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Article ; Online: Discovery of new receptors regulating luteinizing hormone and follicle-stimulating hormone secretion by bovine gonadotrophs to explore a new paradigm for mechanisms regulating reproduction.

Kadokawa, Hiroya

The Journal of reproduction and development

2020 Volume 66, Issue 4, Page(s) 291–297

Abstract: Previous studies in the 1960s and 1970s have reported that both gonadotropin-releasing hormone (GnRH) and estradiol-activated nuclear estrogen receptors regulate gonadotropin secretion in women. However, I had previously reported that gonadotroph ... ...

Abstract	Previous studies in the 1960s and 1970s have reported that both gonadotropin-releasing hormone (GnRH) and estradiol-activated nuclear estrogen receptors regulate gonadotropin secretion in women. However, I had previously reported that gonadotroph function is regulated by complex crosstalk between several membrane receptors. RNA-seq had previously revealed 259 different receptor genes expressed in the anterior pituitary of heifers. However, the biological roles of most of these receptors remain unknown. I identified four new receptors of interest: G protein-coupled receptor 30 (GPR30), anti-Mullerian hormone (AMH) receptor type 2 (AMHR2), and G protein-coupled receptors 61 and 153 (GPR61 and GPR153). GPR30 rapidly (within a few minutes) mediates picomolar, but not nanomolar, levels of estradiol to suppress GnRH-induced luteinizing hormone (LH) secretion from bovine gonadotrophs, without decreasing mRNA expressions of the LHα, LHβ, or follicle-stimulating hormone (FSH) β subunits. GPR30 is activated by other endogenous estrogens, estrone and estriol. Moreover, GPR30 activation by zearalenone, a nonsteroidal mycoestrogen, suppresses LH secretion. AMHR2, activated by AMH, stimulates LH and FSH secretion, thus regulating gonadotrophs, where other TGF-β family members, including inhibin and activin, potentially affect FSH secretion. I also show that GPR61, activated by its ligand (recently discovered) significantly alters LH and FSH secretion. GPR61, GPR153, and AMHR2 co-localize with the GnRH receptor in unevenly dispersed areas of the bovine gonadotroph cell surface, probably lipid rafts. The findings summarized in this review reveal a new paradigm regarding the mechanisms regulating reproduction via novel receptors expressed on bovine gonadotrophs.
MeSH term(s)	Animals ; Cattle ; Female ; Follicle Stimulating Hormone/metabolism ; Gonadotrophs/metabolism ; Luteinizing Hormone/metabolism ; Pituitary Gland, Anterior/metabolism ; Receptors, Estrogen/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Receptors, LHRH/metabolism ; Receptors, Peptide/metabolism ; Receptors, Transforming Growth Factor beta/metabolism ; Reproduction/physiology
Chemical Substances	Receptors, Estrogen ; Receptors, G-Protein-Coupled ; Receptors, LHRH ; Receptors, Peptide ; Receptors, Transforming Growth Factor beta ; anti-Mullerian hormone receptor ; Luteinizing Hormone (9002-67-9) ; Follicle Stimulating Hormone (9002-68-0)
Language	English
Publishing date	2020-04-06
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	2039060-9
ISSN	1348-4400 ; 0916-8818
ISSN (online)	1348-4400
ISSN	0916-8818
DOI	10.1262/jrd.2020-012
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Specific locations and amounts of denatured collagen and collagen-specific chaperone HSP47 in the oviducts and uteri of old cows as compared with those of heifers.

Ferdousy, Raihana Nasrin / Kadokawa, Hiroya

Reproduction, fertility, and development

2022 Volume 34, Issue 8, Page(s) 619–632

Abstract: Collagen, the most abundant extra-cellular matrix in oviducts and uteri, performs critical roles in pregnancies. We hypothesised that the locations and amounts of both denatured collagen and the collagen-specific molecular chaperone 47-kDa heat shock ... ...

Abstract	Collagen, the most abundant extra-cellular matrix in oviducts and uteri, performs critical roles in pregnancies. We hypothesised that the locations and amounts of both denatured collagen and the collagen-specific molecular chaperone 47-kDa heat shock protein (HSP47) in the oviducts and uteri of old cows are different compared with those of young heifers because of repeated pregnancies. Since detecting damaged collagen in tissues is challenging, we developed a new method that uses a denatured collagen detection reagent. Then, we compared damaged collagen in the oviducts and uteri between post-pubertal growing nulliparous heifers (22.1±1.0months old) and old multiparous cows (143.1±15.6months old). Further, we evaluated the relationship between denatured collagen and HSP47 by combining this method with fluorescence immunohistochemistry. Picro-sirius red staining showed collagen in almost all parts of the oviducts and uteri. Expectedly, damaged collagen was increased in the oviducts and uteri of old cows. However, damaged collagen and HSP47 were not located in the same area in old cows. The number of fibroblasts increased, suggesting the presence of fibrosis in the oviducts and uteri of old cows. These organs of old cows showed higher HSP47 protein amounts than those of heifers. However, the uteri, but not oviducts, of old cows had lower HSP47 mRNA amounts than those of heifers. These findings revealed the specific location and amounts of denatured collagen and HSP47 in the oviducts and uteri of old cows compared with those of heifers.
MeSH term(s)	Aging ; Animals ; Cattle ; Collagen/metabolism ; Female ; HSP47 Heat-Shock Proteins/genetics ; HSP47 Heat-Shock Proteins/metabolism ; Molecular Chaperones ; Oviducts/metabolism ; Pregnancy ; Uterus/metabolism
Chemical Substances	HSP47 Heat-Shock Proteins ; Molecular Chaperones ; Collagen (9007-34-5)
Language	English
Publishing date	2022-03-16
Publishing country	Australia
Document type	Journal Article
ZDB-ID	1019913-5
ISSN	1448-5990 ; 1031-3613
ISSN (online)	1448-5990
ISSN	1031-3613
DOI	10.1071/RD21130
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Article ; Online: Anti-Müllerian hormone stimulates expression of the collagen-specific chaperone 47-kDa heat shock protein in bovine uterine epithelial cells.

Ferdousy, Raihana Nasrin / Kadokawa, Hiroya

Animal science journal = Nihon chikusan Gakkaiho

2022 Volume 93, Issue 1, Page(s) e13787

Abstract: Uterine collagen is the most abundant component of the uterine extracellular matrix and plays a critical role in pregnancy. The 47-kDa heat shock protein (HSP47) is the sole collagen-specific molecular chaperone. We investigated the mechanisms regulating ...

Abstract	Uterine collagen is the most abundant component of the uterine extracellular matrix and plays a critical role in pregnancy. The 47-kDa heat shock protein (HSP47) is the sole collagen-specific molecular chaperone. We investigated the mechanisms regulating the expression of HSP47 in the uterus by assessing the effect of anti-Müllerian hormone (AMH) stimulation on HSP47 expression in cultured bovine uterine epithelial cells. AMH receptor type 2 (AMHR2), AMH, and HSP47 expression was assessed by fluorescence immunocytochemistry in uterine epithelial layers of the uteri of Japanese Black cows. The effect of AMH on HSP47 expression was assessed in cultured epithelial cells. The effect of MEK/ERK inhibitor on AMH-induced HSP47 expression was also assessed. We confirmed the expression of AMHR2, AMH, and HSP47 in the uterine epithelial layers. We confirmed the expression of AMHR2, AMH, HSP47, and type IV collagen in cultured uterine epithelial cells. AMH treatment at 10 or 100 ng/ml promoted significant HSP47 expression (p < 0.05). MEK/ERK inhibitor U0126 pretreatment suppressed such AMH stimulation on HSP47. These findings indicate that AMH induced HSP47 protein expression through the ERK pathway in bovine uterine epithelial cells.
MeSH term(s)	Cattle ; Animals ; Female ; Anti-Mullerian Hormone/metabolism ; Heat-Shock Proteins/genetics ; Heat-Shock Proteins/metabolism ; Epithelial Cells/metabolism ; Collagen/metabolism ; Transforming Growth Factor beta/metabolism
Chemical Substances	Anti-Mullerian Hormone (80497-65-0) ; Heat-Shock Proteins ; Collagen (9007-34-5) ; Transforming Growth Factor beta
Language	English
Publishing date	2022-11-25
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2095161-9
ISSN	1740-0929 ; 1344-3941
ISSN (online)	1740-0929
ISSN	1344-3941
DOI	10.1111/asj.13787
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Article ; Online: Anti‐Müllerian hormone stimulates expression of the collagen‐specific chaperone 47‐kDa heat shock protein in bovine uterine epithelial cells

Ferdousy, Raihana Nasrin / Kadokawa, Hiroya

Animal Science Journal. 2022 Jan., v. 93, no. 1 p.e13787-

2022

Abstract: Uterine collagen is the most abundant component of the uterine extracellular matrix and plays a critical role in pregnancy. The 47‐kDa heat shock protein (HSP47) is the sole collagen‐specific molecular chaperone. We investigated the mechanisms regulating ...

Abstract	Uterine collagen is the most abundant component of the uterine extracellular matrix and plays a critical role in pregnancy. The 47‐kDa heat shock protein (HSP47) is the sole collagen‐specific molecular chaperone. We investigated the mechanisms regulating the expression of HSP47 in the uterus by assessing the effect of anti‐Müllerian hormone (AMH) stimulation on HSP47 expression in cultured bovine uterine epithelial cells. AMH receptor type 2 (AMHR2), AMH, and HSP47 expression was assessed by fluorescence immunocytochemistry in uterine epithelial layers of the uteri of Japanese Black cows. The effect of AMH on HSP47 expression was assessed in cultured epithelial cells. The effect of MEK/ERK inhibitor on AMH‐induced HSP47 expression was also assessed. We confirmed the expression of AMHR2, AMH, and HSP47 in the uterine epithelial layers. We confirmed the expression of AMHR2, AMH, HSP47, and type IV collagen in cultured uterine epithelial cells. AMH treatment at 10 or 100 ng/ml promoted significant HSP47 expression (p < 0.05). MEK/ERK inhibitor U0126 pretreatment suppressed such AMH stimulation on HSP47. These findings indicate that AMH induced HSP47 protein expression through the ERK pathway in bovine uterine epithelial cells.
Keywords	Wagyu ; animal science ; anti-Mullerian hormone ; cattle ; collagen ; epithelium ; extracellular matrix ; fluorescence ; heat shock proteins ; immunocytochemistry ; pregnancy ; protein synthesis ; uterus
Language	English
Dates of publication	2022-01
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	JOURNAL ARTICLE
ZDB-ID	2095161-9
ISSN	1740-0929 ; 1344-3941
ISSN (online)	1740-0929
ISSN	1344-3941
DOI	10.1111/asj.13787
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Article: Specific locations and amounts of denatured collagen and collagen-specific chaperone HSP47 in the oviducts and uteri of old cows as compared with those of heifers

Ferdousy, Raihana Nasrin / Kadokawa, Hiroya

Reproduction, fertility, and development. 2022, v. 34, no. 8

2022

Abstract	Collagen, the most abundant extra-cellular matrix in oviducts and uteri, performs critical roles in pregnancies. We hypothesised that the locations and amounts of both denatured collagen and the collagen-specific molecular chaperone 47-kDa heat shock protein (HSP47) in the oviducts and uteri of old cows are different compared with those of young heifers because of repeated pregnancies. Since detecting damaged collagen in tissues is challenging, we developed a new method that uses a denatured collagen detection reagent. Then, we compared damaged collagen in the oviducts and uteri between post-pubertal growing nulliparous heifers (22.1±1.0months old) and old multiparous cows (143.1±15.6months old). Further, we evaluated the relationship between denatured collagen and HSP47 by combining this method with fluorescence immunohistochemistry. Picro-sirius red staining showed collagen in almost all parts of the oviducts and uteri. Expectedly, damaged collagen was increased in the oviducts and uteri of old cows. However, damaged collagen and HSP47 were not located in the same area in old cows. The number of fibroblasts increased, suggesting the presence of fibrosis in the oviducts and uteri of old cows. These organs of old cows showed higher HSP47 protein amounts than those of heifers. However, the uteri, but not oviducts, of old cows had lower HSP47 mRNA amounts than those of heifers. These findings revealed the specific location and amounts of denatured collagen and HSP47 in the oviducts and uteri of old cows compared with those of heifers.
Keywords	collagen ; fibroblasts ; fibrosis ; fluorescence ; heat shock proteins ; immunohistochemistry
Language	English
Size	p. 619-632.
Publishing place	CSIRO Publishing
Document type	Article
ZDB-ID	1019913-5
ISSN	1448-5990 ; 1031-3613
ISSN (online)	1448-5990
ISSN	1031-3613
DOI	10.1071/RD21130
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Article ; Online: Chemosynthetic ethanolamine plasmalogen stimulates gonadotropin secretion from bovine gonadotrophs by acting as a potential GPR61 agonist.

Kadokawa, Hiroya / Yoshino, Ryunosuke / Saito, Risa / Hirokawa, Takatsugu

Animal reproduction science

2022 Volume 241, Page(s) 106992

Abstract: Brain ethanolamine plasmalogens (EPls) are unique alkenylacyl-glycerophospholipids and the only recognized ligands of G-protein-coupled receptor 61 (GPR61), a newly identified receptor that colocalizes with GnRH receptors on gonadotrophs. As the chemical ...

Abstract	Brain ethanolamine plasmalogens (EPls) are unique alkenylacyl-glycerophospholipids and the only recognized ligands of G-protein-coupled receptor 61 (GPR61), a newly identified receptor that colocalizes with GnRH receptors on gonadotrophs. As the chemical synthesis of EPl is challenging, only one chemosynthetic EPl, 1-(1Z-octadecenyl)- 2-oleoyl-sn-glycero-3-phosphoethanolamine (PLAPE; C18:0-C18:1), is commercially available. Therefore, we tested the hypothesis that PLAPE stimulates gonadotropin secretion from bovine gonadotrophs. We prepared anterior pituitary cells from healthy, post-pubertal heifers, cultured for 3.5 d, and then treated them with increasing concentrations (0, 0.5, 5, 50, or 500 pg/mL) of PLAPE for 5 mi, before either no treatment or GnRH stimulation. After 2 h, medium samples were harvested for FSH and LH assays. PLAPE (5-500 pg/mL) stimulated (P < 0.01) basal FSH and LH secretion, and such stimulation effects were inhibited by a SMAD pathway inhibitor. In the presence of GnRH, PLAPE at 0.5 and 5 pg/mL stimulated FSH and LH secretion (P < 0.01). However, a higher dose of PLAPE (500 pg/mL) suppressed GnRH-induced FSH and LH, and such suppressive effects were inhibited by an ERK pathway inhibitor. PLAPE stimulated gonadotropin secretion in the presence of EPls extracted from the brains of young heifers, but not old cows. Additionally, we performed in silico molecular-docking simulations using the deep-learning algorithm, AlphaFold2. The simulations revealed the presence of three binding sites for PLAPE in the three-dimensional structural model of GPR61. In conclusion, PLAPE stimulated gonadotropin secretion from bovine gonadotrophs and might act as a chemosynthetic agonist of GPR61.
MeSH term(s)	Animals ; Cattle ; Female ; Follicle Stimulating Hormone/metabolism ; Follicle Stimulating Hormone/pharmacology ; Gonadotrophs/metabolism ; Gonadotropin-Releasing Hormone/metabolism ; Gonadotropin-Releasing Hormone/pharmacology ; Plasmalogens/metabolism ; Plasmalogens/pharmacology
Chemical Substances	Plasmalogens ; phosphatidal ethanolamines ; Gonadotropin-Releasing Hormone (33515-09-2) ; Follicle Stimulating Hormone (9002-68-0)
Language	English
Publishing date	2022-05-13
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	429674-6
ISSN	1873-2232 ; 0378-4320
ISSN (online)	1873-2232
ISSN	0378-4320
DOI	10.1016/j.anireprosci.2022.106992
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Article ; Online: Specific locations and amounts of denatured collagen and collagen-specific chaperone HSP47 in the uterine cervices of old cows compared with those of heifers.

Ferdousy, Raihana Nasrin / Suong, Nguyen Thi / Kadokawa, Hiroya

Theriogenology

2022 Volume 196, Page(s) 10–17

Abstract: Collagen, the most abundant extra-cellular matrix in the reproductive tract, performs a critical role in pregnancy. Although detecting damaged collagen in tissues is challenging, we recently developed a new in situ detection method using a denatured ... ...

Abstract	Collagen, the most abundant extra-cellular matrix in the reproductive tract, performs a critical role in pregnancy. Although detecting damaged collagen in tissues is challenging, we recently developed a new in situ detection method using a denatured collagen detection reagent in bovine oviducts and uteri. Utilizing this method, we evaluated the hypothesis that the locations and amounts of denatured collagen in the uterine cervices of old cows are different from those in young heifers as a result of repeated pregnancies and deliveries. We compared damaged collagen in the uterine cervix at the mid-luteal phase between post-pubertal growing nulliparous heifers (22.1 ± 1.0 months old; n = 5) and old multiparous cows (143.1 ± 15.6 months old; 9 ± 1 parities; sacrificed at least 3 months after the last parturition by vaginal delivery; n = 5). Picrosirius red staining showed collagen in almost all parts of the cervices. Expectedly, the amount of damaged collagen was increased in the cervices of old cows. Additionally, we combined in situ detection and fluorescence immunohistochemistry of the collagen-specific molecular chaperone, the 47 kDa heat shock protein (HSP47). Increased HSP47 amounts were observed in the cervices from the old cows, but damaged collagen and HSP47 were not located in the same areas. The age differences were confirmed by western blotting using the anti-HSP47 antibody. These findings revealed the specific location and amounts of denatured collagen in the uterine cervices of old cows compared with those of heifers.
MeSH term(s)	Cattle ; Animals ; Female ; Collagen ; Molecular Chaperones
Chemical Substances	Collagen (9007-34-5) ; Molecular Chaperones
Language	English
Publishing date	2022-11-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	189232-0
ISSN	1879-3231 ; 0093-691X
ISSN (online)	1879-3231
ISSN	0093-691X
DOI	10.1016/j.theriogenology.2022.11.005
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Article: Chemosynthetic ethanolamine plasmalogen stimulates gonadotropin secretion from bovine gonadotrophs by acting as a potential GPR61 agonist

Kadokawa, Hiroya / Yoshino, Ryunosuke / Saito, Risa / Hirokawa, Takatsugu

Animal reproduction science. 2022 June, v. 241

2022

Abstract	Brain ethanolamine plasmalogens (EPls) are unique alkenylacyl-glycerophospholipids and the only recognized ligands of G-protein-coupled receptor 61 (GPR61), a newly identified receptor that colocalizes with GnRH receptors on gonadotrophs. As the chemical synthesis of EPl is challenging, only one chemosynthetic EPl, 1-(1Z-octadecenyl)− 2-oleoyl-sn-glycero-3-phosphoethanolamine (PLAPE; C18:0-C18:1), is commercially available. Therefore, we tested the hypothesis that PLAPE stimulates gonadotropin secretion from bovine gonadotrophs. We prepared anterior pituitary cells from healthy, post-pubertal heifers, cultured for 3.5 d, and then treated them with increasing concentrations (0, 0.5, 5, 50, or 500 pg/mL) of PLAPE for 5 mi, before either no treatment or GnRH stimulation. After 2 h, medium samples were harvested for FSH and LH assays. PLAPE (5–500 pg/mL) stimulated (P < 0.01) basal FSH and LH secretion, and such stimulation effects were inhibited by a SMAD pathway inhibitor. In the presence of GnRH, PLAPE at 0.5 and 5 pg/mL stimulated FSH and LH secretion (P < 0.01). However, a higher dose of PLAPE (500 pg/mL) suppressed GnRH-induced FSH and LH, and such suppressive effects were inhibited by an ERK pathway inhibitor. PLAPE stimulated gonadotropin secretion in the presence of EPls extracted from the brains of young heifers, but not old cows. Additionally, we performed in silico molecular-docking simulations using the deep-learning algorithm, AlphaFold2. The simulations revealed the presence of three binding sites for PLAPE in the three-dimensional structural model of GPR61. In conclusion, PLAPE stimulated gonadotropin secretion from bovine gonadotrophs and might act as a chemosynthetic agonist of GPR61.
Keywords	G-protein coupled receptors ; agonists ; algorithms ; animal reproduction ; anterior pituitary ; brain ; computer simulation ; ethanolamine ; ligands ; models ; secretion ; synthesis
Language	English
Dates of publication	2022-06
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	429674-6
ISSN	1873-2232 ; 0378-4320
ISSN (online)	1873-2232
ISSN	0378-4320
DOI	10.1016/j.anireprosci.2022.106992
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Article ; Online: Decreased Anti-Müllerian hormone and Anti-Müllerian hormone receptor type 2 in hypothalami of old Japanese Black cows.

Kereilwe, Onalenna / Kadokawa, Hiroya

The Journal of veterinary medical science

2020 Volume 82, Issue 8, Page(s) 1113–1117

Abstract: Cow fertility decreases with age, but the hypothalamic pathomechanisms are not understood. Anti-Müllerian hormone (AMH) stimulates gonadotropin-releasing hormone (GnRH) neurons via AMH receptor type 2 (AMHR2), and most GnRH neurons in the preoptic area ( ... ...

Abstract	Cow fertility decreases with age, but the hypothalamic pathomechanisms are not understood. Anti-Müllerian hormone (AMH) stimulates gonadotropin-releasing hormone (GnRH) neurons via AMH receptor type 2 (AMHR2), and most GnRH neurons in the preoptic area (POA), arcuate nucleus (ARC), and median eminence (ME) express AMH and AMHR2. Therefore, we hypothesized that both protein amounts would differ in the anterior hypothalamus (containing the POA) and posterior hypothalamus (containing the ARC and ME) between young post-pubertal heifers and old cows. Western blot analysis showed lower (P<0.05) expressions of AMH and AMHR2 in the posterior hypothalamus, but not in the anterior hypothalamus, of old Japanese Black cows compared to young heifers. Therefore, AMH and AMHR2 were decreased in the posterior hypothalami of old cows.
MeSH term(s)	Age Factors ; Animals ; Anti-Mullerian Hormone/metabolism ; Cattle ; Female ; Hypothalamus/metabolism ; Receptors, Peptide/genetics ; Receptors, Peptide/metabolism ; Receptors, Transforming Growth Factor beta/genetics ; Receptors, Transforming Growth Factor beta/metabolism
Chemical Substances	Receptors, Peptide ; Receptors, Transforming Growth Factor beta ; anti-Mullerian hormone receptor ; Anti-Mullerian Hormone (80497-65-0)
Language	English
Publishing date	2020-06-17
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1071753-5
ISSN	1347-7439 ; 0916-7250
ISSN (online)	1347-7439
ISSN	0916-7250
DOI	10.1292/jvms.20-0159
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Article ; Online: Reduced gonadotroph stimulation by ethanolamine plasmalogens in old bovine brains.

Kadokawa, Hiroya / Kotaniguchi, Miyako / Kereilwe, Onalenna / Kitamura, Shinichi

Scientific reports

2021 Volume 11, Issue 1, Page(s) 4757

Abstract: Ethanolamine plasmalogens (EPls), unique alkenylacyl-glycerophospholipids, are the only known ligands of G-protein-coupled receptor 61-a novel receptor co-localised with gonadotropin-releasing hormone receptors on anterior pituitary gonadotrophs. Brain ... ...

Abstract	Ethanolamine plasmalogens (EPls), unique alkenylacyl-glycerophospholipids, are the only known ligands of G-protein-coupled receptor 61-a novel receptor co-localised with gonadotropin-releasing hormone receptors on anterior pituitary gonadotrophs. Brain EPl decreases with age. Commercial EPl-extracted from the cattle brain (unidentified age)-can independently stimulate FSH secretion from gonadotrophs. We hypothesised that there exists an age-related difference in the quality, quantity, and ability of bovine brain EPls to stimulate bovine gonadotrophs. We compared the brains of young (about 26 month old heifers) and old (about 90 month old cows) Japanese Black bovines, including EPls obtained from both groups. Additionally, mRNA expressions of the EPl biosynthesis enzymes, glyceronephosphate O-acyltransferase, alkylglycerone phosphate synthase, and fatty acyl-CoA reductase 1 (FAR1) were evaluated in young and old hypothalami. The old-brain EPl did not stimulate FSH secretion from gonadotrophs, unlike the young-brain EPl. Molecular species of EPl were compared using two-dimensional liquid chromatography-mass spectrometry. We identified 20 EPl molecular species of which three and three exhibited lower (P < 0.05) and higher (P < 0.05) ratios, respectively, in old compared to young brains. In addition, quantitative reverse transcription-polymerase chain reaction detected higher FAR1 levels in the POA, but not in the ARC&ME tissues, of old cows than that of fertile young heifers. Therefore, old-brain EPl may be associated with age-related infertility.
MeSH term(s)	Age Factors ; Animals ; Brain/metabolism ; Cattle ; Female ; Follicle Stimulating Hormone/metabolism ; Gene Expression Regulation ; Gonadotrophs/drug effects ; Hypothalamus/chemistry ; Hypothalamus/enzymology ; Plasmalogens/chemistry ; Plasmalogens/metabolism ; Plasmalogens/pharmacology
Chemical Substances	Plasmalogens ; phosphatidal ethanolamines ; Follicle Stimulating Hormone (9002-68-0)
Language	English
Publishing date	2021-02-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-84306-6
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