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Primordial germ cells develop into oocytes and sperm cells. These cells are useful resources in reproductive biology and regenerative medicine. The mesenchymal stem cells (MSCs) have been examined for in vitro production of primordial germ cell-like cells (PGLCs). This study aimed to summarize the existing protocols for MSCs differentiation into PGLCs. In limited identified studies, various models of MSCs, including those derived from adipose tissue, bone marrow, and Wharton's jelly, have been successfully differentiated in to PGLCs. Although the protocols of specification induction are basically very similar, they have been adjusted to the mesenchymal cell type and the species of origin. The availability of MSCs has made it possible to customize conditions for their differentiation into PGLCs in several models, including humans. Refining germ cell-related signaling pathways during induced differentiation of MSCs will help to define extension to the protocols for PGLCs production. [ABSTRACT FROM AUTHOR]

Infertility is a growing problem worldwide. Currently, in vitro fertilization (IVF) is widely performed to treat infertility. However, a high percentage of IVF cycles fails, due to the poor developmental potential of the retrieved oocyte to generate viable embryos. Fatty acid content of the follicular microenvironment can affect oocyte maturation and the subsequent developmental competence. Saturated and monounsaturated fatty acids are mainly used by follicle components as primary energy sources whereas polyunsaturated fatty acids (PUFAs) play a wide range of roles. A large body of evidence supports the beneficial effects of n‐3 PUFAs in prevention, treatment, and amelioration of some pathophysiological conditions including heart diseases, cancer, diabetes, and psychological disorders. Nevertheless, current findings regarding the effects of n‐3 PUFAs on reproductive outcomes in general and on oocyte quality more specifically are inconsistent. This review attempts to provide a comprehensive overview of potential molecular mechanisms by which n‐3 PUFAs affect oocyte maturation and developmental competence, particularly in the setting of IVF and thereby aims to elucidate the reasons behind current discrepancies around this topic. There is a large body of evidence showing that n‐3 polyunsaturated fatty acids (PUFAs) have benefits on general health. This review discusses molecular mechanisms by which n‐3 PUFAs affect oocyte maturation and developmental competence. [ABSTRACT FROM AUTHOR]

Potential reproductive effects are considered as the major aspect of biomolecules functionality in an organism. The recent identification of differential patterns of fatty acids across ovarian follicles and their association with levels of sexual maturity highlights the importance of these biomolecules. It is well known that fatty acids are highly diverse in terms of their functional properties. Oleic acid is chemically classified as an unsaturated omega-9 fatty acid. Besides serving as an important energy source, oleic acid is involved in metabolic and structural roles. Free and esterified oleic acids are compartmentalized into discrete extracellular fluids, cell organelles and found within the cytosol. This review summarizes the current knowledge on the contribution of oleic acid in regulating female fertility, particularly its involvement in female germ cell growth and development. Oleic acid has been identified as a blastomeric and post-cryopreservation survival biomarker in bovine. Several related studies have shown the critical role of oleic acid in counteracting the detrimental effects of saturated fatty acids and in paracrine support of oocyte development. Although available data are not ideally detailed, most data suggest that oleic acid can contribute to normal oocyte and preimplantation embryo development via mechanisms involving metabolic partitioning of fatty acids, change in the membrane structural organization, attenuation of oxidative stress and regulation of intracellular signalling. Thus, oleic acid may play a significant role in oocyte and early embryo development, suggesting that future studies should explore in more detail its potential effects on the physiopathology of female reproduction. [ABSTRACT FROM AUTHOR]

Background: The omega-3 fatty acid (ω-3 fatty acid) such as eicosapentaenoic acid (EPA) is currently used in the clinic as a nutritional supplement in the treatment of polycystic ovarian syndrome (PCOS). The present study was designed to investigate the effect of EPA on the expression levels of peroxisome proliferator-activated receptor gamma (PPARγ) and cytochrome P450 aromatase (encoded by the CYP-19) in primary cultured granulosa cells (GC) from patients undergoing in vitro fertilization (IVF), and also to compare these effects with those in GC of PCOS patients. Materials and Methods: In this experimental study, human GC were isolated, primary cultured in vitro, exposed to a range of concentrations of the EPA and investigated with respect to gene expression levels of PPARγ and CYP-19 using real time-polymerase chain reaction (PCR). The participants (n=30) were the patients admitted to the IVF Center in February-March 2013 at Alzahra Hospital, Tabriz, Iran, who were divided into two groups as PCOS (n=15) and non-PCOS (n=15) women (controls). Results: All doses of the EPA significantly induced PPARγ mRNA gene expression level as compared to the control recombinant follicle stimulating hormone (rFSH) alone condition. High doses of EPA in the presence of rFSH produced a stimulatory effect on expression level of PPARγ (2.15-fold, P=0.001) and a suppressive effect (0.56-fold, P=0.01) on the expression level of CYP-19, only in the PCOS GC. Conclusion: EPA and FSH signaling pathway affect differentially on the gene expression levels of PPARγ and CYP-19 in PCOS GC. Altered FSH-induced PPARγ activity in PCOS GC may modulate the CYP-19 gene expression in response to EPA, and possibly modulates the subsequent steroidogenesis of these cells. [ABSTRACT FROM AUTHOR]

Background: 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). Materials and Methods: 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. Results: 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). Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: The omega-3 (ω-3) fatty acid eicosapentaenoic acid (EPA) is currently used in the clinic as a nutritional supplement to improve infertility, particularly in women with polycystic ovarian syndrome (PCOS). Objective: The present study was designed to investigate the effect of EPA on insulin-like growth factor 1 (IGF-1) and cyclooxygenase 2 (COX-2) gene expression in primary cultured granulosa cells from patients undergoing in vitro fertilization (IVF), and also to compare this effect with those in granulosa cells of PCOS patients. Materials and Methods: In this experimental study, human granulosa cells were isolated from follicular fluid of normal and PCOS women undergoing IVF by hyaluronidase digestions, followed by Percoll gradient centrifugation. Cells were cultured in vitro, exposed to a range of concentrations of the EPA (25-100 μM) for 24 hr, and investigated with respect to COX-2 and IGF-1 gene expression by real time-PCR. Results: In both groups, all doses of the EPA significantly induced IGF-1 mRNA gene expression compared to the untreated control. High doses of EPA in the presence of recombinant (r) FSH produced a stimulatory effect on IGF-1 and a suppressive effect (p=0.01) on the COX-2 gene expression, which were more pronounced in granulosa cells from PCOS patients. Conclusion: EPA affect diversely the gene expression of IGF-1 and COX-2 in granulosa cells, which were more pronounced in PCOS compared to control. These findings represent the possible underlying molecular mechanisms for the positive impact of the ω-3 fatty acids on reproduction, especially in patients with PCOS. [ABSTRACT FROM AUTHOR]

The Δ6-desaturase (Δ6D), also known as fatty acid desaturase 2, is a regulatory enzyme in de novo fatty acid synthesis, which has been linked to obesity and diabetes. The aim of the present study was to investigate the effect of peroxisome proliferative-activated receptor δ (PPAR δ ) agonist and MEK/ERK1/2-dependent pathway on the expression of Δ6D in human pancreatic carcinoma cell line PANC-1. PANC-1 cells cultured in RPMI-1640 were exposed to the commonly used ERK1/2 pathway inhibitor PD98059 and PPAR δ agonist GW0742. Changes in mRNA and protein expression of Δ6D were then determined using real-time RT-PCR and Western blot, respectively. The expression of Δ6D (P < 0.01) increased following treatment with PPAR δ agonist both at mRNA and protein levels, whereas no significant change was observed after treatment with MEK/ERK1/2 pathway inhibitor. It was also found that the increase in the expression of Δ6D in response to GW0742 was significantly inhibited by PD98059 (>40%, P < 0.05) or EGF receptor-selective inhibitor AG1478 (>25%, P < 0.05) pretreatment. PPAR δ and MEK/ERK1/2 signaling pathways affect differentially the expression of Δ6D in pancreatic cancer cells. Furthermore, there may be an inhibitory crosstalk between these two regulatory pathways on the mRNA expression of Δ6D and subsequently on Δ6D protein expression.