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Patricia Franziska Siegenthaler, Peter Bain, Francesco Riva, Karl Fent
Synthetic progestins act as endocrine disrupters in fish but their risk to the environment is not sufficiently known. Here, we focused on an unexplored antiandrogenic progestin, chlormadinone acetate (CMA), and the antiandrogenic progestin cyproterone acetate (CPA). The aim was to evaluate whether their in vitro interaction with human and rainbowfish (Melanotaenia fluviatilis) sex hormone receptors is similar. Furthermore, we investigated their activity in zebrafish (Danio rerio) eleuthero-embryos. First, we studied agonistic and antagonistic activities of CMA, CPA, and 17α-ethinylestradiol (EE2), in recombinant yeast expressing either the human progesterone (PGR), androgen (AR), or estrogen receptor...
November 9, 2016: Aquatic Toxicology
Michela Candelma, Romain Fontaine, Sabrina Colella, Alberto Santojanni, Finn-Arne Weltzien, Oliana Carnevali
In vertebrates, the regulation of gametogenesis is under the control of gonadotropins (Gth), follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh). In fish, the physiological role of Gths is not fully understood, especially in species with asynchronous ovarian development. In order to elucidate the role of Gths in species with asynchronous ovary, we studied European hake (Merluccius merluccius) during the reproductive season. For this aim, we first cloned and sequenced both hormones. Then, we characterized their amino acid sequence and performed phylogenetic analyses to verify the relationship to their orthologues in other species...
November 1, 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
Fangjie Cao, Lizhen Zhu, Hui Li, Song Yu, Chengju Wang, Lihong Qiu
In the past few decades, extensive application of azoxystrobin has led to great concern regarding its adverse effects on aquatic organisms. The objective of the present study was to evaluate the reproductive toxicity of azoxystrobin to zebrafish. After adult zebrafish of both sexes were exposed to 2, 20 and 200 μg/L azoxystrobin for 21 days, egg production, the fertilization rate, the gonadosomatic index (GSI) and hepatosomatic index (HSI), 17β-estradiol (E2), testosterone (T) and vitellogenin (Vtg) concentrations, and histological alterations in the gonads and livers were measured...
September 8, 2016: Environmental Pollution
Huizhen Wang, Jacob May, Viktor Butnev, Bin Shuai, Jeffrey V May, George R Bousfield, T Rajendra Kumar
The hormone - specific FSHβ subunit of the human FSH heterodimer consists of N-linked glycans at Asn(7) and Asn(24) residues that are co-translationally attached early during subunit biosynthesis. Differences in the number of N-glycans (none, one or two) on the human FSHβ subunit contribute to macroheterogeneity in the FSH heterodimer. The resulting FSH glycoforms are termed hypo-glycosylated (FSH(21/18), missing either an Asn(24) or Asn(7) N-glycan chain on the β - subunit, respectively) or fully glycosylated (FSH(24), possessing of both Asn(7) and Asn(24) N-linked glycans on the β - subunit) FSH...
December 5, 2016: Molecular and Cellular Endocrinology
Takashi Tanaka, Mito Kanatsu-Shinohara, Zhenmin Lei, C V Rao, Takashi Shinohara
Spermatogenesis originates from self-renewal of spermatogonial stem cells (SSCs). Previous studies have reported conflicting roles of gonadotropic pituitary hormones in SSC self-renewal. Here, we explored the role of hormonal regulation of SSCs using Fshb and Lhcgr knockout (KO) mice. Although follicle-stimulating hormone (FSH) is thought to promote self-renewal by glial cell line-derived neurotrophic factor (GDNF), no abnormalities were found in SSCs and their microenvironment. In contrast, SSCs were enriched in Lhcgr-deficient mice...
August 9, 2016: Stem Cell Reports
Eun-Jin Kang, So-Hye Hong, Jae-Eon Lee, Seung Chul Kim, Hoe-Saeng Yang, Pyong In Yi, Sang-Myeong Lee, Beum-Soo An
Pregnenolone sulfate (PS) is a neuroactive steroid hormone produced in the brain. In this study, the effects of PS on synthesis and secretion of rat pituitary prolactin (PRL) were examined. To accomplish this, GH3 rat pituitary adenoma cells were treated with PS, which showed significantly increased mRNA and protein levels of PRL compared with the control. The mechanism of action responsible for the effects of PS on PRL synthesis and secretion was investigated by pretreating cells with inhibitors of traditional PRL- or the PS-related signaling pathway...
September 2016: Journal of Endocrinology
Louisa B Harding, Irvin R Schultz, Denis A M da Silva, Gina M Ylitalo, Dave Ragsdale, Stephanie I Harris, Stephanie Bailey, Barry V Pepich, Penny Swanson
It is well known that endocrine disrupting compounds (EDCs) present in wastewater treatment plant (WWTP) effluents interfere with reproduction in fish, including altered gonad development and induction of vitellogenin (Vtg), a female-specific egg yolk protein precursor produced in the liver. As a result, studies have focused on the effects of EDC exposure on the gonad and liver. However, impacts of environmental EDC exposure at higher levels of the hypothalamic-pituitary-gonad axis are less well understood...
September 2016: Aquatic Toxicology
Hamdi Mbarek, Conor V Dolan, Dorret I Boomsma
In a recent GWAS of spontaneous dizygotic twinning, Mbarek et al. (The American Journal of Human Genetics, 2016, Vol 98, pp. 898-908) identified two SNPs, rs11031006 (near FSHB) and rs17293443 (in SMAD3). In the present note, we address the question how to present the results in terms of effect sizes in a manner that is comprehensible to the general audience (e.g., mothers of twins, readership of newspapers). We propose to avoid the standard effect sizes such as odds ratios and relative risk as these require some knowledge of probability theory...
October 2016: Twin Research and Human Genetics: the Official Journal of the International Society for Twin Studies
Jean-Noël Laverrière, David L'Hôte, Laure Tabouy, Anne-Laure Schang, Bruno Quérat, Joëlle Cohen-Tannoudji
Gonadotrope cell identity genes emerge in a stepwise process during mouse pituitary development. Cga, encoding for the α-subunit of TSH, LH, and FSH, is initially detected at E11.5 followed by Gnrhr and steroidogenic factor Sf1 at E13.5, specifying cells engaged in a gonadotrope cell fate. Lhb and Fshb appear at E16.5 and 17.5, respectively, typifying differentiated gonadotrope cells. Using the αT1-1, αT3-1 and LβT2 cell lines recapitulating these stages of gonadotrope differentiation, DNA methylation at Gnrhr and Sf1 was investigated...
October 15, 2016: Molecular and Cellular Endocrinology
Olivia Smith Spicer, Ten-Tsao Wong, Nilli Zmora, Yonathan Zohar
Gnrh is the major neuropeptide regulator of vertebrate reproduction, triggering a cascade of events in the pituitary-gonadal axis that result in reproductive competence. Previous research in mice and humans has demonstrated that Gnrh/GNRH null mutations result in hypogonadotropic hypogonadism and infertility. The goal of this study was to eliminate gnrh3 (the hypophysiotropic Gnrh form) function in zebrafish (Danio rerio) to determine how ontogeny and reproductive performance are affected, as well as factors downstream of Gnrh3 along the reproductive axis...
2016: PloS One
Manuela Simoni, Daniele Santi, Luciano Negri, Ivan Hoffmann, Monica Muratori, Elisabetta Baldi, Marta Cambi, Marios Marcou, Thomas Greither, Enrica Baraldi, Simonetta Tagliavini, Daniela Carra, Francesco Lombardo, Loredana Gandini, Francesco Pallotti, Csilla Krausz, Giulia Rastrelli, Alberto Ferlin, Massimo Menegazzo, Elisa Pignatti, Francesca Linari, Marco Marino, Renzo Benaglia, Paolo E Levi-Setti, Hermann M Behre
STUDY QUESTION: Does the sperm DNA fragmentation index (DFI) improve depending on the FSH receptor (FSHR) genotype as assessed by the nonsynonymous polymorphisms rs6166 (p.N680S) after 3 months of recombinant FSH treatment in men with idiopathic infertility? SUMMARY ANSWER: FSH treatment significantly improves sperm DFI only in idiopathic infertile men with the p.N680S homozygous N FSHR. WHAT IS KNOWN ALREADY: FSH, fundamental for spermatogenesis, is empirically used to treat male idiopathic infertility and several studies suggest that DFI could be a candidate predictor of response to FSH treatment, in terms of probability to conceive...
September 2016: Human Reproduction
Louise Scheutz Henriksen, Casper P Hagen, Maria Assens, Alexander S Busch, Niels E Skakkebæk, Kristian Almstrup, Katharina M Main
CONTEXT: Single nucleotide polymorphisms altering FSH action (FSHB -211G>T, FSHR -29G>A, and FSHR 2039A>G) are associated with peripubertal and adult levels of reproductive hormones and age at pubertal onset in girls. OBJECTIVE: To investigate whether genetic polymorphisms altering FSH action affect serum levels of female reproductive hormones and breast development as early as during minipuberty. DESIGN: Longitudinal study. SETTING: Population-based cohort study...
August 2016: Journal of Clinical Endocrinology and Metabolism
Michelle R Jones, Mark O Goodarzi
The field of the genetics of polycystic ovary syndrome (PCOS) has relatively recently moved into the era of genome-wide association studies. This has led to the discovery of 16 robust loci for PCOS. Some loci contain genes with clear roles in reproductive (LHCGR, FSHR, and FSHB) and metabolic (INSR and HMGA2) dysfunction in the syndrome. The next challenge facing the field is the identification of causal variants and genes and the role they play in PCOS pathophysiology. The potential for gene discovery to improve diagnosis and treatment of PCOS is promising, though there is much to be done in the field before the current findings can be translated to the clinic...
July 2016: Fertility and Sterility
Hamdi Mbarek, Stacy Steinberg, Dale R Nyholt, Scott D Gordon, Michael B Miller, Allan F McRae, Jouke Jan Hottenga, Felix R Day, Gonneke Willemsen, Eco J de Geus, Gareth E Davies, Hilary C Martin, Brenda W Penninx, Rick Jansen, Kerrie McAloney, Jacqueline M Vink, Jaakko Kaprio, Robert Plomin, Tim D Spector, Patrik K Magnusson, Bruno Reversade, R Alan Harris, Kjersti Aagaard, Ragnar P Kristjansson, Isleifur Olafsson, Gudmundur Ingi Eyjolfsson, Olof Sigurdardottir, William G Iacono, Cornelis B Lambalk, Grant W Montgomery, Matt McGue, Ken K Ong, John R B Perry, Nicholas G Martin, Hreinn Stefánsson, Kari Stefánsson, Dorret I Boomsma
Spontaneous dizygotic (DZ) twinning occurs in 1%-4% of women, with familial clustering and unknown physiological pathways and genetic origin. DZ twinning might index increased fertility and has distinct health implications for mother and child. We performed a GWAS in 1,980 mothers of spontaneous DZ twins and 12,953 control subjects. Findings were replicated in a large Icelandic cohort and tested for association across a broad range of fertility traits in women. Two SNPs were identified (rs11031006 near FSHB, p = 1...
May 5, 2016: American Journal of Human Genetics
Ágnes Hunyadi-Bagi, Péter Balogh, Krisztina Nagy, Szilvia Kusza
Seven genes (BF, EGF, ESR, FSHB, H2AFZ, LEP and PRLP) were studied as candidate gene influencing eleven reproduction traits (interval between litters (IBL), percent of litter (PL), number of litters (NL), number of piglets born dead (NBD), number of piglet born alive (NBA), total number born (TNB), mean of born alive (MBA), mean of born dead (MBD), mean of born total (MBT), mean of piglets at 21 days of age (M21D) and growth rate (GR) in three pig breeds (Hungarian Large White (HLW), Duroc and Pietrain) by PCR-RFLP...
2016: Acta Biochimica Polonica
Cuili Wang, Dongteng Liu, Weiting Chen, Wei Ge, Wanshu Hong, Yong Zhu, Shi X Chen
Our previous study showed that the in vivo positive effects of 17α,20β-dihydroxy-4-pregnen-3-one (DHP), the major progestin in zebrafish, on early spermatogenesis was much stronger than the ex vivo ones, which may suggest an effect of DHP on the expression of gonadotropins. In our present study, we first observed that fshb and lhb mRNA levels in the pituitary of male adult zebrafish were greatly inhibited by 3 weeks exposure to 10nM estradiol (E2). However, an additional 24h 100nM DHP exposure not only reversed the E2-induced inhibition, but also significantly increased the expression of fshb and lhb mRNA...
July 2016: Journal of Endocrinology
Silvia Portela-Bens, Manuel Alejandro Merlo, María Esther Rodríguez, Ismael Cross, Manuel Manchado, Nadezda Kosyakova, Thomas Liehr, Laureana Rebordinos
The evolution of genes related to sex and reproduction in fish shows high plasticity and, to date, the sex determination system has only been identified in a few species. Solea senegalensis has 42 chromosomes and an XX/XY chromosome system for sex determination, while related species show the ZZ/ZW system. Next-generation sequencing (NGS), multi-color fluorescence in situ hybridization (mFISH) techniques, and bioinformatics analysis have been carried out, with the objective of revealing new information about sex determination and reproduction in S...
April 14, 2016: Chromosoma
Ghislaine Garrel, Chrystèle Racine, David L'Hôte, Chantal Denoyelle, Céline J Guigon, Nathalie di Clemente, Joëlle Cohen-Tannoudji
Anti-Müllerian hormone (AMH) contributes to male sexual differentiation and acts on gonads of both sexes. Identification of AMH receptivity in both pituitary and brain has led to the intriguing idea that AMH participates to the hypothalamic-pituitary control of reproduction, however in vivo experimental evidence is still lacking. We show that AMH stimulates secretion and pituitary gene expression of the gonadotropin FSH in vivo in rats. AMH action is sex-dependent, being restricted to females and occurring before puberty...
2016: Scientific Reports
Xiang Zhou, Ying Wang, Luisina Ongaro, Ulrich Boehm, Vesa Kaartinen, Yuji Mishina, Daniel J Bernard
Pituitary follicle-stimulating hormone (FSH) synthesis is regulated by transforming growth factorβsuperfamily ligands, most notably the activins and inhibins. Bone morphogenetic proteins (BMPs) also regulate FSHβ subunit (Fshb) expression in immortalized murine gonadotrope-like LβT2 cells and in primary murine or ovine primary pituitary cultures. BMP2 signals preferentially via the BMP type I receptor, BMPR1A, to stimulate murine Fshb transcription in vitro Here, we used a Cre-lox approach to assess BMPR1A's role in FSH synthesis in mice in vivo Gonadotrope-specific Bmpr1a knockout animals developed normally and had reproductive organ weights comparable with those of controls...
June 2016: Journal of Endocrinology
Ye Tian, Han Zhao, Haitao Chen, Yingqian Peng, Linlin Cui, Yanzhi Du, Zhao Wang, Jianfeng Xu, Zi-Jiang Chen
CONTEXT: A recent genome-wide association study (GWAS) has identified three susceptibility loci (8p32.1, 11p14.1, and 9q22.32) for polycystic ovary syndrome (PCOS) in women of European ancestry. The 9q22.32 locus was previously found in our Chinese PCOS GWAS. Replication of the other two loci is necessary to determine whether the same variants confer risk to PCOS in Han Chinese women. OBJECTIVE: This study aimed to investigate the effect of the European GWAS loci on PCOS susceptibility in Han Chinese women...
May 2016: Journal of Clinical Endocrinology and Metabolism
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