Distributions of high-density lipoprotein particle components in human follicular fluid and sera and their associations with embryo morphology parameters during IVF

Department of Biotechnical and Clinical Laboratory Sciences, University at Buffalo, State University of New York, 26 Cary Hall, 3435 Main Street, Buffalo, NY 14214, USA.
Human Reproduction (Impact Factor: 4.57). 08/2008; 23(8):1884-94. DOI: 10.1093/humrep/den183
Source: PubMed


High-density lipoprotein (HDL) is the sole lipoprotein present in follicular fluid (FF). The objectives of this study were to examine HDL lipid composition and associated enzyme activities in FF and serum and to relate these levels to embryo morphology parameters in women undergoing in vitro fertilization (IVF).
Serum and FF were prospectively obtained from 60 women undergoing IVF. HDL lipids, apolipoprotein AI (ApoAI), paraoxonase 1 (PON1) and paraoxonase 3 (PON3) activities were determined. Bivariate analysis and ordinal logistic regression models were employed to examine the associations between biochemical measures and embryo morphology parameters [embryo cell number (ECN) and embryo fragmentation score (EFS)] as surrogate markers of oocyte health.
All biochemical parameters were significantly (P < 0.05) lower in FF than serum except PON3 levels which were significantly higher. FF-HDL cholesterol (OR 0.66, 95%CI 0.46-0.96) and ApoAI (OR 0.13, 95%CI 0.03-0.97) levels were negative predictors for EFS; however, their effects were not independent and the level of one moderated the effect of the other. Limited to Day 3 embryo transfers, FF-PON1-arylesterase activity was a significant positive predictor for ECN (OR 1.09, 95%CI 1.01-1.17).
In this pilot study, our data suggests that HDL and its component proteins within FF may play protective roles in the health of the human oocyte and subsequent early embryo development. We describe for the first time the activities of PON1 and PON3 in FF. We suspect that PON3 activity may be locally generated due to higher activities in FF compared with serum.

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Available from: Michael S Bloom, Oct 04, 2015
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    • "lay a role in fertility . In fact , some SNPs are related to altered FF progesterone levels and a reduction in the number of ongoing pregnancies ( Yates et al . 2011 ) . Finally , studies on FF collected during ovum pick up in an IVF treatment show that concentrations of HDL and its lipoprotein apoA1 are inversely related to embryo fragmentation ( Browne et al . 2008 ) , but also to embryo cleavage , blastocyst formation and embryo quality ( Valckx et al . 2012 , Wallace et al . 2012 ) , resulting in a reduced implantation potential ."
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    ABSTRACT: The relationship among maternal lipid metabolism, fetal development, and adult disease of the offspring represents an emerging topic of high epidemiological relevance. The present review highlights the very early aspects of this process. Recent data suggest a link between lipid metabolism and reproduction/fertility, not only on the systemic level, but also locally on the level of the ovary that maintains its own sterol metabolism, likely in a self-regulated fashion. Follicular fluid–which surrounds oocytes in a developing follicle–contains all relevant lipoprotein subclasses that reach the follicular fluid either by diffusion, in the case of high-density lipoproteins (HDL), or by local production within the granulosa cells, in the case of very low-density lipoproteins (VLDL). Here, we summarize current knowledge on lipoprotein metabolism in the ovary in the context of fertility, and hypothesize that lipoproteins within follicular fluid are relevant to the development of the early embryo and thereby putatively also to the programming of metabolic disease later in life.
    Journal of Reproductive Immunology 10/2014; 104-105(1). DOI:10.1016/j.jri.2014.04.003 · 2.82 Impact Factor
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    • "To interpret possible specific differences between plasma and FF, the transfer of these components from plasma across the blood–follicle barrier to the follicle should be taken into account. It has been demonstrated that, among lipoproteins, very-low density and low-density lipoproteins are mostly excluded from the transfer and that high-density lipoproteins are predominant in FF (Browne et al., 2008); consequently, only carotenoids and a-tocopherol associated with the high-density lipoproteins fraction are recovered from FF (Schweigert et al., 2003). The intrafollicular concentrations of some of the investigated components may also be affected by other means, such as local conversion of carotenoids with provitamin A activity (b-carotene) into vitamin A (retinol) or other selective metabolic mechanisms within the follicle itself. "
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    ABSTRACT: Ovarian stimulation is used with IVF/intracytoplasmic sperm injection (ICSI) cycles to obtain multiple oocytes and improve pregnancy rates; however, it also induces perturbation in the oxidant–antioxidant balance leading to oxidation stress. The present study monitored the plasma antioxidant status in women undergoing a long agonist protocol of ovarian stimulation at three different time points: at baseline (T0), after pituitary suppression (T1) and on the day of oocyte retrieval (T2). The antioxidant composition of follicular fluid samples collected on T2 was also evaluated. Significant decreases (P < 0.05) of plasma vitamin C, vitamin E and carotenoids were found between T1 and T2 but not between T0 and T1. At T2, high plasma vitamin E was associated with high numbers of total and mature oocytes retrieved per patient, which, in turn, were favourable for achieving pregnancy. Accordingly, women who became pregnant presented higher vitamin E concentrations both in plasma and FF than those who did not. In conclusion, this study confirmed the occurrence of significant modifications of the plasma antioxidant profile during ovarian stimulation with gonadotrophins; at the same time, it was found that both systemic and follicular antioxidant status may be related to IVF/ICSI outcome.
    Reproductive biomedicine online 07/2014; 29(1). DOI:10.1016/j.rbmo.2014.03.010 · 3.02 Impact Factor
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    • "Paraoxonase (PON) is one of the strong antioxidants in the serum and the follicular fluid (FF). PON1 and PON3, which are both associated in serum with high density lipoprotein (HDL) cholesterol (C), protect the serum lipids from oxidation, probably through their ability to hydrolyze specific oxidized lipids (7, 8). The PON gene family consists of three members of PON1 gene, PON2 gene and PON3 gene, encoding PON enzyme family (4). "
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    ABSTRACT: Paraoxonase-3 (PON3), as a high density lipoprotein (HDL)-associated lactonase, is capable of preventing the oxidative modification of low density lipoprotein (LDL). PON3 activity in follicular fluid (FF) is three times more than its activity in serum. However, the detailed role of PON3 in women's fertility remains unknown. The aim of this study was to investigate the correlation between PON3 activity in the FF of women undergoing assisted reproductive technique (ART), in vitro fertilization (IVF), or intra-cytoplasmic sperm injection (ICSI). This cross-sectional study consisted of 50 women from couples with male factor infertility (MFI) or with female factor infertility (FFI). The FF samples were obtained during the ART intervention. PON3 activity, HDL cholesterol (HDL C), total antioxidant status (TAS) and the level of malondialdehyde (MDA) were determined. The morphology of the embryo was determined using embryo cell number (ECN) and embryo fragmentation score (EFS). In addition, fertilization rate (FR) was used an oocyte fertilization index. Of 50 women, 20 women belonged to FFI group and the remaining 30 women belonged to MFI group. PON3 activity in FF of women in FFI group was significantly lower (p<0.05) in comparison with corresponding value in MFI group. The value of PON3 activity/MDA in the FFI group was lower than that in MFI group. Moreover, MDA level in the FF of FFI group was significantly higher (p<0.05) than its concentration in MFI group. Meanwhile, no significant difference was found in HDL-C concentration and TAS of both groups. No significant correlation was observed between the ECN and FF biochemical parameters. There was also a negative correlation between FR and MDA (r=-0.42, p=0.02), whereas a positive relation between FR with PON3 activity (r=0.59, p=0.004), HDL-C (r=0.35, p=0.04) and PON3/MDA (r=0.59, p=0.001). According to the results of this study, PON3 activity level as a key component of antioxidant system in FF may directly be associated with the success rate of ART and fertilization rate in women.
    International journal of fertility & sterility 04/2014; 8(1):51-8. · 0.47 Impact Factor
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