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Claus Yding Andersen

Publications and source records attributed to Claus Yding Andersen.

18 recordsLinked to original sources
PubMed2006

Reduced fertility and inability of oocytes to resume meiosis in mice deficient of the Lxr genes.

Cholesterol precursors act as activators of the nuclear hormone receptor, liver X receptor (LXR). One of these LXR-activating ligands is meiosis activating sterol (MAS), which also induces resumption of meiosis in oocytes from mice in vitro. Whether LXR participates in the regulation of oocyte maturation and whether the expression of either one of the two paralogues of LXR (alpha and beta) affect fertility of mice has, however, not yet been clarified. Female mice lacking Lxra, Lxrb or both genes (Lxra(-/-), Lxrb(-/-) and Lxrab(-/-), respectively) conceive less frequently and have significantly fewer pups per litter as compared to wild type mice. Both Lxra and Lxrb mRNA were found to be expressed in mouse oocytes. The relative expression of, in particular, Lxrb was almost two orders of magnitude higher than in liver, brain and testis. A water-soluble LXR agonist caused naked oocytes, but not cumulus enclosed oocytes (CEO), from wild type mice to resume meiosis significantly more often than control oocytes. Follicle stimulating hormone (FSH) is a potent stimulator of meiosis in CEO from wild type mice, but was without effect in mice lacking both Lxr genes. Zymosterol, a MAS active substance, induced resumption of meiosis in oocytes from Lxrab(-/-) mice, but significantly less effectively than in oocytes from wild type mice. Taken together, LXRs seem to affect ovarian function, suggesting specific roles of cholesterol precursors in regulation of female reproduction.

Animals↗
PubMed2006

Estradiol and regulation of anti-Müllerian hormone, inhibin-A, and inhibin-B secretion: analysis of small antral and preovulatory human follicles' fluid.

CONTEXT: In ovaries surgically removed for fertility preservation, hormone concentrations in fluid from small antral follicles were determined. Levels were compared with those found in preovulatory follicular fluid. OBJECTIVE: The objective of this study is to measure intrafollicular concentrations of anti-Müllerian hormone (AMH), inhibin-A, inhibin-B, estradiol, and progesterone. SETTING: The study was set in a university hospital. PATIENTS: Patients were 22 women suffering from a cancer disease and 16 women undergoing assisted reproduction. INTERVENTIONS: Fluid from 35 follicles (diameter, 3-8 mm) was included and compared with that of 32 preovulatory follicles. MAIN OUTCOME MEASURES: The main outcome measures were intrafollicular concentrations of the measured hormones and their possible correlation. RESULTS: Concentrations of AMH in small antral follicles were almost three orders of magnitude higher than in follicle fluid of preovulatory follicles, 790 +/- 95 vs. 1.17 +/- 0.14 ng/ml (mean +/- sem), respectively. There was a significant negative correlation between estradiol and AMH in fluid from small antral follicles, whereas inhibin-A and inhibin-B were correlated positively with estradiol concentrations. Progesterone showed a similar correlation to levels of AMH but only in fluid of preovulatory follicles. CONCLUSIONS: The high expression of AMH in granulosa cells of small antral follicles actually translates into very high follicle fluid AMH concentrations. This most likely explains the correlation between serum AMH levels and the number of small antral follicles as previously demonstrated. The negative correlation between estradiol and AMH suggests that FSH down-regulates AMH expression. Thus, the microenvironment of the follicle shows profound changes with developmental stage and highlights the importance of studies to understand the mechanisms that regulate follicular growth and development during antral stages of development.

Adolescent↗
PubMed2006

Ovulation jumping from the left to the right ovary in two successive cycles may increase the chances of pregnancy during intrauterine insemination and/or in vitro fertilization natural cycles.

Identification of the ovary from which ovulation takes place in two consecutive menstrual cycles results in one of four ovulation patterns, contralateral and ipsilateral ovulations on the right or on the left ovary. Our data suggest that IVF and IUI treatment in cycles in which development of the dominant follicle occurs in the right-sided ovary--and ovulation took place from the left-sided ovary in the preceding cycle (contralateral right-sided ovulation)--is likely to show the best pregnancy outcome.

Female↗
PubMed2006

Genetic and environmental correlates of semen quality: a twin study.

BACKGROUND: The influences of environmental factors on the male reproductive system have been much debated over the last 3 decades. We studied the impact of genes and environment on semen quality, sex hormone levels, and sperm chromatin stability by using a twin design. METHODS: The study population consisted of monozygotic and dizygotic twins from the population-based Danish Twin Registry and a random selection of pairs of singleton brothers from the Danish Civil Registration System. All men were 20 to 45 years of age. The study population comprised 100 monozygotic twin brothers (50 pairs), 102 dizygotic twins (51 pairs), and 102 single-born brothers (51 pairs). A semen sample and blood sample were collected from all participants. RESULTS: Heritability was estimated to account for 20% (95% confidence interval = 0% to 68%) of the variation in sperm density. A higher heritability was found for the hormones reflecting Sertoli cell function (inhibin B, 76% [36% to 84%] and follicle-stimulating hormone, 81% [40% to 88%]) and for percent morphologic normal cells (41% [0% to 60%] and sperm chromatin parameters (mean alphaT, 68% [34% to 81%] and COMP alphaT, 72% [25% to 82%], respectively). CONCLUSION: Our study indicates a substantial hereditary component in plasma levels of hormones reflecting Sertoli cell function and in sperm cell chromatin stability and morphology. The environmental contribution (including the prenatal environment) appeared to be largest for sperm count.

Adult↗
PubMed2005

Eggs forever?

A group of scientists from Harvard Medical School (Johnson et al., 2004) claims to have "established the existence of proliferative germ cells that sustain oocyte and follicle production in the postnatal mammalian ovary," expressing no doubts about their methods, results and conclusion. Johnson et al. based their conclusions of oocyte and follicular renewal from existing germline stem cells (GSC) in the postnatal mouse ovary on three types of observations: (1) A claimed discordance in follicle loss versus follicle atresia in the neonatal period and in the following pubertal and adult period; (2) immunohistochemical detection of proliferating GSC with meiotic capacity using combined markers for meiosis, germline, and mitosis; and (3) neo-folliculogenesis in ovarian chimeric grafting experiments with adult mice. Oogenesis is the process that transforms the proliferative oogonium into an oocyte through meiosis, followed by folliculogenesis and follicular and oocyte maturation. The most crucial part in producing a functional oocyte is firstly, initiation and completion of the first meiotic prophase, and secondly, enclosure of the resulting diplotene oocyte in a follicle. Neither of these two events has been shown to take place in Johnson et al.'s study of the postnatal mouse ovary. We hereby address the observations underpinning their hypothesis and conclude that it is premature to replace the paradigm that adult mammalian neo-oogenesis/folliculogenesis does not take place.

Animals↗
PubMed2005

Urofollitropin and ovulation induction.

Anovulation is a common cause of female infertility. Treatment for women with anovulation is aimed at induction of ovulation. Ovulation induction with follicle-stimulating hormone (FSH) is indicated in women with WHO type II anovulation in whom treatment with clomifene citrate (clomifene) has failed. The majority of these women have polycystic ovary syndrome. The major disadvantages of ovulation induction with FSH are the risk of ovarian hyperstimulation syndrome and the risk of higher order multiple pregnancies. To reduce the rate of complications due to multiple follicular development, FSH should be administered using a chronic low-dose protocol with small dose increments. In women with WHO type I anovulation, an exogenous supply of luteinizing hormone (LH) is required to achieve an adequate follicular response to FSH treatment. Thus, ovulation induction with FSH is not the treatment of choice in these women. FSH is a hormone that stimulates follicle growth and oocyte maturation. Endogenous FSH is produced by the pituitary gland and exists as a family of isohormones exhibiting distinct oligosaccharide structures. FSH for exogenous administration is derived from urine or is produced as recombinant FSH. The commercially available FSH products all contain different mixtures of FSH isoforms. To determine the effectiveness of urofollitropin (urinary-derived FSH), a comparison with the other available gonadotropins was made (i.e. recombinant FSH and human menopausal gonadotropin). Urofollitropin and recombinant FSH appear to be equally effective and well tolerated for ovulation induction. Human menopausal gonadotropin is comparably effective to urofollitropin in terms of pregnancy outcomes. It remains unclear whether human menopausal gonadotropins have a higher risk of overstimulation and ovarian hyperstimulation syndrome compared to urofollitropin in women with polycystic ovary syndrome. In practice, recombinant products are more convenient to use but are also more expensive. Therefore, if availability is not an issue but costs are, there is still a place for the use of urofollitropins for ovulation induction.

Anovulation↗
PubMed2004

Roles of gonadotropins and meiosis-activating sterols in meiotic resumption of cultured follicle-enclosed mouse oocytes.

This study describes a model for short-term culture of intact mouse follicles under serum-free conditions. Follicles were either obtained from immature mice receiving no ovarian stimulation (i.e. no eCG-primed protocol, group I) or from mice undergoing ovarian stimulation (i.e. eCG-primed protocol, group II). Follicles were grouped according to size (100-170, 180-200, 210-250, 260-350 and 360-400 microm, respectively) and cultured for 24h (group I) or for only 6h (group II). Induced meiotic resumption of follicle-enclosed oocytes were evaluated following stimulation with gonadotropins (i.e. FSH and hCG), AY9944-A-7, an inhibitor of Delta14-reductase, and RS-21745, an inhibitor of lanosterol 14alpha-demethylase; both enzymes affect synthesis of the meiosis activating sterols (MAS) that induce oocyte maturation. The frequency of oocyte degeneration was also recorded. In group I, FSH (10-200 IUl-1) and AY9944-A-7 (5, 25 and 50 microM) separately induced resumption of meiosis in oocytes derived from follicles with a diameter of 180-400 microm. hCG (1.0 and 10 IUml-1) exhibited a similar but weaker effect on oocytes present in follicles with a diameter of 260-400 microm. Irrespective of follicular diameter oocytes obtained from follicles in group II responded to hCG and FSH by resuming meiosis. FSH (50 IUl-1) alone or hCG (10 IUml-1) alone both increased the GVBD percentage of oocytes enclosed in follicles with a diameter 260-400 microm, but the response to hCG was not significant compared to control. FSH (50 IUl-1) combination with hCG (10 IUml-1) showed an additive effect raising the rate of GVBD after 6h culture. Addition of 50 or 100 microM RS-21745 was able to attenuate gonadotropins-induced resumption of meiosis to below background levels. In conclusion, the ability of FSH to induce meiotic resumption of follicle-enclosed mouse oocytes is correlated to follicle size, being most pronounced in larger follicles. hCG caused a similar but less pronounced effect. The ability of RS-21745 to inhibit and the ability of AY9944-A-7 to enhance oocyte maturation of follicle-enclosed oocytes support the concept of FSH employing MAS as a downstream signal transduction molecule for initiation of oocyte maturation in mice.

Aniline Compounds↗
PubMed2004

Orthotopic autotransplantation of cryopreserved ovarian tissue to a woman cured of cancer - follicular growth, steroid production and oocyte retrieval.

Cryopreservation of human ovarian tissue is now an option for cancer patients facing treatment with gonadotoxic regimes, as a means of preserving their fertility. So far, there have been only a few reports on autotransplantation of frozen-thawed tissue with regard to restoration of ovarian function. The present report describes a 32-year-old woman diagnosed with Hodgkin's lymphoma, who had cryopreserved ovarian tissue transplanted orthotopically after secondary ovarian failure due to chemotherapy. Only 8 weeks after transplantation, ultrasonography of the remaining ovary revealed two follicles with diameters of 10 and 15 mm. Concomitantly, circulating concentrations of oestradiol increased, while concentrations of gonadotrophins decreased. In the following months, the patient menstruated three times. Subsequent pituitary down-regulation with a gonadotrophin-releasing hormone (GnRH) agonist and ovarian stimulation resulted in development of one pre-ovulatory follicle from which a metaphase II oocyte was retrieved; however, this oocyte was unable to sustain further development after intracytoplasmic sperm injection (ICSI). Intrafollicular concentrations of oestradiol and progesterone suggested a normal luteinizing response of the follicle to human chorionic gonadotrophin stimulation. A 7-month follow-up revealed continued vivid follicular activity and normal oestradiol concentrations. In conclusion, cryopreserved human ovarian tissue restored ovarian function for several cycles and sustained development of mature oocytes in a woman cured of cancer.

Adult↗
PubMed2004

FSH isoform composition of commercial gonadotrophin preparations: a neglected aspect?

The clinical efficacy of commercial gonadotrophin preparations has been the subject of an intense debate during recent years. Arguments have primarily focused on the origin of FSH activity (urine versus recombinant derived) and whether the preparation included LH-like activity. FSH isoform composition has received little or no attention, and is usually considered to have negligible effect on clinical effectiveness. By presenting the available data on the FSH isoform composition of commercial gonadotrophin preparations, the present paper challenges this assumption. To evaluate whether the FSH isoform composition affected the efficacy of a product, a meta-analysis was performed that compared a preparation expressing an acidic isoform profile (urinary-derived Metrodin-HP) with a preparation rich in less acidic isoforms (recombinant derived Gonal F). A total of five randomized clinical trials that specifically compared these two preparations was identified and included in the analysis. All parameters relating to the direct effect of FSH on the follicle differed significantly in favour of the product rich in less acidic isoforms, while data on pregnancy outcome did not reach significance. The importance of the FSH isoform profile and whether the FSH is derived from urine or by recombinant technique is discussed in relation to clinical efficacy. It is suggested that the FSH isoform profile of commercial gonadotrophin preparations is of clinical importance and should be taken into account when evaluating efficacy.

Carbohydrates↗
PubMed2003

Effect of glucocorticoids on spontaneous and follicle-stimulating hormone induced oocyte maturation in mouse oocytes during culture.

Several studies have indicated that glucocorticoids are involved in maturation of mammalian oocytes. Recently, maturation of porcine oocytes in culture was shown to be inhibited by glucocorticoids in a time- and dose-dependent manner. In addition, levels of cortisol available for biological action in fluid of preovulatory follicles are higher than that present in circulation. The present study evaluates the effect of cortisol and dexamethasone on mouse cumulus enclosed oocytes (CEO) undergoing spontaneous- and FSH-induced maturation during a 24h culture period using breakdown of the germinal vesicle (GVBD) as end-point. FSH-induced oocyte maturation was studied using media containing 4.5mM hypoxanthine to maintain levels of cAMP elevated, whereas spontaneous oocyte maturation was studied in a medium without hypoxanthine. In the presence of FSH (25 IU/l) the rate of GVBD was significantly elevated compared to the control. Dexamethasone (1-20 microg/ml) in combination with FSH resulted in a rate of GVBD similar to FSH alone. Cortisol (0.1-10 microg/ml) resulted in a significant higher rate of GVBD in combination with a physiological concentration of FSH (10 IU/l) as compared to the control but similar to that caused by FSH alone. Nearly all CEO that matured spontaneously resumed meiosis irrespective of whether or not cortisol was present. In conclusion, these results indicate that glucocorticoids have little or no influence on the regulation of oocyte maturation in the mouse. Species differences between mouse and pig oocytes may exist.

Animals↗
PubMed2003

Do basal oestradiol and oestradiol:androgens and oestradiol:FSH ratios reflect pregnancy potential of women receiving intrauterine insemination during natural cycles?

The aim of this retrospective study was to evaluate whether basal hormone profiles could be related to the ability to achieve pregnancy in women receiving intrauterine insemination (IUI) treatment during their natural menstrual cycle. Serum hormone profiles on cycle day 3 of naturally menstruating women were assessed in a total of 163 treatment cycles (29 conceptional and 53 non-conceptional cycles of 27 women who became pregnant and 81 non-conceptional cycles of 33 women who did not become pregnant). Basal concentrations of LH, FSH and prolactin were similar between conceptional and non-conceptional cycles. In contrast, concentrations of oestradiol in conceptional cycles (38 +/- 26 pg/ml: mean +/- SD) were significantly higher than those in non-conceptional cycles (23 +/- 18 pg/ml) (P = 0.0003). Concentrations of androstenedione and testosterone were lower but not significantly so in conceptional cycles as compared with non-conceptional cycles. The ratios of oestradiol/androstenedione, oestradiol/testosterone and oestradiol/FSH were significantly higher in conceptional as compared with non-conceptional cycles (29, 2.3, 6.2 versus 17, 1.2, 3.6 respectively) (all P < 0.006). Thus, increased concentrations of oestradiol and increased oestradiol/androgens and oestradiol/FSH ratios already on day 3 of the natural menstrual cycle correlate with the likelihood of achieving conception during the following IUI treatment. Therefore, measurement of basal hormones, including androstenedione and testosterone, may be useful to assess the health status of the coming dominant follicle.

Adult↗
PubMed2003

A clinical study comparing PureSperm and SpermFilter for density gradient separation of human spermatozoa in assisted reproduction.

OBJECTIVE: To compare a new density gradient medium, SpermFilter, for purifying spermatozoa in assisted reproduction with the more established medium, PureSperm. DESIGN: Part 1, a multicenter study on 225 semen samples purified using either PureSperm (115 semen samples) or SpermFilter (110 semen samples). Part 2, a retrospective, single center study on a total of 898 assisted reproductive cycles (245 insemination cycles using husband semen, 58 insemination cycles using donor semen and 595 in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles. SETTING: Part 1, three fertility clinics in Denmark (two university-affiliated fertility clinics and one private clinic). Part 2, one university-affiliated fertility clinic in Denmark. MAIN OUTCOME PARAMETERS: Part 1, purity of purified spermatozoa (% motile), motility index and recovery of motile spermatozoa. Part 2, malformation and baby take-home rates (insemination cycles), fertilization, cleavage, implantation, malformation and baby take-home rates (IVF/ICSI cycles). RESULTS: No statistical differences were observed in any of the parameters investigated. CONCLUSION: SpermFilter is a valid alternative to PureSperm in assisted reproduction technology (ART).

Adult↗
PubMed2003

Does smoking during pregnancy affect sons' sperm counts?

BACKGROUND: There has been an apparent decline in sperm density during the last 5 decades in Denmark, a country in which women have among the highest rates of smoking in Europe. We examined semen quality and sex hormones in men in relation to their mothers' tobacco smoking during pregnancy. METHODS: Male participants were selected from the population-based Danish Twin Registry and the Danish Civil Registration System as part of a study on hereditary and environmental determinants of semen quality. From November 1999 to May 2000 we collected one fresh semen and blood sample from each of 316 men. Data on prenatal tobacco exposure were obtained for 265 of these men from a questionnaire filled in by their mothers. RESULTS: Adjusting for age, current smoking status and other factors, sperm density was 48% lower(95% confidence interval = -69% to -11) among sons of mothers who smoked more than 10 cigarettes per day during pregnancy. Total sperm counts and levels of inhibin-B were also reduced among this group, whereas follicular stimulating hormone levels were somewhat higher (16% increase; 95% confidence interval = -13% to 54%). These effects were not seen in the lower smoking category (1-10 cigarettes per day). CONCLUSIONS: High levels of smoking (> 10 cigarettes per day) during pregnancy may be a partial explanation for the apparent secular decline and the geographic differences in sperm counts.

Adult↗
PubMed2002

Parental periconceptional smoking and male: female ratio of newborn infants.

We assessed whether the smoking habits of parents around the time of conception affects the likelihood of the offspring being male or female. We found that the offspring sex ratio (male to female) was lower when either one or both of the parents smoked more than 20 cigarettes per day compared with couples in which neither of the parents smoked. We found the lowest sex ratio among children whose mothers and fathers both smoked more than 20 cigarettes per day (p<0.0001). Parental periconceptional smoking might be a contributing factor to a lower male to female sex ratio of offspring.

Adult↗
PubMed2002

Role of meiosis activating sterols, MAS, in induced oocyte maturation.

Meiosis of follicle enclosed oocytes is maintained in the prophase of the first meiotic division and oocytes do not spontaneously resume meiosis during oocyte growth and follicle development. Arrest of the meiotic process is most likely secured by the presence of follicular purines, e.g. hypoxanthine, which maintain high levels of cAMP in the oocyte and which also in vitro prevent oocytes from resuming meiosis. Only in response to the mid-cycle surge of gonadotropins will oocytes of preovulatory follicles overcome the meiosis arresting effect of hypoxanthine and resume meiosis proceeding to the metaphase of the second meiotic division. Morphologically, resumption of meiosis is observed by the disappearance of the oocyte's nuclear membrane (germinal vesicle), a process called germinal vesicle breakdown (GVB). The molecular mechanism down-stream to receptor activation by which the mid-cycle surge of gonadotropins induces oocytes to resume meiosis is, however, only partly understood. The oocyte itself lacks gonadotropin receptors and its action is mediated through the attached cumulus cells. In vitro it has been shown that FSH induces synthesis of a signal in the cumulus cells, which overcomes the meiosis arresting effect of hypoxanthine. We have shown that a group of sterols, meiosis activating sterols (MAS), induces oocyte maturation in vitro even in oocytes depleted of cumulus cells. MAS were identified as intermediates in the cholesterol biosynthesis between lanosterol and cholesterol. The two best characterized members of the MAS family are FF-MAS purified from human follicular fluid (4,4-dimethyl-5alpha-cholest-8,14,24-triene-3beta-ol) and T-MAS purified from bull testicular tissue (4,4-dimethyl-5alpha-cholest-8,24-diene-3beta-ol). The synthesis, quantification, localization and tissue-accumulation of MAS are reviewed. Several publications have documented the pharmacological effect of MAS in different species, including oocytes from mouse, rat and human. Conflicting results obtained by the use of sterol synthesis inhibitors, which prevent MAS-accumulation, are also discussed. Whether FSH actually uses MAS as a signal transduction molecule for inducing oocyte maturation and the mechanism by which MAS induce resumption of meiosis is currently unknown, but data to support that MAS is part of the FSH induced signal transduction pathway are presented.

Animals↗
PubMed2002

Progesterone and 17 alpha-OH-progesterone in concentrations similar to that of preovulatory follicular fluid is without effect on resumption of meiosis in mouse cumulus enclosed oocytes cultured in the presence of hypoxanthine.

Some intermediates in the cholesterol biosynthesis between lanosterol and cholesterol are capable of inducing resumption of meiosis in cultured mouse oocytes without the presence of gonadotropins. The mechanism by which these so-called Meiosis Activating Sterols (MAS) activate the meiotic process is unknown, and it is uncertain whether they participate in the physiological control of resumption of meiosis. Recently, it has been shown that accumulation of MAS occurs in a liver cell line and in rat testis tissue cultured in the presence of micromolar concentrations of progesterone and 17 alpha-OH-progesterone. Such high concentrations of progesterone and 17 alpha-OH-progesterone only occur in fluid of preovulatory follicles. In connection with the mid-cycle surge of gonadotropins, this may represent one mechanism whereby follicular accumulation of MAS takes place. In the present study, the effect of 10 micro M progesterone and 10 micro M 17 alpha-OH-progesterone on resumption of meiosis was evaluated using mouse cumulus enclosed oocytes (CEO) cultured in the presence of 4mM hypoxanthine. By the end of the 24-h culture period, the frequency by which oocytes had resumed meiosis was assessed by the determination of germinal vesicle breakdown (GVBD). Neither progesterone nor 17 alpha-OH-progesterone or a combination showed any effect on GVBD. In addition, progesterone and 17 alpha-OH-progesterone in combination with a sub-optimal dose of FSH (4 IU/l) did not affect GVBD. In conclusion, accumulation of MAS to an extent that allows resumption of meiosis to occur in CEO is unlikely to be induced by progesterone and 17 alpha-OH-progesterone or a combination.

17-alpha-Hydroxyprogesterone↗