| 61. |
- Murto, Tiina, 1975-, et al.
(författare)
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Socioeconomic and lifestyle factors in relation to folic acid supplement use in infertile and fertile Swedish women
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Socioeconomic and lifestyle factors are considered to be associated with folic acid supplement use and intake in the general population, but studies on infertile women are lacking. When investigating dietary supplement intake, the validity of the assessment of reported supplement use and actual intake is crucial. The objective of the study was to investigate socioeconomic, lifestyle and dietary factors in relation to folic acid supplement use and folate status in infertile and fertile women. In addition, a sub-analysis was performed to validate the used questionnaire. Methods: In this observational study, 340 infertile women and 188 fertile women were investigated. A questionnaire was used to assess lifestyle and dietary habits and use of dietary supplements. Blood samples were obtained for analyses of plasma folate and homocysteine levels. 24-hour recall interviews were performed to validate the questionnaire. Results: Folic acid supplement use was related to marital status, educational level and employment status. Infertile women had significantly higher mean folic acid daily intake and better folate status. However, folate status did not correlate with socioeconomic or lifestyle factors. The infertile women were physically more active, smoked less and had better employment status, but they were also more obese than fertile women. Socioeconomic and lifestyle factors were not related to in vitro fertilization outcome. Dietary data from the questionnaires showed good validity compared with the data from the 24-hour recall interviews, but data regarding folic acid supplement use showed only fair agreement between these methods. Conclusions: Highly educated, employed, married and infertile women were most prone to using folic acid supplements. Only a few socioeconomic and lifestyle factors differed between infertile and fertile women, and these were not related to folate status or IVF outcome. Methods other than a questionnaire are recommended when investigating folic acid supplement use.
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| 62. |
- Nordqvist, Sarah, 1962-
(författare)
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Biological Markers of Fertility
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Infertility affects 15 % of couples, which corresponds to 60 - 80 million worldwide. The microenvironments in which the oocyte, embryo and fetus mature are vital to the establishment and development of a healthy pregnancy. Different biological systems, such as angiogenesis, the immune system and apoptosis need to be adequately regulated for pregnancy to occur and progress normally. The overall aim of this thesis was to investigate the impact of Histidine-rich glycoprotein (HRG) and Src homology 2 domain-containing adapter protein B (SHB) on human female fertility.HRG is a plasma protein that regulates angiogenesis, the immune system, coagulation/fibrinolysis and apoptosis, by building complexes with various ligands. The impact of HRG on fertility is studied here for the first time. HRG is present in follicular fluid, the Fallopian tube, endometrium, myometrium and placenta. HRG distribution within embryo nuclei depends on developmental stage. Blastocysts express and secrete HRG. The HRG C633T single nucleotide polymorphism (SNP) appears to affect the chance of pregnancy and, correspondingly, parameters associated with pregnancy in IVF. Additionally, this HRG genotype may increase the risk in IVF of only developing embryos unfit for transfer.SHB is an adaptor protein involved in intracellular signaling complexes that regulate angiogenesis, the immune system and cell proliferation/apoptosis. Shb knockout mice have altered oocyte/follicle maturation and impaired embryogenesis. The impact of three SHB polymorphisms (rs2025439, rs13298451 and rs7873102) on human fertility is studied for the first time. The SNP prevalences did not differ between infertile and fertile women. BMI, gonadotropin dosages, the percentage of immature oocytes, the number of fertilized oocytes, the percentage of good-quality embryos and the day of embryo transfer seems to be affected by SHB genotype.In conclusion, HRG and SHB appear to influence female fertility. They are potential biomarkers that might be used for predicting pregnancy chance in infertile women. Knowledge of these genotypes may improve patient counseling and individualization of treatment.
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| 63. |
- Nordqvist, Sarah, 1962-, et al.
(författare)
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Histidine-Rich Glycoprotein Polymorphism and Pregnancy Outcome : a pilot study
- 2011
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Ingår i: Reproductive BioMedicine Online. - : Elsevier BV. - 1472-6483 .- 1472-6491. ; 23:2, s. 213-219
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Tidskriftsartikel (refereegranskat)abstract
- Histidine-rich glycoprotein (HRG) is involved in fibrinolysis and coagulation, the immune system and angiogenesis. These processes are all crucial in establishing and maintaining pregnancy. The primary aim of this pilot study was to determine if HRG affects pregnancy outcome. The secondary aim was to investigate if a specific genetic polymorphism (rs9898 C/T) in the HRG gene is associated with pregnancy results. The polymorphism leads to expression of either a serine or proline residue at position 186 in the protein sequence. In this study, women undergoing IVF were included. The genetic polymorphism in the HRG gene was analysed by Western blot and single nucleotide polymorphism analysis. None of the women homozygous for the serine at residue 186 became pregnant whereas the women homozygous for proline at residue 186 had higher than expected pregnancy rates. As far as is known,this is the first study to show that a specific genetic polymorphism in the HRG gene of a woman affects her chances of becoming pregnant after IVF. The results may be essential in improving advice and IVF treatment for couples with unexplained infertility.We have found a new test which might potentially improve advice and treatment for infertile couples considering IVF treatment. Histidine-rich glycoprotein (HRG) is involved in the system preventing blood clots or excess bleeding, the immune system and the system regulating blood vessel formation. Tight regulation of these processes is necessary for a pregnancy to be successful. This study examines how a specific genetic variant of HRG can affect pregnancy rates after IVF. The genetic polymorphism leads to expression of two different protein variations. One variation has a serine amino acid attached at position 186 and the other variation has a proline amino acid attached at the same position. Which variation a women produces is inherited co-dominantly. In this study, women undergoing IVF were included. To determine which variation each woman had, two different methods were used: Western blot and single nucleotide polymorphism analysis. The experimental results were then related to the woman’s medical records. None of the women who only produced the variation of HRG with a serine attached became pregnant, whereas the women who produced only the proline variation had higher than expected pregnancy rates. We show for the first time that the genetic background of a woman may affect her chances of becoming pregnant after IVF. The results might be essential in improving advice and IVF treatment for infertile couples.
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| 64. |
- Nordqvist, Sarah, 1962-, et al.
(författare)
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The Presence of Histidine-Rich Glycoprotein in the Female Reproductive Tract and in Embryos
- 2010
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Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7191 .- 1933-7205. ; 17:10, s. 941-947
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Tidskriftsartikel (refereegranskat)abstract
- A well-regulated angiogenesis is crucial for proper embryo implantation, embryogenesis, and pregnancy development. Monitoring the presence and distribution of angiogenic regulators in the female reproductive tract and in the early embryo is important for a broader understanding of the molecular aspects of fertility, embryogenesis, and pregnancy. Histidine-rich glycoprotein (HRG) is a glycoprotein involved in angiogenesis. Its presence in the female reproductive tract or in embryos has not previously been studied. Follicular fluid, culture medium, and embryos were obtained from patients undergoing in vitro fertilization (IVF). Biopsies from inner genitalia and placenta were collected at surgery. Histidine-rich glycoprotein presence was investigated by immunohistochemistry and Western blot. Polymerase chain reaction (PCR) was used to determine HRG expression in tissues or by embryos. We identified HRG in follicular fluid, the female reproductive tract, and placenta, as well as in the embryos. Moreover, HRG expression was observed in blastocysts. Thus, the angiogenic properties of HRG might affect fertility.
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| 65. |
- Parn, Triin, et al.
(författare)
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Physical activity, fatness, educational level and snuff consumption as determinants of semen quality : findings of the ActiART study
- 2015
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Ingår i: Reproductive BioMedicine Online. - : Elsevier BV. - 1472-6483 .- 1472-6491. ; 31:1, s. 108-119
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Tidskriftsartikel (refereegranskat)abstract
- In this study, the association between physical activity and other potential determinants, objectively measured by accelerometry, was examined. Sixty-two men attending an infertility clinic participated in the study. Obese men (body mass index >= 30) and those with a waist circumference 102 cm or more had lower semen volume than the other men (P < 0.05). Higher values in sperm parameters were observed in participants who completed university studies and those who did not consume snuff, compared with the other participants (P < 0.05). Finally, men who spent an average number of 10 min-bouts of moderate-to-vigorous physical activity had significantly better semen quality than those who engaged in low or high numbers of bouts of activity (P < 0.05). No associations were found for sedentary or moderate-to-vigorous physical activity time when it was not sustained over 10 min, i.e. not in bouts. Men who have average levels of physical activity over sustained periods of 10 min are likely to have better semen quality than men who engage in low or high levels of such activity. Similarly, high levels of total and central adiposity, low educational level and snuff consumption are negatively related to semen quality.
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| 66. |
- Rajareddy, Singareddy, 1977-
(författare)
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Studies of phosphatidylinositol 3 kinase (PI3K) signaling pathway in mammalian ovarian follicle activation and development
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The intra-oocyte signaling pathways that control oocyte growth and early follicular development are largely unknown. The aim of this thesis was to investigate the regulation and functions of phosphatidylinositol 3 kinase (PI3K) pathway in the oocyte, focusing in the roles of Foxo3a, p27, and Pten (phosphatase and tensin homolog deleted on chromosome ten). The physiological significance of Foxo3a in oocytes had been investigated by generating a transgenic mouse, whereby constitutively active Foxo3a is maintained in oocytes using the oocyte-specific ZP3 (Zona pellucida) promoter. The expression of the constantly active “negative” molecule Foxo3a in mouse oocytes was found to cause retardation of oocyte growth, resulting in a significant reduction in oocyte volume in secondary follicles. The transgenic mice also showed arrested follicular development and were infertile. In addition, when Foxo3a was overexpressed in oocytes of primary follicles, oocyte growth and follicular development were retarded. One of the causes of this phenotype may be the retained expression of the cyclin-dependent kinase (Cdk) inhibitor 1B (Cdkn1b), commonly known as p27kip1 or p27, in the nuclei of oocytes. The role and related mechanisms of p27 in controlling early follicular development and oocyte growth were then investigated using wild-type and p27-deficient (p27-/-) mice, and we demonstrated that (i) p27 suppresses follicle endowment/formation and activation, (ii) p27 induces follicle atresia that occurs prior to sexual maturity, and (iii) the overactivated follicles in p27-/- ovaries are depleted in early adulthood, causing premature ovarian failure (POF). In this thesis, we also provide genetic evidence that in mice with conditional deletion of Pten a major negative regulator of PI3K in oocytes, the entire pool of primordial follicles becomes activated, and subsequently all activated follicles are depleted in young adulthood, causing POF. Further mechanistic studies revealed that loss of Pten in oocytes resulted in elevated Akt signaling, which led to upregulation of both expression and activation of ribosomal protein S6 (rpS6) in oocytes. The results thus show that the mammalian oocyte serves as the headquarters of programming of the occurrence of follicle activation, and that the PI3K pathway of the oocyte governs follicle activation through control of initiation of oocyte growth.
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| 67. |
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| 68. |
- Ronquist, Göran K., et al.
(författare)
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Prostasomal DNA Characterization and Transfer Into Human Sperm
- 2011
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Ingår i: Molecular Reproduction and Development. - : Wiley. - 1040-452X .- 1098-2795. ; 78:7, s. 467-476
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Tidskriftsartikel (refereegranskat)abstract
- Human prostasomes, exosome-like microvesicles secreted by acinar cells of the prostate gland, contain chromosomal DNA. Agarose gel electrophoresis of DNA from seminal prostasomes displayed fragments of over 12 kb and smaller, with a distinct band around 1 kb that was excised, cloned, and sequenced. The sequences showed 8 out of 25 clones (32%) originating from genes. We elaborated the concept further by carrying out a genome-wide DNA copy number analysis of prostasomal DNA, hypothesizing that human prostasomes contain fragments of DNA randomly selected from the entire genome. Acridine orange-stained prostasomes were incubated with freshly prepared sperm for different times, and a transfer of acridine orange-stained prostasomal DNA to sperm (preferentially the head region) was observed. Fluorescence microscopy of slices in the center of 14 optical slides of the sperm head displayed an even fluorescence rather than a halo-like one, indicating DNA-uptake rather than just binding along the sperm head membrane.
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| 69. |
- Ronquist, Göran K, et al.
(författare)
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Prostasomes are heterogeneous regarding size and appearance but affiliated to one DNA-containing exosome family
- 2012
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Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 72:16, s. 1736-1745
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Prostate acinar epithelial cells release microvesicles (prostasomes) that possess pleiotropic biological effects relevant for successful fertilization. Prostasomes are formed in a similar way as exosomes but are heterogeneous as regards size and appearance. Like exosomes they are thought to be mediators of intercellular communication.METHODS:We prepared seminal prostasomes in accordance with the prevailing protocol for exosome preparation including passage through a 0.2 µm filter and centrifugation in a sucrose gradient.RESULTS:We compared the "filterable prostasomes" with those trapped on the filter ("nonfilterable prostasomes") and, qualitatively, no conspicuous differences were apparent regarding ultrastructure and SDS-PAGE banding pattern. Moreover, both types of prostasomes contained DNA fragments and Western blot revealed presence of prostate specific membrane antigen (PSMA), CD38, and annexin A1.CONCLUSIONS: Reasonably, prostasomes could be included in the exosome family and be regarded as one entity containing chromosomal DNA.
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| 70. |
- Ronquist, K Göran, et al.
(författare)
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Human prostasomes express glycolytic enzymes with capacity for ATP production
- 2013
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 304:6, s. E576-E582
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Tidskriftsartikel (refereegranskat)abstract
- Prostasomes are prostate-derived, exosome-like microvesicles that transmit signaling complexes between the acinar epithelial cells of the prostate and sperm cells. A vast majority of prostasomes has a diameter of 30 - 200 nm and they are generally surrounded by a classical membrane bilayer. Using a selected proteomic approach, it became increasingly clear that prostasomes harbor distinct subsets of proteins that may be linked to adenosine triphosphate (ATP) metabolic turnover that in turn might be of importance in the role of prostasomes as auxiliary instruments in the fertilization process. Among the 21 proteins identified most of the enzymes of anaerobic glycolysis were represented and three of the glycolytic enzymes present are among the ten top proteins found in most exosomes, once again linking prostasomes to the exosome family. Other prostasomal enzymes involved in ATP turnover were adenylate kinase, ATPase, 5'-nucleotidase and hexose transporters. The identified enzymes in their prostasomal context were operational for ATP formation when supplied with substrates. The net ATP production was low due to a high prostasomal ATPase activity that could be partially inhibited by vanadate that was utilized in order to profile the ATP forming ability of prostasomes. Glucose and fructose were equivalent as glycolytic substrates for prostasomal ATP formation and the enzymes involved were apparently surface-located on prostasomes, since an alternative substrate not being membrane-permeable (glyceraldehyde 3-phosphate) was operative, too. There is no clear cut function linked to this subset of prostasomal proteins but some possible roles are discussed.
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