Phytoestrogens, polyphenolic compounds derived from plants, are more and more common constituents of human and animal diets. In most of the cases, these chemicals are much less potent than endogenous estrogens but exert their biological effects via similar mechanisms of action. The most common source of phytoestrogen exposure to humans as well as ruminants is soybean-derived foods that are rich in the isoflavones genistein and daidzein being metabolized in the digestive tract to even more potent metabolites—para-ethyl-phenol and equol. Phytoestrogens have recently come into considerable interest due to the increasing information on their adverse effects in human and animal reproduction, increasing the number of people substituting animal proteins with plant-derived proteins. Finally, the soybean becomes the main source of protein in animal fodder because of an absolute prohibition of bone meal use for animal feeding in 1995 in Europe. The review describes how exposure of soybean-derived phytoestrogens can have adverse effects on reproductive performance in female adults.
BackgroundIn the cow, lysophosphatidic acid (LPA) acts as an auto-/paracrine factor, through its receptors LPAR1-4, on oocytes and cumulus cells during in vitro maturation (IVM). The aim of the present work was to determine the effect of LPA during IVM of bovine oocytes on: 1) oocyte maturation; 2) apoptosis of COCs; 3) expression of genes involved in developmental competence and apoptosis in bovine oocytes and subsequent blastocysts; 4) cumulus expansion and expression of genes involved in the ovulatory cascade in cumulus cells; 5) glucose metabolism and expression of genes involved in glucose utilization in cumulus cells; 6) cleavage and blastocyst rates on Day 2 and Day 7 of in vitro culture, respectively.MethodsCumulus-oocyte complexes (COCs) were matured in vitro in the presence or absence of LPA (10−5M) for 24h. Following maturation, we determined: oocyte maturation stage, cumulus expansion, COCs apoptosis and glucose and lactate levels in the maturation medium. Moreover, COCs were either used for gene expression analysis or fertilized in vitro. The embryos were cultured until Day 7 to assess cleavage and blastocyst rates. Oocytes, cumulus cells and blastocysts were used for gene expression analysis.ResultsSupplementation of the maturation medium with LPA enhanced oocyte maturation rates and stimulated the expression of developmental competence-related factors (OCT4, SOX2, IGF2R) in oocytes and subsequent blastocysts. Moreover, LPA reduced the occurrence of apoptosis in COCs and promoted an antiapoptotic balance in the transcription of genes involved in apoptosis (BAX and BCL2) either in oocytes or blastocysts. LPA increased glucose uptake by COCs via augmentation of GLUT1 expression in cumulus cells as well as stimulating lactate production via the enhancement of PFKP expression in cumulus cells. LPA did not affect cumulus expansion as visually assessed, however, it stimulated upstream genes of cumulus expansion cascade, AREG and EREG.ConclusionsSupplementation of the maturation medium with LPA improves oocyte maturation rates, decreases extent of apoptosis in COCs and sustains the expression of developmental competence related factors during oocyte maturation and subsequently affects gene expression profile at the blastocyst stage. We also demonstrate that LPA directs glucose metabolism toward the glycolytic pathway during IVM.
Abstract. We examined whether the CL is a site for lysophosphatidic acid (LPA) synthesis and/or a target for LPA action in the bovine reproductive tract. LPA concentrations in the CL tissue increased towards the end of the cycle and were stable during early pregnancy. No changes in the expression of LPA receptors (LPARs) occurred during the estrous cycle. The expressions of LPAR2 and LPAR4 on days 17-19 of pregnancy were higher than those on the respective days of the estrous cycle and higher than those on days 8-10 of pregnancy. LPA stimulated P4 synthesis via 3βHSD stimulation but did not modulate the interferon-tau (IFNτ) influence on P4 synthesis in steroidogenic cells. Moreover, we found LPA-dependent stimulation of IFNτ action on 2,5'-oligoadenylate synthase (OAS1) and ubiquitin-like IFN-stimulated gene 15-kDa protein (ISG15) expression. The present study demonstrated that the CL might be a site of LPA synthesis and target of LPA action in the bovine reproductive tract. We postulate that during the estrous cycle and early pregnancy, LPA exerts autocrine and paracrine effects on the CL mainly via LPAR2 and LPAR4. The stimulatory effect of LPA on P4 synthesis via 3βHSD stimulation and LPA-dependent stimulation of IFNτ action on OAS1 and ISG15 expression suggest that LPA is an additional auxiliary luteosupportive factor in steroidogenic cells. T he corpus luteum (CL) is an endocrine gland that is temporarily formed in the ovary and undergoes regression at the end of the estrous cycle [1]. After ovulation, it forms from the Graafian follicle, grows and vascularizes rapidly. The bovine CL consists of a variety of cell types including large and small luteal cells, endothelial cells, fibroblasts and immune cells [2,3]. In nonpregnant cows, the CL undergoes luteolysis and becomes nonfunctional around days 17-18 after ovulation [4,5]. The main function of the CL both during the cycle and pregnancy is synthesis of progesterone (P4), which plays major roles in the regulation of the length of the estrous cycle and in the implantation of the blastocyst after fertilization [6]. During maternal recognition of pregnancy, the conceptus synthesizes and secretes interferon tau (IFNτ), which protects the CL and extends the estrous cycle [7]. In addition to its antiluteolytic effects, IFNτ increases expression of several IFN-stimulated genes (ISG), such as 2',5'-oligoadenylate synthetase (OAS1) and ubiquitin-like IFNstimulated gene 15-kDa protein (ISG15) in the uterus [8], mammary gland and CL [9] in cattle. However, during maternal recognition of pregnancy, P4 is the main factor responsible for its successful establishment. Luteinizing hormone (LH) is the most important regulator of P4 synthesis [10,11]. The growth and development of the early CL is supported by many factors, including LH, PGs (PGE 2 and PGI 2 ), oxytocin, noradrenaline and growth factors [12][13][14][15]. The CL can also autoregulate the synthesis of P4 [16].Lysophosphatidic acid (LPA) has been shown to affect the reproductive processes in rats [17], pigs [1...
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