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Reproductive & Developmental Biology -0001; 39(1): 1-6

Published online November 30, -0001

https://doi.org/10.12749/RDB.2015.39.1.1

Copyright © The Korean Society of Animal Reproduction and Biotechnology.

Prostaglandin F Controls Reactive Oxygen Species in Bovine Corpus Luteum

Seunghyung Lee1,2, Boo-Keun Yang2, and Choon-Keun Park2,†

1Institute of Animal Resources, Kangwon National University, Chuncheon 200-701, Republic of Korea,
2College of Animal Life Science, Kangwon National University, Chuncheon 200-701, Republic of Korea

Correspondence to: Corresponding Author : Phone: +82-33-250-8627, parkck@kangwon.ac.kr

Received: December 9, 2014; Accepted: January 10, 2015

Luteolysis is a cyclical regression of the corpus luteum in many non-primate mammalian species. Prostaglandin F (PGF) from the uterus and ovary induces functional and structural luteolysis in bovine. The action of PGF is mediated by PGF receptor located on the luteal steroidogenic and endothelial cell membranes. PGF plays an important role in regulating nitric oxide production in endothelial cells of the bovine corpus luteum. Nitric oxide production and nitric oxide synthase activity are stimulated and induced by PGF in luteal endothelial cells. Moreover, the reactive oxygen species inhibits progesterone secretion in bovine luteal cells and induces apoptosis. Thus, the interaction between PGF and reactive oxygen species provides important aspects in physiology of the corpus luteum forfunctional and structural luteolysis.

Keywords: Prostaglandin F, Reactive oxygen species, Corpus luteum, Steroidogenic luteal cell, Endothelial cell

The oestrous cycle in bovine is characterized by repeated patterns of cellular proliferation, differentiation and transformation that accompany follicular development and the formation and regression of corpus luteum. The derived gonadotropin-releasing hormone and growth hormone from a pituitary are the primary regulation of final follicular maturation and corpus luteum function. The corpus luteum is a transient endocrine gland that produces progesterone, required for the establishment and maintenance of pregnancy. Also, luteolysis, the regression of corpus luteum, is initiated by prostaglandin F (PGF) and oxytocin hormones in cattle (Smith et al., 1998; Colazo et al., 2002; Repasi et al., 2005; Wenzinger et al., 2012; Schams et al., 2004). Recently, many studies have reported that reactive oxygen species is occurred in corpus luteum (Lee et al., 2010; Jones et al., 2008; Peltier et al., 2006; Rizzo et al., 2009; Sugino et al., 2006), however, it is unclear how luteolysis regulates with oxidative stress. This review will focus on the mechanisms and regulatory effects of PGF with reactive oxygen species in luteolysis in bovine corpus luteum.

Corpus luteum, yellow body in Latin, is hormone-secreting body in the female reproductive system. Corpus luteum is formed in an ovary at the site of a follicle, consists of steroidogenic large and small cells, endothelial cells, smooth muscle cells, immune cells, and fibroblasts (O’Shea et al.,1989). Specially, steroidogenic and endothelial cells are important factors for the regression of corpus luteum, steroidogenic cells secrete rogesterone and endothelial cells require the formation of new blood vessels and growth of corpus luteum. The main function of corpus luteum is to secrete progesterone during non-pregnant cycle and pregnancy. Luteal regression, luteolysis, is caused by releasing PGF from uterus at the end of the oestrous cycle. The function of formation and regression of the corpus luteum is regulated with many growth factors and hormones. Briefly, vascular and capillaries are up to 80% of the cells in mature corpus luteum (Lee et al., 2009; Rey- nolds et al., 1998). Thus, endothelial cell is potential factor for luteal growth and regression in bovine. In angiogenesis, vascular endothelial growth factor, acidic and basic fibroblast growth factors, insulin- like growth factors, angiopoietins, transforming growth factors family, tumor necrosis factor, vasoactive peptides-like angiotensin II, endothelin-1, and proteins of the extracellular matrix are important factors (Berisha et al., 2000; Augustin et al., 1998; Garrido et al., 1993; Goede et al., 1998; Einspanier et al., 1999; Schams et al., 2001; Schams et al., 2002; Vandehaar et al., 1995; Yancopoulos et al., 2000; Woad et al., 2000). In addition, the primary luteotropic hormones, luteinizing hormone and growth hormone, support corpus luteum for developing and growing. Luteinizing hormone stimulates the production and secretion of progesterone from steroidogenic small cells, also has their receptors (Niswender et al., 1998). Growth hormone is a main mediator for progesterone production in steroidogenic large cells (Niswender et al., 1985). Moreover, oxytocin and PGF are stimulated by growth hormone in bovine corpus luteum (Liebermann et al., 1994; Kobayashi et al., 2001).

The luteolysis is crucial to reset the ovarian cycle, has functional luteolysis and structural luteolysis (Hansel et al., 1996; Meidan et al., 1999; McCracken et al., 1999). Functional luteolysis is induced with prostaglandin F2alpha produced by reducing progesterone from the uterus. Structural luteolysis is processed by tissue degeneration and cell death of steroidogenic and endothelial cells, such as apoptosis.

A decrease of blood flow in bovine corpus luteum is an initial point for luteal regression. Acosta et al. and Knickerbocker et al. reported that progesterone concentration and luteal blood flow were low in PGF- induced luteolysis (Acosta et al., 2000; Acosta et al., 2002; Knickerbocker et al., 1988). However, PGF does not inhibit progesterone production in steroidogenic luteal cells in vitro (Alila et al., 1988; Okuda et al., 1998), but progesterone decreased in co-cultured with luteal endothelial cells and luteal cell (Girsh et al., 1996; Choudhary et al., 2005; Girsh et al., 1995). The above results suggest that endothelial cells in corpus luteum are crucial for inhibiting progesterone in functional luteolysis.

Recently, we reportedluteal endothelial cells isolated from bovine corpus luteum at the mid-luteal phase (days 8~12 of the oestrous cycle) and demonstrated that prostaglandin F2alpha receptor mRNA and protein expressions in luteal endothelial cell isolated from bovine corpus luteum (Lee et al., 2009). The mRNA of the receptor is not expressed in luteal endothelial cells isolated from early pregnant cow (Cavicchio et al., 2002). On the other hand, the isolated endothelial cells from corpus luteum express PGF receptor mRNA and protein (Cavicchio et al., 2002; Meidan et al., 2005; Mauluk et al., 1998). Endothelial cells in corpus luteum compose more than 50%, the function of luteal endothelial cells may be regulated in luteolysis.

Endothelial cell-regulated factors are vascular endothelial growth factor, acidic and basic fibroblast growth factors, insulin-like growth factors, angiopoietins, transforming growth factors family, tumor necrosis factor, vasoactive peptides-like angiotensin II, endothelin-1, and reactive oxygen species etc. In recent studies, nitric oxide produced by luteal endothelial cells inhibited progesterone secretion in bovine luteal cells (Skarzynski et al., 20000; Klipper et al., 2004). Also, nitric oxide regulates the regression of corpus luteum in many animals and human (Shirasuna et al., 2008; Skarzynski et al., 2000; Korzekwa et al., 2004; Skarzynski et al., 2003; Jaroszewski et al., 2000; Motta et al., 1999; Boiti et al., 2003; Vega et al., 1998). Therefore, our studies and other group studies suggest that nitric oxide has a physiological role for luteolysis in the bovine corpus luteum.

In addition, cytokines, tumor necrosis factor alpha, interlukin-1 beta, and interferon gamma, are increased by PGF. And, nitric oxide, angiotensin II, endothelin- 1and their receptor, fibroblast growth factors and their receptor are increased by cytokines. To know the mechanism of luteolysis regulating PGF, nitric oxide, and cytokines, the apoptotic mechanism is a key in finding functional luteolytic mechanism in the ovary.

After functional regression of the corpus luteum in bovine, structural luteolysis is continually started by PGF from the uterus and ovary (Lee et al., 2009; Silvia et al., 1991; Horton et al., 1976; Hansel et al., 1986). Vascular endothelial growth factor (VEGF) upregulates prostaglandin F2alpha in luteal endothelial cells. Neuvians et al. reported that vascular endothelial growth factor mRNA and protein level decreased in the collected luteal tissue after injection of PGF analogue (Neuvians et al., 2004). VEGF protein was not detected at 2 hour after prostaglandin F2alpha, also the mRNA and their receptors after 12 hour were downregulated. That means vascular endothelial growth factor in luteal endothelial cells regulates structural lutoelysis. Also, plasma progesterone decreased from 24 hour in bovine corpus luteum (Acosta et al., 2002).

Generally, luteal steroidogenic cells secrete progesterone. Although, progesterone is not inhibited by PGF in bovine luteal cells, a decrease of progesterone appears during luteal regression, suggesting that progesterone is mediated by other substances locally produced in the bovine corpus luteum, such as reactive oxygen species. In addition, cytokines were up-regulated during luteolysis, the receptors of luteinizing hormone and growth hormone, P450scc, and 3beta-hydroxysteroid dehydrogenase were down-regulated during structural luteolysis in bovine.

Reactive oxygen species includehydrogen peroxide, superoxide anion, oxygen, and nitric oxide. Nitric oxide isproduced by endothelial cells from corpus luteum inhibits progesterone and plays a luteolytic role in bovine (Klipper et al., 2004; Shirasuna et al., 2008; Skarzynski et al., 2000; Korzekwa et al.,2004; Skarzynski et al., 2003; Jaroszewski et al., 2000; Motta et al., 1999; Boiti et al., 2003; Vega et al., 1998). We also studied that an injection of PGF induces a transient increase in the concentrations of nitric oxide and partial pressure of oxygen in ovarian venous blood (Acosta et al., 2000; Acosta et al., 2002), suggesting nitric oxide from luteal endothelial cells mediates the luteolytic action of PGF in bovine.

Recently, we demonstrated that PGF stimulates nitric oxide production in the isolated luteal endothelial cells from bovine corpus luteum (Lee et al., 2009). Cultured bovine luteal endothelial cells expressed the m- RNA of prostaglandin F2alpha receptor. Also, nitric oxide was increased by PGF via inducing inducible nitric oxide synthase. Moreover, prostaglandin F2alpha stimulated nitric oxide synthase activity. In fact, nitric oxide synthase activity has been investigated in many cells, such as macrophages, endothelium, smooth muscle, ovarian stroma cells, and ovarian follicular granulose cells (Stuehr et al., 1985; Ignarro et al., 1987; Busse et al., 1990; Jablonka-Shariff et al., 1997; Van Voorhis et al., 1994). Moreover, nitric oxide regulates progesterone secretion in luteolytic and luteotropic factors in bovine (Boiti et al., 2000; Gobbetti et al., 1999). Therefore, we strongly assume that PGF enhances nitric oxide production by stimulating inducible nitric oxide synthase expression and nitric oxide synthaseactivity in bovine luteal endothelial cells.

In addition, eNOS mRNA expression was not changed by PGF in functional luteolysis, but apoptosis can occur. Since cytokines induce inducible nitric oxide synthase and stimulate nitric oxide levels. Thus, nitric oxide may also play a role in early functional luteolysis.

PGF regulating reactive oxygen species including nitric oxide in the luteal endothelial cells may play an important role for elucidating the local mechanisms of functional and structural luteolysis in the bovine corpus luteum.

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Article

ARTICLE

Reproductive & Developmental Biology -0001; 39(1): 1-6

Published online November 30, -0001 https://doi.org/10.12749/RDB.2015.39.1.1

Copyright © The Korean Society of Animal Reproduction and Biotechnology.

Prostaglandin F Controls Reactive Oxygen Species in Bovine Corpus Luteum

Seunghyung Lee1,2, Boo-Keun Yang2, and Choon-Keun Park2,†

1Institute of Animal Resources, Kangwon National University, Chuncheon 200-701, Republic of Korea,
2College of Animal Life Science, Kangwon National University, Chuncheon 200-701, Republic of Korea

Correspondence to:Corresponding Author : Phone: +82-33-250-8627, parkck@kangwon.ac.kr

Received: December 9, 2014; Accepted: January 10, 2015

Abstract

Luteolysis is a cyclical regression of the corpus luteum in many non-primate mammalian species. Prostaglandin F (PGF) from the uterus and ovary induces functional and structural luteolysis in bovine. The action of PGF is mediated by PGF receptor located on the luteal steroidogenic and endothelial cell membranes. PGF plays an important role in regulating nitric oxide production in endothelial cells of the bovine corpus luteum. Nitric oxide production and nitric oxide synthase activity are stimulated and induced by PGF in luteal endothelial cells. Moreover, the reactive oxygen species inhibits progesterone secretion in bovine luteal cells and induces apoptosis. Thus, the interaction between PGF and reactive oxygen species provides important aspects in physiology of the corpus luteum forfunctional and structural luteolysis.

Keywords: Prostaglandin F, Reactive oxygen species, Corpus luteum, Steroidogenic luteal cell, Endothelial cell

INTRODUCTION

The oestrous cycle in bovine is characterized by repeated patterns of cellular proliferation, differentiation and transformation that accompany follicular development and the formation and regression of corpus luteum. The derived gonadotropin-releasing hormone and growth hormone from a pituitary are the primary regulation of final follicular maturation and corpus luteum function. The corpus luteum is a transient endocrine gland that produces progesterone, required for the establishment and maintenance of pregnancy. Also, luteolysis, the regression of corpus luteum, is initiated by prostaglandin F (PGF) and oxytocin hormones in cattle (Smith et al., 1998; Colazo et al., 2002; Repasi et al., 2005; Wenzinger et al., 2012; Schams et al., 2004). Recently, many studies have reported that reactive oxygen species is occurred in corpus luteum (Lee et al., 2010; Jones et al., 2008; Peltier et al., 2006; Rizzo et al., 2009; Sugino et al., 2006), however, it is unclear how luteolysis regulates with oxidative stress. This review will focus on the mechanisms and regulatory effects of PGF with reactive oxygen species in luteolysis in bovine corpus luteum.

CORPUS LUTEUM IN BOVINE

Corpus luteum, yellow body in Latin, is hormone-secreting body in the female reproductive system. Corpus luteum is formed in an ovary at the site of a follicle, consists of steroidogenic large and small cells, endothelial cells, smooth muscle cells, immune cells, and fibroblasts (O’Shea et al.,1989). Specially, steroidogenic and endothelial cells are important factors for the regression of corpus luteum, steroidogenic cells secrete rogesterone and endothelial cells require the formation of new blood vessels and growth of corpus luteum. The main function of corpus luteum is to secrete progesterone during non-pregnant cycle and pregnancy. Luteal regression, luteolysis, is caused by releasing PGF from uterus at the end of the oestrous cycle. The function of formation and regression of the corpus luteum is regulated with many growth factors and hormones. Briefly, vascular and capillaries are up to 80% of the cells in mature corpus luteum (Lee et al., 2009; Rey- nolds et al., 1998). Thus, endothelial cell is potential factor for luteal growth and regression in bovine. In angiogenesis, vascular endothelial growth factor, acidic and basic fibroblast growth factors, insulin- like growth factors, angiopoietins, transforming growth factors family, tumor necrosis factor, vasoactive peptides-like angiotensin II, endothelin-1, and proteins of the extracellular matrix are important factors (Berisha et al., 2000; Augustin et al., 1998; Garrido et al., 1993; Goede et al., 1998; Einspanier et al., 1999; Schams et al., 2001; Schams et al., 2002; Vandehaar et al., 1995; Yancopoulos et al., 2000; Woad et al., 2000). In addition, the primary luteotropic hormones, luteinizing hormone and growth hormone, support corpus luteum for developing and growing. Luteinizing hormone stimulates the production and secretion of progesterone from steroidogenic small cells, also has their receptors (Niswender et al., 1998). Growth hormone is a main mediator for progesterone production in steroidogenic large cells (Niswender et al., 1985). Moreover, oxytocin and PGF are stimulated by growth hormone in bovine corpus luteum (Liebermann et al., 1994; Kobayashi et al., 2001).

PLAY OF PROSTAGLANDIN F2ALPHA IN LUTEOLYSIS

The luteolysis is crucial to reset the ovarian cycle, has functional luteolysis and structural luteolysis (Hansel et al., 1996; Meidan et al., 1999; McCracken et al., 1999). Functional luteolysis is induced with prostaglandin F2alpha produced by reducing progesterone from the uterus. Structural luteolysis is processed by tissue degeneration and cell death of steroidogenic and endothelial cells, such as apoptosis.

Functional Luteolysis

A decrease of blood flow in bovine corpus luteum is an initial point for luteal regression. Acosta et al. and Knickerbocker et al. reported that progesterone concentration and luteal blood flow were low in PGF- induced luteolysis (Acosta et al., 2000; Acosta et al., 2002; Knickerbocker et al., 1988). However, PGF does not inhibit progesterone production in steroidogenic luteal cells in vitro (Alila et al., 1988; Okuda et al., 1998), but progesterone decreased in co-cultured with luteal endothelial cells and luteal cell (Girsh et al., 1996; Choudhary et al., 2005; Girsh et al., 1995). The above results suggest that endothelial cells in corpus luteum are crucial for inhibiting progesterone in functional luteolysis.

Recently, we reportedluteal endothelial cells isolated from bovine corpus luteum at the mid-luteal phase (days 8~12 of the oestrous cycle) and demonstrated that prostaglandin F2alpha receptor mRNA and protein expressions in luteal endothelial cell isolated from bovine corpus luteum (Lee et al., 2009). The mRNA of the receptor is not expressed in luteal endothelial cells isolated from early pregnant cow (Cavicchio et al., 2002). On the other hand, the isolated endothelial cells from corpus luteum express PGF receptor mRNA and protein (Cavicchio et al., 2002; Meidan et al., 2005; Mauluk et al., 1998). Endothelial cells in corpus luteum compose more than 50%, the function of luteal endothelial cells may be regulated in luteolysis.

Endothelial cell-regulated factors are vascular endothelial growth factor, acidic and basic fibroblast growth factors, insulin-like growth factors, angiopoietins, transforming growth factors family, tumor necrosis factor, vasoactive peptides-like angiotensin II, endothelin-1, and reactive oxygen species etc. In recent studies, nitric oxide produced by luteal endothelial cells inhibited progesterone secretion in bovine luteal cells (Skarzynski et al., 20000; Klipper et al., 2004). Also, nitric oxide regulates the regression of corpus luteum in many animals and human (Shirasuna et al., 2008; Skarzynski et al., 2000; Korzekwa et al., 2004; Skarzynski et al., 2003; Jaroszewski et al., 2000; Motta et al., 1999; Boiti et al., 2003; Vega et al., 1998). Therefore, our studies and other group studies suggest that nitric oxide has a physiological role for luteolysis in the bovine corpus luteum.

In addition, cytokines, tumor necrosis factor alpha, interlukin-1 beta, and interferon gamma, are increased by PGF. And, nitric oxide, angiotensin II, endothelin- 1and their receptor, fibroblast growth factors and their receptor are increased by cytokines. To know the mechanism of luteolysis regulating PGF, nitric oxide, and cytokines, the apoptotic mechanism is a key in finding functional luteolytic mechanism in the ovary.

Structural Luteolysis

After functional regression of the corpus luteum in bovine, structural luteolysis is continually started by PGF from the uterus and ovary (Lee et al., 2009; Silvia et al., 1991; Horton et al., 1976; Hansel et al., 1986). Vascular endothelial growth factor (VEGF) upregulates prostaglandin F2alpha in luteal endothelial cells. Neuvians et al. reported that vascular endothelial growth factor mRNA and protein level decreased in the collected luteal tissue after injection of PGF analogue (Neuvians et al., 2004). VEGF protein was not detected at 2 hour after prostaglandin F2alpha, also the mRNA and their receptors after 12 hour were downregulated. That means vascular endothelial growth factor in luteal endothelial cells regulates structural lutoelysis. Also, plasma progesterone decreased from 24 hour in bovine corpus luteum (Acosta et al., 2002).

Generally, luteal steroidogenic cells secrete progesterone. Although, progesterone is not inhibited by PGF in bovine luteal cells, a decrease of progesterone appears during luteal regression, suggesting that progesterone is mediated by other substances locally produced in the bovine corpus luteum, such as reactive oxygen species. In addition, cytokines were up-regulated during luteolysis, the receptors of luteinizing hormone and growth hormone, P450scc, and 3beta-hydroxysteroid dehydrogenase were down-regulated during structural luteolysis in bovine.

PROSTAGLANDIN F2ALPHA AND REACTIVE OXYGEN SPECIES

Reactive oxygen species includehydrogen peroxide, superoxide anion, oxygen, and nitric oxide. Nitric oxide isproduced by endothelial cells from corpus luteum inhibits progesterone and plays a luteolytic role in bovine (Klipper et al., 2004; Shirasuna et al., 2008; Skarzynski et al., 2000; Korzekwa et al.,2004; Skarzynski et al., 2003; Jaroszewski et al., 2000; Motta et al., 1999; Boiti et al., 2003; Vega et al., 1998). We also studied that an injection of PGF induces a transient increase in the concentrations of nitric oxide and partial pressure of oxygen in ovarian venous blood (Acosta et al., 2000; Acosta et al., 2002), suggesting nitric oxide from luteal endothelial cells mediates the luteolytic action of PGF in bovine.

Recently, we demonstrated that PGF stimulates nitric oxide production in the isolated luteal endothelial cells from bovine corpus luteum (Lee et al., 2009). Cultured bovine luteal endothelial cells expressed the m- RNA of prostaglandin F2alpha receptor. Also, nitric oxide was increased by PGF via inducing inducible nitric oxide synthase. Moreover, prostaglandin F2alpha stimulated nitric oxide synthase activity. In fact, nitric oxide synthase activity has been investigated in many cells, such as macrophages, endothelium, smooth muscle, ovarian stroma cells, and ovarian follicular granulose cells (Stuehr et al., 1985; Ignarro et al., 1987; Busse et al., 1990; Jablonka-Shariff et al., 1997; Van Voorhis et al., 1994). Moreover, nitric oxide regulates progesterone secretion in luteolytic and luteotropic factors in bovine (Boiti et al., 2000; Gobbetti et al., 1999). Therefore, we strongly assume that PGF enhances nitric oxide production by stimulating inducible nitric oxide synthase expression and nitric oxide synthaseactivity in bovine luteal endothelial cells.

In addition, eNOS mRNA expression was not changed by PGF in functional luteolysis, but apoptosis can occur. Since cytokines induce inducible nitric oxide synthase and stimulate nitric oxide levels. Thus, nitric oxide may also play a role in early functional luteolysis.

CONCLUSION

PGF regulating reactive oxygen species including nitric oxide in the luteal endothelial cells may play an important role for elucidating the local mechanisms of functional and structural luteolysis in the bovine corpus luteum.

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