Sea buckthorn, its bioactive constituents, and mechanism of action: potential application in female reproduction.

Sea buckthorn (Hippophae rhamnoides L.) is a flowering shrub, and its berries have been utilized for decades as a raw ingredient in cuisines and herbal remedies. This evidence-based study focuses on its key bioactive constituents, and mechanism of protective effects with a focus on female reproductive processes. Parts of the plant contain phenols, carotenoids (lycopene, carotene, lutein, and zeaxanthin), flavonoids (isorhamnetin, quercetin, glycosides, and kaempferol), tocopherols, sterols, polyunsaturated fatty acids, minerals, vitamins, omega 3, 6, 9 and rare omega 7 fatty acids etc. Key polyphenolic flavonoids such as isorhamnetin and quercetin are believed to be mainly responsible behind its health benefits (against cardiovascular diseases, metabolic syndrome, obesity etc.) through properties including anti-cancer, antioxidant, and anti-inflammatory activities. These sea buckthorn constituents appear to mediate healthy ovarian cell proliferation, death, and hormone release, as well as decrease ovarian cancer possibly through apoptosis, and hormonal (estrogen) release. Thus, sea buckthorn and its bioactive ingredients may have potential in the management of gynecological problems such as uterine inflammation, endometriosis, and easing symptoms of vulvovaginal atrophy in postmenopausal women (by targeting inflammatory cytokines and vascular endothelial growth factor - VEGF). Apigenin, myricetin, and luteolin have also been recommended as prospective ovarian cancer preventative and adjuvant therapy options as they can inhibit ovarian cancerogenesis by triggering apoptosis and halting the cell cycle in ovarian tumors. Furthermore, its oil (containing carotenoid, sterol, and hypericin) has been speculated as an alternative to estrogen replacement therapy for postmenopausal women particularly to improve vaginal epithelial integrity. However, it is uncertain whether steroid hormone receptors, reactive oxygen species (ROS), and inflammatory regulators are actually behind sea buckhorn's actions. Sea buckthorn, and its compounds' health promoting potential warrants further validation not just in vitro and in animal research, but also in clinical trials to identify and/or standardize optimal methods of delivery of biologically active molecules.

Modulatory effect of pomegranate peel extract on key regulators of ovarian cellular processes in vitro.

In this study, response of ovarian cells (human granulosa cell line HGL5, and human adenocarcinoma cell line OVCAR-3) to short-term pomegranate peel extract (PPE) treatment (for 24 hours in cell culture) was evaluated in vitro. Quantitative and qualitative screening of polyphenols revealed punicalagins α and ß as major polyphenolic components. Total phenolic content (TPC) was 93.76 mg GAE/g d.w. with a high antioxidant activity of 95.30 mg TEAC/g d.w. In OVCAR-3, PPE treatment inhibited the metabolic activity, and increased cyclin-dependent kinase 1 (CDKN1A, p21) level at the highest dose, but not in HGL5. Flow cytometry analysis could not detect any significant difference between proportions of live, dead, and apoptotic cells in both cell lines. Reactive oxygen species (ROS) revealed an antioxidant effect on HGL5, and a prooxidant effect by stimulating ROS generation in OVCAR-3 cells at the higher doses of PPE. However, in contrast to HGL5, PPE treatment decreased release of growth factors - TGF-ß2 and EGF at the highest dose, as well as their receptors TGFBR2 and EGFR in OVCAR-3 cells. PPE also influenced steroidogenesis in granulosa cells HGL5 by stimulating 17ß-estradiol secretion at higher doses. In conclusion, the present study highlighted the bioactive compounds in pomegranate peels and the possible mechanisms of action of PPE, shedding light on its promising role in ovarian cancer (chemo)prevention and/or management.

Reactive oxygen species mediated apoptotic death of colon cancer cells: therapeutic potential of plant derived alkaloids.

Colorectal cancer (CRC) is one of the most deaths causing diseases worldwide. Several risk factors including hormones like insulin and insulin like growth factors (e.g., IGF-1) have been considered responsible for growth and progression of colon cancer. Though there is a huge advancement in the available screening as well as treatment techniques for CRC. There is no significant decrease in the mortality of cancer patients. Moreover, the current treatment approaches for CRC are associated with serious challenges like drug resistance and cancer re-growth. Given the severity of the disease, there is an urgent need for novel therapeutic agents with ideal characteristics. Several pieces of evidence suggested that natural products, specifically medicinal plants, and derived phytochemicals may serve as potential sources for novel drug discovery for various diseases including cancer. On the other hand, cancer cells like colon cancer require a high basal level of reactive oxygen species (ROS) to maintain its own cellular functions. However, excess production of intracellular ROS leads to cancer cell death via disturbing cellular redox homeostasis. Therefore, medicinal plants and derived phytocompounds that can enhance the intracellular ROS and induce apoptotic cell death in cancer cells via modulating various molecular targets including IGF-1 could be potential therapeutic agents. Alkaloids form a major class of such phytoconstituents that can play a key role in cancer prevention. Moreover, several preclinical and clinical studies have also evidenced that these compounds show potent anti-colon cancer effects and exhibit negligible toxicity towards the normal cells. Hence, the present evidence-based study aimed to provide an update on various alkaloids that have been reported to induce ROS-mediated apoptosis in colon cancer cells via targeting various cellular components including hormones and growth factors, which play a role in metastasis, angiogenesis, proliferation, and invasion. This study also provides an individual account on each such alkaloid that underwent clinical trials either alone or in combination with other clinical drugs. In addition, various classes of phytochemicals that induce ROS-mediated cell death in different kinds of cancers including colon cancer are discussed.

The multiple actions of grape and its polyphenols on female reproductive processes with an emphasis on cell signalling.

Grapes are an economically important fruit crop, and their polyphenols (mainly phenolic acids, flavanols, flavonols, anthocyanins, proanthocyanidins, and stilbenes) can exert a wide range of health benefits as an interesting and valuable dietary supplement for natural complementary therapy. However, their potential physiological and therapeutic actions on reproductive processes have not been sufficiently elucidated. This evidence-based study presents current knowledge of grape extracts and polyphenols, as well as their properties and therapeutical actions in relation to female reproduction in a nutshell. Grape extract, and its polyphenols such as resveratrol, proanthocyanidin B2 or delphinidin may influence female reproductive physiology and pathology, as well as regulate multiple signaling pathways related to reproductive hormones, steroid hormones receptors, intracellular regulators of oxidative stress and subsequent inflammation, apoptosis, and proliferation. Their role in the management of ovarian cancer, age-related reproductive insufficiency, ovarian ischemia, PCOS, or menopausal syndrome has been indicated. In particular, the potential involvement of grapeseed extracts and/or proanthocyanidin B2 and delphinidin on ovarian steroidogenesis, oocyte maturation, and developmental capacity has been implicated, albeit at different regulatory levels. Grape polyphenols exert a wide range of health benefits posing grape extract as an interesting and valuable dietary supplement for natural complementary therapy. This evidence-based study focuses on the actions of grapeseed extract and grape polyphenols on female reproductive processes at various regulatory levels and multiple signalling pathways by regulating reproductive hormones (GnRH, gonadotropins, prolactin, steroid hormones, IGFBP), steroid receptors, markers of proliferation and apoptosis. However, lack of knowledge of standardized dosages so far limits their clinical application despite the wide range of their biological and therapeutic potentials.

Polycystic Ovary Syndrome: An Updated Overview Foregrounding Impacts of Ethnicities and Geographic Variations.

Polycystic ovary syndrome (PCOS) is one of the most common heterogeneous conditions of the endocrine reproductive system in women of childbearing age. Hyperandrogenism and oligomenorrhea are the two core characteristics of PCOS, a complicated and multifaceted illness. The condition is also linked to several major side effects, which include type 2 diabetes, early atherosclerosis, infertility, and endometrial cancer. There are few facts and statistics available on PCOS prevalence internationally due to the significant degree of geographic and ethnic variance and inconsistency caused by different diagnosis standards. Limited (n = 179) explorations have been made in the context of the prevalence of this complicated illness so far, and out of these, only 55 studies have discussed its association with race and/or ethnicity. However, those studies remain restricted due to the small sample size, biased selection, and the lack of comparative studies. Variations in PCOS prevalence frequency also arise due to different diagnostic criteria, as well as racial and ethnic differences, associated lifestyle factors, and subsequent illnesses that affect the accuracy of the diagnosis. The main objective behind this systematic review is to provide comprehensive epidemiological data on PCOS that is organized geographically. This evidence-based study also provides an overview of the clinical management of PCOS to instigate further research on this complex endocrinological condition and the subsequent development of preventive treatment strategies.

Clinical Potential of Himalayan Herb Bergenia ligulata: An Evidence-Based Study.

Herbal products have been used in traditional systems of medicine and by ethnic healers for ages to treat various diseases. Currently, it is estimated that about 80% of people worldwide use herbal traditional medicines against various ailments, partly due to easy accessibility and low cost, and the lower side effects they pose. Bergenia ligulata, a herb ranging from the Himalayas to the foothills, including the north-eastern states of India, has traditionally been used as a remedy against various diseases, most prominently kidney stones. The medicinal properties of B. ligulata have been attributed to bergenin, its most potent bioactive component. Apart from bergenin, the other compounds available in B. ligulata are arbutin, gallic acid, protocatechuic acid, chlorogenic acid, syringic acid, catechin, ferulic acid, afzelechin, paashaanolactone, caryophyllene, 1,8-cineole, ß-eudesmol, stigmasterol, ß-sitosterol, parasorbic acid, 3-methyl-2-buten-1-ol, phytol, terpinen-4-ol, tannic acid, isovalaric acid, avicularin, quercetin, reynoutrin, and sitoinoside I. This review summarizes various medicinal properties of the herb, along with providing deep insight into its bioactive molecules and their potential roles in the amelioration of human ailments. Additionally, the possible mechanism(s) of action of the herb's anti-urolithiatic, antioxidative, antipyretic, anti-diabetic, anti-inflammatory and hepatoprotective properties are discussed. This comprehensive documentation will help researchers to better understand the medicinal uses of the herb. Further studies on B. ligulata can lead to the discovery of new drug(s) and therapeutics for various ailments.

COVID-19, Oxidative Stress and Male Reproduction: Possible Role of Antioxidants.

Coronavirus disease 2019 (COVID-19) involves a complex pathogenesis and with the evolving novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the long-term impacts of the unceasing COVID-19 pandemic are mostly uncertain. Evidence indicates deleterious impact of this disease upon male reproductive health. It is concerning that COVID-19 may contribute to the already global declining trend of male fertility. The adverse impacts of COVID-19 on male reproduction may primarily be attributed to the induction of systemic inflammatory responses and oxidative stress (OS), which operate as a vicious loop. Bringing the systemic inflammation to a halt is critical for 'putting out' the 'cytokine storm' induced by excessive reactive oxygen species (ROS) generation. The possibility of OS playing a prime role in COVID-19-mediated male reproductive dysfunctions has led to the advocacy of antioxidant therapy. An array of antioxidant defense medications has shown to be effective in experimental and clinical studies of COVID-19. The present review thus discusses the possibilities as to whether antioxidant drugs would contribute to combating the SARS-CoV-2 infection-induced male reproductive disruptions, thereby aiming at kindling research ideas that are needed for identification and treatment of COVID-19-mediated male reproductive impairments.

Black Elder and Its Constituents: Molecular Mechanisms of Action Associated with Female Reproduction.

The present review summarizes the current knowledge concerning provenance, properties, physiological and therapeutic actions of elderberry and the bioactive molecules present in the plant, with emphasis on their action on female reproduction. Elderberry or black elder (Sambucus nigra L.) attracts attention due to its easy cultivation and high availability of bioactive compounds. Most of the available data concerning black elder's therapeutic action are focused on its effects such as activation of immune processes and anti-inflammatory processes (cytokine production, etc.) and regulation of hormones and their receptors in cancer cells. The effects of elderberry on reproduction have been poorly investigated so far. Nevertheless, conducted studies so far demonstrate the stimulatory influence of black elder extract and its constituents, such as rutin, anthocyanins and agglutinins, on the viability and steroidogenesis of healthy ovarian cells as well as their ability to promote apoptosis and reduce the viability and proliferation of ovarian cancer cells. Furthermore, the action of black elder extract and its constituent biomolecules, such as anthocyanins and lectins, on embryogenesis and the embryonal estradiol-estradiol receptor system have also been reported. The available information, despite limitations, suggest the applicability of black elder constituents for improvement of reproductive processes in animal biotechnology, animal production and assisted reproduction, as well as for prevention and treatment of reproductive disorders (including cancer) in veterinary and human medicine.

Phytonutrients of Bitter Apricot Seeds Modulate Human Lipid Profile and LDL Subfractions in Adults with Elevated Cholesterol Levels.

The objective of the present study was to evaluate the effect of short-term consumption of bitter apricot seeds phytonutrients on cardiovascular risk factors with a special focus on LDL cholesterol subfractions using the Lipoprint system. A group of 34 adult volunteers (21 female/13 male) consumed 60 mg kg-1 of body weight of bitter apricot seeds daily for 42 days. Subjects were divided into two groups: one with normal cholesterol levels (NTC) and one with elevated total cholesterol levels (ETC). Blood serum levels of total cholesterol (T-C), low-density cholesterol (LDL-C), high-density cholesterol (HDL-C), and triglycerides (TG) did not change significantly (p > 0.05) in NTC group. However, there were significant decreasing of T-C (p ˂ 0.05) and LDL-C (p < 0.01) in ETC group. The LDL1, LDL2, and atherogenic LDL3-7 subfractions progressively decreased after 42 days of apricot seeds consumption in ETC group (p < 0.05). Apricot seeds consumption was associated with a significant increase in the mean LDL particle size especially in ETC group (p ˂ 0.01). The results of the present study support the hypothesis that daily consumption of bitter apricot seeds for 42 days positively modified the lipoprotein profile in the group with elevated total cholesterol.

Comparative analysis of the detrimental in vitro effects of three fusariotoxins on the selected structural and functional characteristics of rabbit spermatozoa.

In this study, we evaluated the in vitro effects of 1-50 µM zearalenone (ZEA), deoxynivalenol (DON) and T-2 toxin (T-2) on rabbit spermatozoa for as much as 8 h of in vitro exposure. Our results indicate that all sperm quality parameters were negatively affected by these fusariotoxins in a time- and dose-dependent manner. The most prominent structure affected by ZEA was the plasma membrane, exhibiting alterations consistent with the onset of apoptosis and reactive oxygen species (ROS) overproduction. This correlated with the most prominent decline of the sperm motility among all selected fusariotoxins. Significant necrotic changes and mitochondrial dysfunction were primarily responsible for the sperm damage in the presence of T-2. Finally, exposure of spermatozoa to DON led to a significant decrease in the DNA integrity. This study may provide new information on the specific mechanisms of action involved in the in vitro toxic behavior of fusariotoxins on male gametes.

Effect of Streptococcus uberis on Gamma Delta T Cell Phenotype in Bovine Mammary Gland.

In this study, we focused analyzing γδ T cells during bovine mammary gland inflammation induced by Streptococcus uberis. A mammary gland cell suspension was obtained using lavage 24, 48, 72, and 168 h after intramammary-induced infection. The proportion of lymphocytes increased during the entire week in which inflammation was present. The γδ T cells were also elevated during inflammation, reaching their peak at 72 h following induced inflammation. The percentage of apoptotic lymphocytes continually increased, with the highest proportion occurring 168 h after S. uberis infection. The results show that γδ T cells may be involved in the resolution of inflammation in bovine mammary glands, with the apoptosis of those cells potentially playing an important role.

Blackcurrant (Ribes nigrum L.) and Kamchatka Honeysuckle (Lonicera caerulea var. Kamtschatica) Extract Effects on Technological Properties, Sensory Quality, and Lipid Oxidation of Raw-Cooked Meat Product (Frankfurters).

Oxidation is one of the most prevalent factors responsible for meat product deterioration. Due to their potential health risks, commonly used synthetic antioxidants are beginning to be frowned upon by customers. The industry is searching for a natural replacement. In our study, we incorporated blackcurrant (Ribes nigrum L.) and Kamchatka honeysuckle (Lonicera caerulea var. Kamtschatica) extracts into raw-cooked meat products (frankfurters) as natural antioxidants. We observed that both extracts at concentrations of 3 mL·kg-1 were able to significantly (α = 0.05) postpone lipid oxidation in our samples, with results comparable to vitamin C (0.5 mg·kg-1) addition. Moreover, we did not observe negative effects of the extracts on the product's color, pH, or textural properties. Negative results were reported in the sensory evaluation of honeysuckle addition samples. This could have been caused by the natural strong and bitter taste of honeysuckle, which was transferred to the extracts and, subsequently, into the meat product.

Inflammation, It's Regulation and Antiphlogistic Effect of the Cyanogenic Glycoside Amygdalin.

The inflammatory reaction accompanies in part or in full any disease process in the vascularized metazoan. This complicated reaction is controlled by regulatory mechanisms, some of which produce unpleasant symptomatic manifestations of inflammation. Therefore, there has been an effort to develop selective drugs aimed at removing pain, fever, or swelling. Gradually, however, serious adverse side effects of such inhibitors became apparent. Scientific research has therefore continued to explore new possibilities, including naturally available substances. Amygdalin is a cyanogenic glycoside present, e.g., in bitter almonds. This glycoside has already sparked many discussions among scientists, especially about its anticancer potential and related toxic cyanides. However, toxicity at different doses made it generally unacceptable. Although amygdalin given at the correct oral dose may not lead to poisoning, it has not yet been accurately quantified, as its action is often affected by different intestinal microbial consortia. Its pharmacological activities have been studied, but its effects on the body's inflammatory response are lacking. This review discusses the chemical structure, toxicity, and current knowledge of the molecular mechanism of amygdalin activity on immune functions, including the anti-inflammatory effect, but also discusses inflammation as such, its mediators with diverse functions, which are usually targeted by drugs.

The Multiple Actions of Amygdalin on Cellular Processes with an Emphasis on Female Reproduction.

The present review summarizes the current knowledge on the provenance and properties, metabolism and toxicity, mechanism of action, physiological, and therapeutic roles of amygdalin-a molecule present in the seeds of apricot and other plants-with an emphasis on the action of amygdalin on reproductive processes, particularly in the female. Amygdalin influences physiological processes including female reproduction at various regulatory levels via extra- and intracellular signaling pathways regulating secretory activity, cell viability, steroidogenesis, proliferation, and apoptosis. On the other hand, while being metabolized in the body, amygdalin releases significant amounts of cyanide, which may lead to acute health hazard in those individuals who may be at risk. Despite some contradictions in the available data about benefits and toxic effects of amygdalin, its potential applicability at low doses may present a promising tool for regulation of various reproductive and other physiological processes including disease management primarily in cancer phytotherapy, animal production, medicine, and biotechnology. However, further research involving carefully designed dose-response studies is required to overcome the possible side effects of amygdalin and assure its safety as a therapeutic agent.

Enhancing Bioavailability of Nutraceutically Used Resveratrol and Other Stilbenoids.

Stilbenoids are interesting natural compounds with pleiotropic in vitro and in vivo activity. Their well-documented biological properties include anti-inflammatory effects, anticancer effects, effects on longevity, and many others. Therefore, they are nowadays commonly found in foods and dietary supplements, and used as a part of treatment strategy in various types of diseases. Bioactivity of stilbenoids strongly depends on different types of factors such as dosage, food composition, and synergistic effects with other plant secondary metabolites such as polyphenols or vitamins. In this review, we summarize the existing in vitro, in vivo, and clinical data from published studies addressing the optimization of bioavailability of stilbenoids. Stilbenoids face low bioavailability due to their chemical structure. This can be improved by the use of novel drug delivery systems or enhancers, which are discussed in this review. Current in vitro and in vivo evidence suggests that both approaches are very promising and increase the absorption of the original substance by several times. However, data from more clinical trials are required.

Scavenging Properties of Plant-Derived Natural Biomolecule Para-Coumaric Acid in the Prevention of Oxidative Stress-Induced Diseases.

Para-coumaric acid (p-CA) is a plant derived secondary metabolite belonging to the phenolic compounds. It is widely distributed in the plant kingdom and found mainly in fruits, vegetables, and cereals. Various in vivo and in vitro studies have revealed its scavenging and antioxidative properties in the reduction of oxidative stress and inflammatory reactions. This evidence-based review focuses on the protective role of p-CA including its therapeutic potential. p-CA and its conjugates possesses various bioactivities such as antioxidant, anti-inflammatory, anti-cancer, anti-diabetic, and anti-melanogenic properties. Due to its potent free radical scavenging activity, it can mitigate the ill effects of various diseases including arthritis, neurological disorders, and cardio-vascular diseases. Recent studies have revealed that p-CA can ameliorate the harmful effects associated with oxidative stress in the reproductive system, also by inhibiting enzymes linked with erectile function.

Physiological and Immune Functions of Punicalagin.

The aim of this publication is to compile a summary of the findings regarding punicalagin in various tissues described thus far in the literature, with an emphasis on the effect of this substance on immune reactions. Punicalagin (PUN) is an ellagitannin found in the peel of pomegranate (Punica granatum). It is a polyphenol with proven antioxidant, hepatoprotective, anti-atherosclerotic and chemopreventive activities, antiproliferative activity against tumor cells; it inhibits inflammatory pathways and the action of toxic substances, and is highly tolerated. This work describes the source, metabolism, functions and effects of punicalagin, its derivatives and metabolites. Furthermore, its anti-inflammatory and antioxidant effects are described.

Consumption of bitter apricot seeds affects lipid and endocrine profile in women.

Natural products have been attracting increasing attention in human diet, both due to the possible negative effects of synthetic food additives on human health and the increased consumer perception. Apricot seeds contain a wide variety of bioactive components and their consumption is associated with a reduced risk of chronic diseases. The objective of the present study was to evaluate the effect of consumption of bitter apricot seeds on blood lipid and endocrine profile in Slovak women (n = 18, 41.60 ± 11.28 years) of reproductive age. Volunteers consumed 60 mg.kg-1 of body weight of bitter apricot seeds divided into 8-12 doses daily for 42 days. During the experiment, three blood collections were carried out (at the beginning of the experiment - day 0, and after 21 and 42 days of consumption apricot seeds). Lipid profile was measured in terms of - total cholesterol (T-C, enzymatic photometric method), low-density cholesterol (LDL-C, calculated using the Friedewald equation), high-density cholesterol (HDL-C, direct clearance method), triglycerides (TG, enzymatic colorimetric method) whereas endocrine profile - follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), progesterone (P4), 17ß-estradiol (E2), testosterone, and androstenedione was assessed by ELISA. The blood levels of T-C, HDL-C and T-C did not change significantly (P > 0.05), however, the level of LDL-C decreased significantly (P < 0.05) after 42 days. On the other hand, there was a significant (P < 0.05) increase of T-C and TG after 21 days. The blood level of FSH, testosterone and androstenedione increased significantly (P < 0.05) although the levels of LH, PRL, P4 and E2 did not change (P > 0.05) after 42 days. The level of PRL and testosterone significantly (P < 0.05) increased and E2 significantly decreased after 21 days of apricot seeds consumption. The study suggests that daily consumption of apricot seeds may affect plasma lipid and endocrine profile in women of reproductive age.

Cyanogenic glycoside amygdalin influences functions of human osteoblasts in vitro.

Amygdalin has been promoted as an alternative cancer cure. However, it is still unclear how this cyanogenic glycoside affects non-cancer cells including bone cells. This study first investigated the impact of amygdalin on viability, morphology and expression of important genes in human osteoblasts in vitro. Primary human osteoblast cultures were exposed to amygdalin at concentrations 0; 0.1; 1 and 10 mg/mL in growth medium for 72 h. Cell viability, osteoblasts morphology and expression of 10 genes associated with osteoblast-specific pathways, oxidative stress and cell death were determined. Osteoblasts viability was significantly decreased (-27.26%) and their size was reduced (-23.20%) at the highest concentration of amygdalin (10 mg/mL). This concentration of amygdalin down-regulated the expression of COL1A1 and ALPL genes, whereas the expression of BGLAP, TNFSF11 and WNT5A genes was increased. The osteoblast cultivation with 0.1 mg/mL amygdalin caused down-regulation of COL1A1 gene. No changes in expression were determined for RUNX2, BAX, CASP1, SOD1 and GPX1 genes among all tested concentrations of amygdalin. In conclusion, amygdalin in a high concentration negatively affected mineralization of extracellular matrix, increased bone resorption and decreased osteoblast viability. These changes were accompanied by modified expression profiles of responsible genes.

Relationship between body conditions and environmental contaminants in bovine ovarian cells.

The effect of body condition and environmental contaminants on reproductive processes is known; however, it is not known whether basic ovarian cell functions and their response to these contaminants depend on body condition. This study aimed to understand the interrelationships between body conditions and environmental contaminants on ovarian cells. For this purpose, we compared ovarian granulosa cells isolated from cows with an emaciation tendency (body condition score, BCS2 on a scale from 1 to 5) and cows with average body condition (BCS3); proliferation, apoptosis, secretory activity and the response to environmental contaminants were all assessed in the cells. In the 1st series of experiments, ovarian granulosa cells isolated from BCS2 and BCS3 cows were cultured with and without benzene, xylene, and toluene (0.1%). The accumulation of nuclear and cytoplasmic markers of apoptosis (p53 and bax, respectively), a proliferation marker (PCNA), progesterone (P4), and insulin-like growth factor I (IGF-I) was evaluated by Western blot and radioimmunoassay (RIA) experiments. In the 2nd series of experiments, the groups of granulosa cells were cultured with and without mycotoxine deoxynivalenol (DON, 0, 10, 100, or 1000 ng/ml). The secretion of P4 and testosterone (T) was measured by RIA. In comparison to cells from BCS2 animals, ovarian cells isolated from BCS3 cows accumulated higher levels of bax and PCNA but not p53, and they secreted higher amounts of IGF-I but not P4 or T. In cells from BCS2 animals, benzene and xylene promoted p53 accumulation, and toluene reduced the accumulation. In the BCS2 group, all treatments promoted bax and PCNA expression. However, in cells from BCS3 animals, all environmental pollutants inhibited p53, toluene inhibited PCNA but not bax, and xylene did not affect the expression of proliferation or apoptosis markers. In the BCS2 group, P4 was inhibited by xylene, and IGF-I was stimulated by xylene but not by benzene or toluene. Low-dose exposure to DON (10 ng/ml) promoted P4 release from cells from both BCS2 and BCS3 animals, but high-dose exposure to DON (1000 ng/ml) reduced P4 secretion from the cells from BCS2 animals but not from the cells from BCS3 animals. The release of T was inhibited by high-dose exposure to DON (1000 ng/ml), irrespective of the BCS. An emaciation tendency reduces proliferation, apoptosis, and IGF-I release, and it induces or reverses the action of environmental contaminants on ovarian functions. Taken together, these observations demonstrate the effect of body condition and the direct influence of environmental contaminants on basic bovine ovarian functions. Furthermore, they demonstrate for the first time that the response of ovarian cells to environmental contaminants can be regulated by cow body condition.