal period, inhibition of testicular function in the neonate is without major effect on the adult male reproductive system. Treatment with a GnRH antagonist may have long-term effects on the immune system.

Animals↗

PubMed1995

Induced luteal regression: differential effects on follicular and luteal inhibin/activin subunit mRNAs in the marmoset monkey.

During the luteal phase of the primate ovulatory cycle the predominant inhibin/activin subunit mRNAs produced by the corpus luteum and antral follicles are those for the alpha- and beta B-subunits respectively. The control of expression of these mRNAs and the resultant nature of the endocrine and paracrine signals which they may potentially generate has yet to be elucidated. Inhibin/activin subunit mRNAs may have a role in both the paracrine regulation of follicular and luteal function and modulation of FSH secretion. The aim of this study was to investigate the expression of inhibin/activin subunit mRNAs following luteal regression induced by either withdrawal of LH support (GnRH antagonist treatment), or by a direct inhibitory action (prostaglandin administration). Marmoset monkeys with regular ovulatory cycles were treated on day 8 and 9 of the luteal phase with either GnRH antagonist, prostaglandin or vehicle (n = 3 per group). Ovaries were studied 48 h after onset of treatment (on day 10 of the luteal phase) by hybridizing frozen tissue sections with radiolabelled riboprobes specific to the inhibin/activin alpha-, beta A- and beta B-subunit mRNAs. After autoradiographic exposure, grain concentrations were quantified by image analysis. In corpora lutea from control marmosets there was high expression of alpha-mRNA with only marginal expression of beta B-mRNA. Corpora lutea in animals treated with GnRH antagonist or prostaglandin had markedly reduced expression of alpha-mRNA while beta B-mRNA was unchanged. In controls, all healthy antral follicles exhibited a high level of expression of beta B-mRNA in the granulosa cells and low expression of alpha-mRNA in theca cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Activins↗

PubMed1995

Induced luteal regression in the primate: evidence for apoptosis and changes in c-myc protein.

There is increasing molecular evidence that apoptosis is involved in the process of structural luteal regression in non-primate species. Apoptosis is dependent upon the activation of certain proto-oncogenes and c-myc protein has an important regulatory role in this process in some cell types. The aim of the present study was to determine the occurrence and localisation of c-myc protein within the primate corpus luteum, determine changes during induction of luteal regression and examine the corpora lutea for morphological evidence of apoptosis. Ovaries were studied from marmoset monkeys in the late follicular, and in the early, mid and late luteal phases. Luteal regression was induced either by treatment with prostaglandin F2 alpha analogue or GnRH antagonist administered during the mid luteal phase and ovaries obtained 24 and 48 h later. Immunocytochemistry was performed using a monoclonal antibody to the c-myc protein. In pre-ovulatory follicles positive staining was found in the nucleus of a few granulosal cells and in the cytoplasm of thecal cells. c-myc was present in all corpora lutea where it was localised predominantly in the cytoplasm. In early corpora lutea, scattered cells with intense staining were observed in the presence of a majority of moderately or weakly stained cells. In the mid and late luteal phases, corpora lutea were uniformly moderately stained for c-myc. Following induction of luteal regression, regression, nuclear degeneration with condensation and fragmentation indicative of apoptosis was observed. In other luteal cells, increased membranes suggested necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Gonadotropin-releasing hormone antagonist for postpartum contraception: outcome for the mother and male offspring in the marmoset.

GnRH antagonists have potential for use in postpartum contraception, as it is likely that they would be effective in maintaining the inhibition of ovulation associated with lactation, but possible effects on the infant by transfer of antagonist via breast milk are unknown. The aim of this study was to establish whether chronic treatment with a GnRH antagonist would prevent ovulation throughout the period of lactation using the marmoset monkey as a model and to evaluate the effects of the presence of GnRH antagonist in breast milk on the postnatal rise in plasma testosterone concentrations in male infants. Mothers who had delivered male twins were selected. Starting within 3 days postpartum, mothers (n = 5/group) were treated with either 6.0 or 0.6 mg/kg of the GnRH antagonist antide, sc, once per week for 11 weeks. Ten postpartum lactating females acted as controls. All animals were housed in family groups with fertile males. To determine possible effects on the postnatal rise in testosterone, plasma samples were collected from the male infants of the high dose antide-treated mothers at weekly intervals for 12 weeks. Plasma progesterone concentrations were monitored in lactating mothers until establishment of pregnancy in both treated and control groups. Concentrations of antide were determined by RIA in plasma from mothers in the high dose group, in their milk, and in pooled plasma samples from their infants. Ovulation followed by pregnancy occurred in all of the control animals. No ovulations occurred during treatment with antide. Antide was present throughout treatment in plasma and breast milk in the mother. In male infants feeding from mothers receiving high dose treatment, antide was not detectable in infant plasma, and plasma testosterone concentrations were within the normal range for male neonates in our colony. These results indicate that the GnRH antagonist has potential as a method of contraception postpartum without affecting the postnatal rise in testosterone in male infants.

Animals↗