Apoptosis is a highly-regulated, active process of cell death involved in development, homeostasis and aging. Dysregulation of apoptosis leads to pathological states, such as cancer, developmental anomalies and degenerative diseases. Osteoarthritis (OA), the most common chronic joint disease in the elderly population, is characterized by progressive destruction of articular cartilage, resulting in significant disability. Because articular cartilage depends solely on its resident cells, the chondrocytes, for the maintenance of extracellular matrix, the compromising of chondrocyte function and survival would lead to the failure of the articular cartilage. The role of subchondral bone in the maintenance of proper cartilage matrix has been suggested as well, and it has been proposed that both articular cartilage and subchondral bone interact with each other in the maintenance of articular integrity and physiology. Some investigators include both articular cartilage and subchondral bone as targets for repairing joint degeneration. In late-stage OA, the cartilage becomes hypocellular, often accompanied by lacunar emptying, which has been considered as evidence that chondrocyte death is a central feature in OA progression. Apoptosis clearly occurs in osteoarthritic cartilage; however, the relative contribution of chondrocyte apoptosis in the pathogenesis of OA is difficult to evaluate, and contradictory reports exist on the rate of apoptotic chondrocytes in osteoarthritic cartilage. It is not clear whether chondrocyte apoptosis is the inducer of cartilage degeneration or a byproduct of cartilage destruction. Chondrocyte death and matrix loss may form a vicious cycle, with the progression of one aggravating the other, and the literature reveals that there is a definite correlation between the degree of cartilage damage and chondrocyte apoptosis. Because current treatments for OA act only on symptoms and do not prevent or cure OA, chondrocyte apoptosis would be a valid target to modulate cartilage degeneration.

Chondrocyte Apoptosis in the Pathogenesis of Osteoarthritis

Stress is an important factor that affects physical and mental status of a healthy person disturbing homeostasis of the body. Changes in the lifestyle are one of the major causes that lead to psychological stress. Psychological stress could impact the biology of female reproduction by targeting at the level of ovary, follicle and oocyte. The increased level of stress hormone such as cortisol reduces estradiol production possibly by affecting the granulosa cell functions within the follicle, which results deterioration in oocyte quality. Adaptation of lifestyle behaviours may generate reactive oxygen species (ROS) in the ovary, which further affects female reproduction. Balance between level of ROS and antioxidants within the ovary are important for maintenance of female reproductive health. Physiological level of ROS modulates oocyte functions, while its accumulation leads to oxidative stress (OS). OS triggers apoptosis in majority of germ cells within the ovary and even in ovulated oocytes. Although both mitochondria- as well as death-receptor pathways are involved in oocyte apoptosis, OS-induced mitochondria-mediated pathway plays a major role in the elimination of majority of germ cells from ovary. OS in the follicular fluid deteriorates oocyte quality and reduces reproductive outcome. On the other hand, antioxidants reduce ROS levels and protect against OS-mediated germ cell apoptosis and thereby depletion of germ cells from the ovary. Indeed, OS is one of the major factors that has a direct negative impact on oocyte quality and limits female reproductive outcome in several mammalian species including human.

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Impact of stress on oocyte quality and reproductive outcome.

In vitro maturation (IVM) is emerging as a popular technology at the forefront of fertility treatment and preservation. However, standard in vitro culture (IVC) conditions usually increase reactive oxygen species (ROS), which have been implicated as one of the major causes for reduced embryonic development. It is well-known that higher than physiological levels of ROS trigger granulosa cell apoptosis and thereby reduce the transfer of nutrients and survival factors to oocytes, which leads to apoptosis. ROS are neutralized by an elaborate defense system that consists of enzymatic and non-enzymatic antioxidants. The balance between ROS levels and antioxidants within IVM media are important for maintenance of oocytes that develop to the blastocyst stage. The effects of antioxidant supplementation of IVM media have been studied in various mammalian species. Therefore, this article reviews and summarizes the effects of ROS on oocyte quality and the use of antioxidant supplementations for IVM, in addition to its effects on maturation rates and further embryo development.

https://www.ijfs.ir/article_45416_0764e820ea499d2f0a726b0341e76b15.pdf

Reactive Oxygen Species Generation and Use of Antioxidants during In Vitro Maturation of Oocytes.

Reactive oxygen species (ROS) are required for cellular functioning and are controlled by anti-oxidants. The ROS influence the follicles, oocytes, endometrium, and their environment. The luteinizing hormone surge initiates a massive recruitment of ROS that modulates major reproductive functions namely, oocyte maturation, ovarian steroidogenesis, corpus luteal function, and luteolysis. The anti-oxidant system balances ROS generation and maintains the cellular functions. Both enzymatic and non-enzymatic anti-oxidants namely, vitamins and minerals are present in the follicles and protect the oocytes from the damaging effects of ROS. The overproduction of ROS leads to oxidative stress that affects the quality of oocytes and subsequent anovulation. Although researchers have tried to establish the role of ROS and anti-oxidants in oocyte development, still this aspect needs to be revisited. This review discusses the importance of the ROS and anti-oxidant balance that is required for the development and maturation of oocytes. There are increasing data on the activity of ROS and anti-oxidants in supporting oocyte development and maturation. However, extensive research is required to identify the safe physiological concentration and duration of both the ROS and anti-oxidants that are required to facilitate oocyte development and maturation during in vitro and in vivo conditions.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/rmb2.12013

Equilibrium between anti-oxidants and reactive oxygen species: a requisite for oocyte development and maturation.

// Teng Wang 1 , Jun Han 1 , Xing Duan 1 , Bo Xiong 1 , Xiang-Shun Cui 2 , Nam-Hyung Kim 2 , Hong-Lin Liu 1 , Shao-Chen Sun 1 1 College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China 2 Department of Animal Sciences, Chungbuk National University, Cheongju 361-763, Korea Correspondence to: Shao-Chen Sun, e-mail: sunsc@njau.edu.cn Keywords: BPA, cytoskeleton, autophagy/apoptosis, oxidative stress, epigenetics Received: January 20, 2016      Accepted: March 28, 2016      Published: April 11, 2016 ABSTRACT Bisphenol A (BPA) and Di-(2-ethylhexyl) phthalate (DEHP) are widely used in the plastic industry such as water bottles, containers, packaging and toys. BPA and DEHP are shown to be the endocrine disruptors which disturb the endocrine system and are linked to several diseases including infertility. In this study, we investigated the effects of BPA exposure on porcine oocyte maturation and its possible reasons. Our results showed that: (i) the rates of oocyte maturation significantly decreased with 250 μM BPA treatment in vitro , but not DEHP. This might be due to the delayed cell cycle progression of oocyte maturation. (ii) BPA treatment resulted in abnormal cytoskeletons on porcine oocytes, showing with aberrant actin distribution, spindle morphology and chromosome alignment, which was further confirmed by the reduced p-MAPK level. (iii) The fluorescence intensity of histone methylation (H3K4me2) and DNA methylation (5 mC) levels were altered after BPA treatment, indicating that epigenetic modification was disturbed. (iv) BPA-exposed oocytes had higher rates of early stage apoptosis/autophagy, and this may be resulted from the increased level of oxidative stress. Collectively, our results indicated that porcine oocytes maturation was disrupted after BPA treatment through disrupting cytoskeletal dynamics, epigenetic modifications and inducing apoptosis/autophagy.

/pdf/the-toxic-effects-and-possible-mechanisms-of-bisphenol-a-on-1f3rw7sunh.pdf

The toxic effects and possible mechanisms of Bisphenol A on oocyte maturation of porcine in vitro

Apoptosis causes elimination of more than 99% of germ cells from cohort of ovary through follicular atresia. Less than 1% of germ cells, which are culminated in oocytes further undergo apoptosis during last phases of oogenesis and depletes ovarian reserve in most of the mammalian species including human. There are several players that induce apoptosis directly or indirectly in oocytes at various stages of meiotic cell cycle. Premature removal of encircling granulosa cells from immature oocytes, reduced levels of adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate, increased levels of calcium (Ca(2+)) and oxidants, sustained reduced level of maturation promoting factor, depletion of survival factors, nutrients and cell cycle proteins, reduced meiotic competency, increased levels of proapoptotic as well as apoptotic factors lead to oocyte apoptosis. The BH3-only proteins also act as key regulators of apoptosis in oocyte within the ovary. Both intrinsic (mitochondria-mediated) as well as extrinsic (cell surface death receptor-mediated) pathways are involved in oocyte apoptosis. BID, a BH3-only protein act as a bridge between both apoptotic pathways and its cleavage activates cell death machinery of both the pathways inside the follicular microenvironment. Oocyte apoptosis leads to the depletion of ovarian reserve that directly affects reproductive outcome of various mammals including human. In this review article, we highlight some of the important players and describe the pathways involved during oocyte apoptosis in mammals.

Apoptosis in mammalian oocytes: a review.

Background: The excessive use of artificial sweeteners now a days just to lose weight and to remain fit and due to other reasons without knowing its effects on liver gave me a thought to conduct this study to see whether they are safe or not for liver health. Aim: To see the effects of artificial sweeteners Aspartame and Sucralose on the size of rat hepatocytes and to compare their effects to choose relatively safe artificial sweetener for routine use. Methods: Fifty adult Wistar albino rats used in this study were randomly divided into five groups. Group I (control group) animals were given drinking water by oral gavage. The animals of group II and III were given low (40mg/kg body weight) and high doses (1000mg/kg body weight) of Aspartame respectively. Similarly, animals of group IV and V were given low (5mg/kg body weight) and high doses (1000mg/kg body weight) of Sucralose respectively. Doses were given by oral gavage once daily, six days a week for a total duration of eight weeks. At the end of the experiment histological observation of liver in all animal groups was made. Results: Microscopic examination revealed that hepatocytes of group III animals (high dose group of Aspartame) had largest size with the mean value of 20.86±2.00µm as compared to the control group hepatocytes having mean value of 16.46±1.74µm. Conclusion: The increase in the size of hepatocytes was seen in high dose groups of Aspartame and Sucralose whereas changes seen in low dose groups of Aspartame and Sucralose were not significant. Keywords: Artificial sweeteners, Histology of rat liver, Size of hepatocytes.

https://pjmhsonline.com/index.php/pjmhs/article/download/2687/2652

Irfan Ali

Papers

Apoptosis in mammalian oocytes: a review.

Effects of Artificial Sweeteners Aspartame and Sucralose on the Size of Hepatocytes in Rat Liver