Beneficial Effects of Neurotrophin-4 Supplementation During in vitro Maturation of Porcine Cumulus-Oocyte Complexes and Subsequent Embryonic Development After Parthenogenetic Activation

Neurotrophin-4 (NT-4) is a neurotrophic factor that plays an important role in follicular development and oocyte maturation. However, it is not yet known whether NT-4 is related to oocyte maturation and follicular development in pigs. This study aims to investigate the effects of NT-4 supplementatio...

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Autores principales: Mirae Kim, Seon-Ung Hwang, Junchul David Yoon, Joohyeong Lee, Eunhye Kim, Lian Cai, Gahye Kim, Hyerin Choi, Dongjin Oh, Sang-Hwan Hyun
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:6816925bd6534335969a681142e7f4452021-11-12T05:27:23ZBeneficial Effects of Neurotrophin-4 Supplementation During in vitro Maturation of Porcine Cumulus-Oocyte Complexes and Subsequent Embryonic Development After Parthenogenetic Activation2297-176910.3389/fvets.2021.779298https://doaj.org/article/6816925bd6534335969a681142e7f4452021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fvets.2021.779298/fullhttps://doaj.org/toc/2297-1769Neurotrophin-4 (NT-4) is a neurotrophic factor that plays an important role in follicular development and oocyte maturation. However, it is not yet known whether NT-4 is related to oocyte maturation and follicular development in pigs. This study aims to investigate the effects of NT-4 supplementation during in vitro maturation (IVM) of porcine oocytes and subsequent embryonic development after parthenogenetic activation (PA). First, NT-4 and its receptors (TrkB and p75NTR) were identified through fluorescent immunohistochemistry in porcine ovaries. NT-4 was mainly expressed in theca and granulosa cells; phospho-TrkB and total TrkB were expressed in theca cells, granulosa cells, and oocytes; p75NTR was expressed in all follicular cells. During IVM, the defined maturation medium was supplemented with various concentrations of NT-4 (0, 1, 10, and 100 ng/mL). After IVM, the nuclear maturation rate was significantly higher in the 10 and 100 ng/mL NT-4 treated groups than in the control. There was no significant difference in the intracellular reactive oxygen species levels in any group after IVM, but the 1 and 10 ng/mL NT-4 treatment groups showed a significant increase in the intracellular glutathione levels compared to the control. In matured cumulus cells, the 10 ng/mL NT-4 treatment group showed significantly increased cumulus expansion-related genes and epidermal growth factor (EGF) signaling pathway-related genes. In matured oocytes, the 10 ng/mL treatment group showed significantly increased expression of cell proliferation-related genes, antioxidant-related genes, and EGF signaling pathway-related genes. We also investigated the subsequent embryonic developmental competence of PA embryos. After PA, the cleavage rates significantly increased in the 10 and 100 ng/mL NT-4 treatment groups. Although there was no significant difference in the total cell number of blastocysts, only the 10 ng/mL NT-4 treatment group showed a higher blastocyst formation rate than the control group. Our findings suggest that supplementation with the 10 ng/mL NT-4 can enhance porcine oocyte maturation by interacting with the EGF receptor signaling pathway. In addition, we demonstrated for the first time that NT-4 is not only required for porcine follicular development, but also has beneficial effects on oocyte maturation and developmental competence of PA embryos.Mirae KimMirae KimSeon-Ung HwangSeon-Ung HwangJunchul David YoonJunchul David YoonJoohyeong LeeJoohyeong LeeEunhye KimEunhye KimLian CaiLian CaiGahye KimGahye KimHyerin ChoiHyerin ChoiDongjin OhDongjin OhSang-Hwan HyunSang-Hwan HyunSang-Hwan HyunFrontiers Media S.A.articleneurotrophin-4pigfollicular developmentin vitro maturation of oocytesepidermal growth factorVeterinary medicineSF600-1100ENFrontiers in Veterinary Science, Vol 8 (2021)
institution DOAJ
collection DOAJ
language EN
topic neurotrophin-4
pig
follicular development
in vitro maturation of oocytes
epidermal growth factor
Veterinary medicine
SF600-1100
spellingShingle neurotrophin-4
pig
follicular development
in vitro maturation of oocytes
epidermal growth factor
Veterinary medicine
SF600-1100
Mirae Kim
Mirae Kim
Seon-Ung Hwang
Seon-Ung Hwang
Junchul David Yoon
Junchul David Yoon
Joohyeong Lee
Joohyeong Lee
Eunhye Kim
Eunhye Kim
Lian Cai
Lian Cai
Gahye Kim
Gahye Kim
Hyerin Choi
Hyerin Choi
Dongjin Oh
Dongjin Oh
Sang-Hwan Hyun
Sang-Hwan Hyun
Sang-Hwan Hyun
Beneficial Effects of Neurotrophin-4 Supplementation During in vitro Maturation of Porcine Cumulus-Oocyte Complexes and Subsequent Embryonic Development After Parthenogenetic Activation
description Neurotrophin-4 (NT-4) is a neurotrophic factor that plays an important role in follicular development and oocyte maturation. However, it is not yet known whether NT-4 is related to oocyte maturation and follicular development in pigs. This study aims to investigate the effects of NT-4 supplementation during in vitro maturation (IVM) of porcine oocytes and subsequent embryonic development after parthenogenetic activation (PA). First, NT-4 and its receptors (TrkB and p75NTR) were identified through fluorescent immunohistochemistry in porcine ovaries. NT-4 was mainly expressed in theca and granulosa cells; phospho-TrkB and total TrkB were expressed in theca cells, granulosa cells, and oocytes; p75NTR was expressed in all follicular cells. During IVM, the defined maturation medium was supplemented with various concentrations of NT-4 (0, 1, 10, and 100 ng/mL). After IVM, the nuclear maturation rate was significantly higher in the 10 and 100 ng/mL NT-4 treated groups than in the control. There was no significant difference in the intracellular reactive oxygen species levels in any group after IVM, but the 1 and 10 ng/mL NT-4 treatment groups showed a significant increase in the intracellular glutathione levels compared to the control. In matured cumulus cells, the 10 ng/mL NT-4 treatment group showed significantly increased cumulus expansion-related genes and epidermal growth factor (EGF) signaling pathway-related genes. In matured oocytes, the 10 ng/mL treatment group showed significantly increased expression of cell proliferation-related genes, antioxidant-related genes, and EGF signaling pathway-related genes. We also investigated the subsequent embryonic developmental competence of PA embryos. After PA, the cleavage rates significantly increased in the 10 and 100 ng/mL NT-4 treatment groups. Although there was no significant difference in the total cell number of blastocysts, only the 10 ng/mL NT-4 treatment group showed a higher blastocyst formation rate than the control group. Our findings suggest that supplementation with the 10 ng/mL NT-4 can enhance porcine oocyte maturation by interacting with the EGF receptor signaling pathway. In addition, we demonstrated for the first time that NT-4 is not only required for porcine follicular development, but also has beneficial effects on oocyte maturation and developmental competence of PA embryos.
format article
author Mirae Kim
Mirae Kim
Seon-Ung Hwang
Seon-Ung Hwang
Junchul David Yoon
Junchul David Yoon
Joohyeong Lee
Joohyeong Lee
Eunhye Kim
Eunhye Kim
Lian Cai
Lian Cai
Gahye Kim
Gahye Kim
Hyerin Choi
Hyerin Choi
Dongjin Oh
Dongjin Oh
Sang-Hwan Hyun
Sang-Hwan Hyun
Sang-Hwan Hyun
author_facet Mirae Kim
Mirae Kim
Seon-Ung Hwang
Seon-Ung Hwang
Junchul David Yoon
Junchul David Yoon
Joohyeong Lee
Joohyeong Lee
Eunhye Kim
Eunhye Kim
Lian Cai
Lian Cai
Gahye Kim
Gahye Kim
Hyerin Choi
Hyerin Choi
Dongjin Oh
Dongjin Oh
Sang-Hwan Hyun
Sang-Hwan Hyun
Sang-Hwan Hyun
author_sort Mirae Kim
title Beneficial Effects of Neurotrophin-4 Supplementation During in vitro Maturation of Porcine Cumulus-Oocyte Complexes and Subsequent Embryonic Development After Parthenogenetic Activation
title_short Beneficial Effects of Neurotrophin-4 Supplementation During in vitro Maturation of Porcine Cumulus-Oocyte Complexes and Subsequent Embryonic Development After Parthenogenetic Activation
title_full Beneficial Effects of Neurotrophin-4 Supplementation During in vitro Maturation of Porcine Cumulus-Oocyte Complexes and Subsequent Embryonic Development After Parthenogenetic Activation
title_fullStr Beneficial Effects of Neurotrophin-4 Supplementation During in vitro Maturation of Porcine Cumulus-Oocyte Complexes and Subsequent Embryonic Development After Parthenogenetic Activation
title_full_unstemmed Beneficial Effects of Neurotrophin-4 Supplementation During in vitro Maturation of Porcine Cumulus-Oocyte Complexes and Subsequent Embryonic Development After Parthenogenetic Activation
title_sort beneficial effects of neurotrophin-4 supplementation during in vitro maturation of porcine cumulus-oocyte complexes and subsequent embryonic development after parthenogenetic activation
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/6816925bd6534335969a681142e7f445
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