Prenatal and neonatal exposure to the antiandrogen flutamide alters connexin 43 gene expression in adult porcine ovary

Durlej, Małgorzata; Knapczyk-Stwora, Katarzyna; Duda, Małgorzata; Kopera-Sobota, Ilona; Hejmej, Anna; Bilińska, Barbara; Słomczyńska, Maria

doi:10.1016/j.domaniend.2010.08.003

Cited by 28 publications

(20 citation statements)

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“…Although our mRNA data might suggest increased cell-to-cell communication within the fetal part of the placenta following flutamide treatment, unaffected protein level does not allow us to make that conclusion. The current results are in line with recent findings indicating Cx43 regulation by androgens in pigs (DURLEJ et al 2011a).…”

Section: Discussionsupporting

confidence: 93%

“…Studies on rats revealed that progesterone suppressed expression of Cx43 in endometrium during the receptive phase of pregnancy as well as during pseudopregnancy (GRUMMER et al 1999). Our previous study demonstrated that treatment of pregnant gilts with flutamide led to significant changes in the expression of Cx43 in the porcine ovary, corpus luteum and testis (DURLEJ et al 2011a, b), indicating direct or indirect Cx43 regulation by androgens. Therefore, the objective of the present study was to examine the potential changes in the Cx43 gene and protein expression in the placenta and uterus of pregnant pigs following blocking of AR with flutamide.…”

mentioning

confidence: 87%

“…Previously, we demonstrated that exposure to an antiandrogen flutamide during different times of gestation or neonatally affected porcine gonads functions during adulthood (DURLEJ et al 2011a, b). Androgen action is mediated via androgen receptors (ARs).…”

mentioning

confidence: 99%

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Influence of the Antiandrogen Flutamide on Connexin 43 (Cx43) Gene and Protein Expression in the Porcine Placenta and Uterus During Pregnancy

Wieciech¹,

Grzesiak²,

Knapczyk-Stwora³

et al. 2014

folia biol (krakow)

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WIECIECH I., GRZESIAK M., KNAPCZYK-STWORA K., PYTLIK A., S£OMCZYÑSKA M. 2014. Influence of the antiandrogen flutamide on connexin 43 (Cx43) gene expression in the porcine placenta and uterus during pregnancy. Folia Biologica (Kraków) 62: 367-375.The study focuses on the expression of connexin 43 (Cx43), a gap junctional protein in the porcine placenta and uterus. The aim was to examine Cx43 mRNA and protein expression after antiandrogen flutamide treatment. Flutamide was injected into pregnant gilts at a daily dose of 50 mg/kg body weight at different stages of pregnancy: between days 43-49 (50 dpc), 83-89 (90 dpc) and 101-107 (108 dpc) of gestation. The animals were sacrificed and tissues were collected one day after the last injection. Cx43 immunostaining was observed in epithelial and stromal cells of the fetal part of the placenta; luminal and glandular epithelial cells of maternal part of the placenta and myometrium of the uterus within placentation sites. Cx43 was also found in glandular epithelium and myometrium of non-placental uterus. Flutamide treatment caused fluctuations in Cx43 expression especially before parturition. Although significant changes in Cx43 mRNA expression were observed only in the fetal part of the placenta, Cx43 protein level was affected within the maternal part of the placenta and non-placental uterus. These results suggest the involvement of androgens in the regulation of Cx43 expression within the feto-maternal compartment in pigs. However, androgen deficiency caused pronounced changes during late pregnancy and before parturition. These results are interesting due to the functional changes in the porcine uterus during the preparturient period that is determined by Cx43 protein.

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Section: Discussionsupporting

confidence: 93%

mentioning

confidence: 87%

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Influence of the Antiandrogen Flutamide on Connexin 43 (Cx43) Gene and Protein Expression in the Porcine Placenta and Uterus During Pregnancy

Wieciech¹,

Grzesiak²,

Knapczyk-Stwora³

et al. 2014

folia biol (krakow)

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“…We have found ovarian morphological changes indicating delayed folliculogenesis in neonatal pigs exposed in utero to flutamide [59]. Abnormal folliculogenesis was also seen in prepubertal pigs, following prenatal period of anti-androgen exposure [60], whereas in adult animals, only neonatal time of flutamide treatment exerted disturbances marked by altered luteinization and corpus luteum cyst formation [61]. Apart from morphological disturbances, the altered follicular functioning in adulthood was manifested by changes in production of steroids (estradiol and androgens) and gonadotropins (FSH and LH), as well as in expression of genes involved in proper ovarian functioning, including AR, FSHR, aromatase, connexin 43, β-catenin, and aquaporin 5 [61][62][63].…”

Section: Eacs With Androgenic and Anti-androgenic Propertiesmentioning

confidence: 60%

“…Abnormal folliculogenesis was also seen in prepubertal pigs, following prenatal period of anti-androgen exposure [60], whereas in adult animals, only neonatal time of flutamide treatment exerted disturbances marked by altered luteinization and corpus luteum cyst formation [61]. Apart from morphological disturbances, the altered follicular functioning in adulthood was manifested by changes in production of steroids (estradiol and androgens) and gonadotropins (FSH and LH), as well as in expression of genes involved in proper ovarian functioning, including AR, FSHR, aromatase, connexin 43, β-catenin, and aquaporin 5 [61][62][63]. Furthermore, gestational or neonatal exposure to flutamide affected proliferation and apoptosis rates in large antral follicles of adult porcine ovary, which might influence the normal development of the follicles and pigs fertility as a consequence [64].…”

Section: Eacs With Androgenic and Anti-androgenic Propertiesmentioning

confidence: 94%

Endocrine Active Compounds Actions during Neonatal Period: Effect on the Ovary

Słomczyńska¹,

Grzesiak²,

Stwora³

2018

Selected Topics in Neonatal Care

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Many female reproductive disorders observed during adulthood originate from the neonatal period, which is a critical stage toward the reproductive potency. Human and animal fertility are determined by the pool of primordial follicles that are established during fetal or neonatal life. The earliest stages of follicle development are under control of a variety of factors, including sex steroids. Neonatal period is a "critical developmental window" in which organisms are susceptible to the environmental chemicals that may affect the reproductive health. Endocrine active compounds (EACs) are found abundantly in the environment and interfere with sex steroids (predominantly androgens and estrogens) by either mimicking or blocking their functions. This review covers the current knowledge about the effects of selected EACs with androgenic (testosterone propionate), anti-androgenic (flutamide), estrogenic (diethylstilbestrol, bisphenol A, 4-tert-octylphenol, phtalates and genistein), anti-estrogenic (ICI 182,780 and parabens), or mixed activity (methoxychlor) on the ovary of neonates, focusing on their effects on the early stages of folliculogenesis. These chemicals have been shown to affect oocyte survival, follicle formation, and growth, as well as steroidogenic functions. The better cognition of mechanisms underlying the long-term consequences of the neonatal EACs exposure may in future lead to an understanding of human health risks and developing prevention strategies.

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Di(2‐ethylhexyl)phthalate: Adverse effects on folliculogenesis that cannot be neglected

Zhang

Shen

Felici

et al. 2016

Environ and Mol Mutagen

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Primordial follicle formation and the subsequent transition of follicles through primary and secondary stages constitute crucial events of oogenesis. In particular, in mammals, defects in the processes that precede and accompany the formation of the primordial follicle pool can affect the size of this population significantly, while alterations in follicle activation, growth and maturation can result in premature depletion of the follicle reserve or cause follicle arrest at immature stages. Over the last decade, in vitro and in vivo approaches have been used to provide evidence that exposure to di(2-ethylhexyl)phthalate(DEHP), the most widely used plasticizer, has a deleterious effect on various stages of folliculogenesis in rodents. There is growing concern, supported by epidemiological and experimental data, that DEHP may have similar effects in women. This article reviews the evidence, with particular reference to our own findings, that DEHP may actually exert a variety of adverse effects on mammalian folliculogenesis from early to final stages of oogenesis, including altered development of the primordial germ cells, impaired fetal oocyte survival and meiotic progression, reduced oocyte nest breakdown, acceleration of primordial follicle activation, altered follicle steroidogenesis and increased follicle atresia. These effects can cause serious complications for reproductive and nonreproductive women's health. In addition, emerging data indicate that phthalates, including DEHP, may cause subtle epigenetic changes in germ cells that can be transmitted to subsequent generations, with potential negative effects on human health. Environ. Mol. Mutagen. 57:589-604, 2016. © 2016 Wiley Periodicals, Inc.

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Prenatal and neonatal exposure to the antiandrogen flutamide alters connexin 43 gene expression in adult porcine ovary

Cited by 28 publications

References 58 publications

Influence of the Antiandrogen Flutamide on Connexin 43 (Cx43) Gene and Protein Expression in the Porcine Placenta and Uterus During Pregnancy

Influence of the Antiandrogen Flutamide on Connexin 43 (Cx43) Gene and Protein Expression in the Porcine Placenta and Uterus During Pregnancy

Endocrine Active Compounds Actions during Neonatal Period: Effect on the Ovary

Di(2‐ethylhexyl)phthalate: Adverse effects on folliculogenesis that cannot be neglected

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