Developmental Biology

a worm

Dr. Rüdiger Schulz and Dr. Jan Bogerd

Research in the Reproductive Biology Group

Background

Reproduction is one of the major biological processes characteristic of all living species. In animals, sexual reproduction is the by far dominating mode of reproduction, although only half of the individuals (i.e. mothers) can produce offspring. The balance of this costly strategy is provided by the evolutionary advantage of the genetic recombination shuffle during meiosis in combination with sexual selection that exerts its pressure predominantly on males, the gender often providing little to the next generation beyond genes. The power of sexual selection is exemplified by extravagant traits for male-male competition in some species. Seemingly wasteful, these traits reflect the male’s competence to recruit resources from the environment and thus involve several genes spread over the genome. Females make use of these indicators of genome quality during mate choice.

The cellular basis of male reproduction are haploid spermatozoa, highly specialized cells functioning as motile genome vectors. Spermatozoa arise from a developmental process known as spermatogenesis. The process is fueled by spermatogonial stem cells and goes through three main phases: the initial mitotic phase, during which the number of spermatogonia increases rapidly, doubling with each round of mitosis; the meiotic phase (spermatocytes), during which genetic information is recombined and reduced to a haploid set; the final spermiogenic phase, during which the haploid spermatids emerging from meiosis differentiate, without further proliferation, into flagellated spermatozoa. Irrespective of the stage of development, germ cells cannot survive unless they receive support from a somatic cell type, known as Sertoli cells in vertebrates, which are in close, physical contact with the germ cells. In vertebrates, the endocrine system has evolved as master control system over spermatogenesis. Since Sertoli cells express the receptors for the two most important hormones regulating spermatogenesis, androgens produced in the testis and FSH produced in the pituitary, the Sertoli cell population is the main target of the endocrine regulation of spermatogenesis. However, also interstitial Leydig cells (producing androgens and growth factors) and peritubular myoid cells (producing growth factors) are testicular somatic cells responding to reproductive hormones and important for regulating spermatogenesis. The dependency on androgens links spermatogenesis to behavioral and morphological traits relevant in sexual selection.

Basic Research Question

Spermatogonial stem cells (SSCs) can be quiescent or cell-cycling. When cycling, they can either self-renew to produce more SSCs, or differentiate via a number of developmental stages into spermatozoa. The balance between self-renewal and differentiation is regulated. For example, SSC differentiation does not occur in juveniles, but is activated during puberty or the beginning of a reproductive season. Regulating the balance between self-renwal and differentiation is important also to avoid stem cell tumours or exhaustion of the SSC population. Paracrine factors derived from the stem cell’s environment determine this balance. Cell types contributing to this environment are Sertoli cells, myoid and Leydig and endothelial cells, that all are close to SSCs and contribute to the stem cell niche. The production and release of these factors is modulated by reproductive hormones, such as FSH and androgens. Information on the identity of these paracrine factors and their mode of action is largely missing in vertebrates. Hence, our main research question is, “How do hormones and growth factors regulate the proliferation and differentiation behavior of germ cells, in particular of spermatogonial stem cells?” Moreover, we are interested in what modulates production/release of hormones regulating spermatogenesis, in particular FSH.

Our experimental models are the zebrafish (Danio rerio), and in collaboration with other research groups (e.g., at the Institute of Marine Research in Bergen, Norway), also economically relevant species, such as the Atlantic salmon (Salmo salar).

Present Projects and Applied Aspects

The basic research concentrates on three aspects: (i) Identify candidate growth factors relevant for spermatogenesis via gene expression profiling (e.g. microarray; RNAseq [mRNA, miRNA, lncRNA]). (ii) Characterize the biological activity of identified candidate factors by expression profiling (RNAseq), loss-of-function as well as gain-of-function approaches. The functional approaches often use a primary testis tissue culture system for pharmacological approaches, or for testing recombinant hormones/growth factors; we also use genetic models, such as CRISPR/Cas-mediated gene knock out. (iii) Study the endocrine regulation of expression and/or release of identified candidate factors. And (iv) examine the endocrine regulation of pituitary FSH production and release. Points i to iii are mainly approached with the zebrafish model, points ii (in part) and iv (mainly) with the Atlantic salmon model. Finally, we start examining the use of nanobodies (salmon) but also GMO approaches (zebrafish) to induce sterility, a topic of great relevance for aquaculture biotechnology.

The equilibrium between stem cell self-renewal and differentiation is relevant also for applied research fields, such as aquaculture biotechnology and ecotoxicology. Considering aquaculture, sexual maturation or puberty poses significant economic, ecological, and animal welfare problems, for example for Atlantic salmon aquaculture. Puberty is associated with a switch from self-renewal to differentiation of stem cells. Understanding the physiological mechanisms controlling the switch in stem cell activity is the basis for developing approaches to delay the start of pubertal testis maturation. Moreover, sexually competent salmon escaping from aquaculture facilities (e.g. after storm-induced damage) bring about the risk of genetic introgression into native populations. Precocious male puberty and genetic introgression are two major problems limiting the further development of salmon aquaculture. The foreseeable decrease in resources versus increase in human population numbers, and several parameters of environmental relevance (e.g. feed conversion rate, carbon footprint, use of agricultural surface, protection of wild populations) place salmon aquaculture ahead of terrestrial animal protein production. However, the further improvement of this already rather efficient system requires attention. Considering ecotoxicology or endocrine disruption, it is in particular the expression profiling that provides several candidate genes as indicators for hormones or hormone-like substances that are found in surface freshwater bodies and affect the reproductive biology of freshwater species.

People

Current lab members:

  • (Associate Professor, UHD)
  • (Assistant Professor, UD)
  • (Professor emeritus)
  • (Research technician/head of aquarium)
  • (Ph.D. student)
  • (Master student)
  • (Master student)
  • paul.vanommeren (Master student)
  • (Master student)
  • (Animal caretaker)
  • (Animal caretaker)

Publications

Book Chapters

Schulz RW and Chauvigné F (2018) Spermatogenesis and spermiogenesis, Fish. In: Skinner MK (ed) Encyclopedia of Reproduction volume 6 (2nd edition), pp. 297-304. Academic Press: Elsevier. ISBN: 9780128118993

Andersson E, Taranger GL, Wargelius A, Schulz RW (2018) Puberty in fish. In: Skinner MK (ed) Encyclopedia of Reproduction volume 6 (2nd edition), pp. 426-429. Academic Press: Elsevier. ISBN: 9780128118993

França LR, Nóbrega RHb, Morais RDVS, de Castro Assis LH, and Schulz RW (2015) Sertoli cell structure and function in anamniote vertebrates. In: Griswold MD (ed) Sertoli cell biology (2nd edition), pp. 385-407. Amsterdam: Elsevier. ISBN: 978-0-12-417047-6

Schulz RW and Nobrega RH (2011) Anatomy and Histology of Fish Testis. In: Farrell A.P., (ed.), Encyclopedia of Fish Physiology: From Genome to Environment, volume 1, pp. 616–626. San Diego: Academic Press

Schulz R.W. and Nobrega R.H. (2011) Regulation of Spermatogenesis. In: Farrell A.P., (ed.), Encyclopedia of Fish Physiology: From Genome to Environment, volume 1, pp. 627–634. San Diego: Academic Press.

Peer-reviewed publications (2019 - 2001)

Publications from RW Schulz older than 2001 can be viewed under ORCID, PUBLONS/RESEARCHER-ID , or Google Scholar

2019

Schulz RW, Taranger GL, Bogerd J, Nijenhuis W, Norberg B, Male R, Andersson E (2019) Entry into puberty is reflected in changes in hormone production but not in testicular receptor expression in Atlantic salmon (Salmo salar). Reprod Biol Endocrinol 17(1):48 doi: 10.1186/s12958-019-0493-8. PMID: 31226998. Erratum in: Reprod Biol Endocrinol 2019 17(1):57. PMID: 31226998

Crespo D, Bogerd J, Sambroni E, LeGac F, Andersson E, Edvardsen RB, Bergman EJ, Björnsson BT, Taranger GL, Schulz RW (2019) The initiation of puberty in Atlantic salmon brings about large changes in testicular gene expression that are modulated by the energy status. BMC Genomics 20(1):475 doi: 10.1186/s12864-019-5869-9. PMID: 31185904

Crespo D, Assis LHC, van de Kant HJG, de Waard S, Safian D, Lemos MS, Bogerd J, Schulz RW (2019) Endocrine and local signaling interact to regulate spermatogenesis in zebrafish: Follicle-stimulating hormone, retinoic acid and androgens. Development doi: 10.1242/dev.178665. PMID: 31597660

Crespo D, Lemos MS, Zhang YT, Safian D, Norberg B, Bogerd J, Schulz R (2019) PGE2 inhibits spermatogonia differentiation in zebrafish: interaction with Fsh and an androgen. J Endocrinol doi: 10.1530/JOE-19-0309. PMID: 31600720

Safian D, Bogerd J, Schulz RW (2019) Regulation of spermatogonial development by Fsh: The complementary roles of locally produced Igf and Wnt signaling molecules in adult zebrafish testis. Gen Comp Endocrinol 284:113244 doi: 10.1016/j.ygcen.2019.113244. PMID: 31415728

Fraser TWK, Fjelldal PG, Schulz RW, Norberg B, Hansen TJ (2019) Termination of puberty in out-of-season male Atlantic salmon smolts. Comp Biochem Physiol A Mol Integr Physiol 232:60-66 doi: 10.1016/j.cbpa.2019.03.011. Erratum in: Comp Biochem Physiol A Mol Integr Physiol 235:227-228. PMID: 3088583110

Kruger AN, Brogley MA, Huizinga JL, Kidd JM, de Rooij DG, Hu YC, Mueller JL (2019) A neofunctionalized X-linked ampliconic gene family is essential for male fertility and equal sex ratio in mice. Curr Biol doi: 10.1016/j.cub.2019.08.057. PMID: 31630956

Gómez-H L, Felipe-Medina N, Condezo YB, Garcia-Valiente R, Ramos I, Suja JA, Barbero JL, Roig I, Sánchez-Martín M, de Rooij DG, Llano E, Pendas AM (2019) The PSMA8 subunit of the spermatoproteasome is essential for proper meiotic exit and mouse fertility. PLoS Genet 15(8):e1008316 doi: 10.1371/journal.pgen.1008316. PMID: 31437213

Sohni A, Tan K, Song HW, Burow D, de Rooij DG, Laurent L, Hsieh TC, Rabah R, Hammoud SS, Vicini E, Wilkinson MF (2019) The neonatal and adult human testis defined at the single-cell level. Cell Rep 26(6):1501-1517 doi: 10.1016/j.celrep.2019.01.045. PMID: 30726734

Ciani E, Fontaine R, Maugars G, Nourizadeh-Lillabadi R, Andersson E, Bogerd J, von Krogh K, Weltzien FA (2019) Gnrh receptor gnrhr2bbα is expressed exclusively in lhb-expressing cells in Atlantic salmon male parr. Gen Comp Endocrinol 285:113293 doi: 10.1016/j.ygcen.2019.113293. PubMed PMID: 31580881

Alnafea H, Vahkal B, Zelmer CK, Yegorov S, Bogerd J, Good SV (2019) Japanese medaka as a model for studying the relaxin family genes involved in neuroendocrine regulation: Insights from the expression of fish-specific rln3 and insl5 and rxfp3/4-type receptor paralogues. Mol Cell Endocrinol 487:2-11 doi: 10.1016/j.mce.2019.01.017. PMID: 30703485

2018

Safian D, Ryane N, Bogerd J, Schulz RW (2018) Fsh stimulates Leydig cell Wnt5a production, enriching zebrafish type A spermatogonia. J Endocrinol 239(3):351-363 doi: 10.1530/JOE-18-0447. PMID: 30400013

Safian D, Bogerd J, Schulz RW (2018) Igf3 activates β-catenin signaling to stimulate spermatogonial differentiation in zebrafish. J Endocrinol 238(3):245-257 doi: 10.1530/JOE-18-0124. PMID: 29941503

Fjelldal PG, Schulz R, Nilsen TO, Andersson E, Norberg B, Hansen TJ (2018) Sexual maturation and smoltification in domesticated Atlantic salmon (Salmo salar L.) - is there a developmental conflict? Physiol Rep 6(17):e13809 doi: 10.14814/phy2.13809. PMID: 30175449

Kjærner-Semb E, Ayllon F, Kleppe L, Sørhus E, Skaftnesmo K, Furmanek T, Segafredo FT, Thorsen A, Fjelldal PG, Hansen T, Taranger GL, Andersson E, Schulz RW, Wargelius A, Edvardsen RB (2018) Vgll3 and the Hippo pathway are regulated in Sertoli cells upon entry and during puberty in Atlantic salmon testis. Sci Rep 8(1):1912 doi: 10.1038/s41598-018-20308-1. PMID: 29382956

de Castro Assis LH, de Nóbrega RH, Gómez-González NE, Bogerd J, Schulz RW (2018) Estrogen-induced inhibition of spermatogenesis in zebrafish is largely reversed by androgen. J Mol Endocrinol 60(4):273-284 doi: 10.1530/JME-17-0177. PMID: 29476039

Hamer G, de Rooij DG (2018) Mutations causing specific arrests in the development of mouse primordial germ cells and gonocytes. Biol Reprod 99(1):75-86 doi: 10.1093/biolre/ioy075. PMID: 29590307

Hirota T, Blakeley P, Sangrithi MN, Mahadevaiah SK, Encheva V, Snijders AP, ElInati E, Ojarikre OA, de Rooij DG, Niakan KK, Turner JMA (2018) SETDB1 Links the Meiotic DNA Damage Response to Sex Chromosome Silencing in Mice. Dev Cell 47(5):645-659 doi: 10.1016/j.devcel.2018.10.004. PMID: 30393076

Gregoire EP, Stevant I, Chassot AA, Martin L, Lachambre S, Mondin M, de Rooij DG, Nef S, Chaboissier MC (2018) NRG1 signalling regulates the establishment of Sertoli cell stock in the mouse testis. Mol Cell Endocrinol 478:17-31 doi: 10.1016/j.mce.2018.07.004. PMID: 30040984

Bathgate RAD, Kocan M, Scott DJ, Hossain MA, Good SV, Yegorov S, Bogerd J, Gooley PR (2018) The relaxin receptor as a therapeutic target - perspectives from evolution and drug targeting. Pharmacol Ther 187: 114-132 doi: 10.1016/j.pharmthera.2018.02.008. PMID: 29458108

Ricci JMB, Martinez ERM, Butzge AJ, Doretto LB, Oliveira MA, Bombardelli RA, Bogerd J, Nóbrega RH (2018) Characterization of vasa homolog in a neotropical catfish, Jundiá (Rhamdia quelen): Molecular cloning and expression analysis during embryonic and larval development. Gene 654:116-126 doi: 10.1016/j.gene.2018.02.029. PMID: 29454090

2017

Morais RDVS, Crespo D, Nóbrega RH, Lemos MS, van de Kant HJG, de França LR, Male R, Bogerd J, Schulz RW (2017) Antagonistic regulation of spermatogonial differentiation in zebrafish (Danio rerio) by Igf3 and Amh. Mol Cell Endocrinol 454:112-124 DOI: 10.1016/j.mce.2017.06.017. PMID: 28645700

Kleppe L, Andersson E, Skaftnesmo KO, Edvardsen RB, Fjelldal PG, Norberg B, Bogerd J, Schulz RW, Wargelius A (2017) Sex steroid production associated with puberty is absent in germ cell-free salmon. Sci Rep 7(1):12584 DOI: 10.1038/s41598-017-12936-w. PMID: 28974703

Skaftnesmo KO, Edvardsen RB, Furmanek T, Crespo D, Andersson E, Kleppe L, Taranger GL, Bogerd J, Schulz RW, Wargelius A (2017) Integrative testis transcriptome analysis reveals differentially expressed miRNAs and their mRNA targets during early puberty in Atlantic salmon. BMC Genomics 18(1):801 DOI: 10.1186/s12864-017-4205-5. PMID: 29047327

Safian D, van der Kant HJG, Crespo D, Bogerd J, Schulz RW (2017) Follicle-stimulating hormone regulates igfbp gene expression directly or via downstream effectors to modulate Igf3 effects on zebrafish spermatogenesis. Front Endocrinol (Lausanne) DOI: 10.3389/fendo.2017.00328 PMID: 29209278

ElInati E, Russell HR, Ojarikre OA, Sangrithi M, Hirota T, de Rooij DG, McKinnon PJ, Turner JMA (2017) DNA damage response protein TOPBP1 regulates X chromosome silencing in the mammalian germ line. PNAS 114(47): 12536-12541 doi: 10.1073/pnas.1712530114. PMID: 29114052

de Rooij DG (2017) The nature and dynamics of spermatogonial stem cells. Development 144(17): 3022-3030. doi: 10.1242/dev.146571. PMID: 28851723

de Jesus LWO, Bogerd J, Vieceli FM, Branco GS, Camargo MP, Cassel M, Moreira RG, Yan CYI, Borella MI (2017) Gonadotropin subunits of the characiform Astyanax altiparanae: Molecular characterization, spatiotemporal expression and their possible role on female reproductive dysfunction in captivity. Gen Comp Endocrinol 246: 150-163 DOI: 10.1016/j.ygcen.2016.12.004. PMID: 27940043

2016

Safian D, Morais RD, Bogerd J, Schulz RW (2016) Igf binding proteins protect undifferentiated spermatogonia in the zebrafish testis against excessive differentiation. Endocrinology DOI: 10.1210/en.2016-1315 PMID: 27689414

Crespo D, Assis LH, Furmanek T, Bogerd J, Schulz RW (2016) Expression profiling identifies Sertoli and Leydig cell genes as Fsh targets in adult zebrafish testis. Mol Cell Endocrinol 437, 237-251 PMID: 27566230

Wargelius A, Leininger S, Skaftnesmo KO, Kleppe L, Andersson E, Taranger GL, Schulz RW, Edvardson RB (2016) Dnd knockout ablates germ cells and demonstrates germ cell independent sex differentiation in Atlantic salmon. Sci Rep 6, 21284 DOI: 10.1038/srep21284 PMID: 26888627

Assis LH, Crespo D, Morais RD, França LR, Bogerd J, Schulz RW (2016) INSL3 stimulates spermatogonial differentiation in testis of adult zebrafish (Danio rerio). Cell Tissue Res. 363, 579-588 PMID: 26077926.

Kuradomi RY, De Souza TG, Foresti F, Schulz RW, Bogerd J, Moreira RG, Furlan LR, Almeida EA, Maschio LR, Batlouni SR. Effects of re-stripping on the seminal characteristics of pacu (Piaractus mesopotamicus) during the breeding season. Gen. Comp. Endocrinol. 2016 Jan;225:162-173.

Shum EY, Jones SH, Shao A, Dumdie J, Krause MD, Chan WK, Lou CH, Espinoza JL, Song HW, Phan MH, Ramaiah M, Huang L, McCarrey JR, Peterson KJ, De Rooij DG, Cook-Andersen H, Wilkinson MF (2016). The antagonistic gene paralogs Upf3a and Upf3b govern nonsense-mediated RNA decay. Cell 165(2): 382-395. doi: 10.1016/j.cell.2016.02.046. PMID: 27040500

Song HW, Bettegowda A, Lake BB, Zhao AH, Skarbrevik D, Babajanian E, Sukhwani M, Shum EY, Phan MH, Plank TM, Richardson ME, Ramaiah M, Sridhar V, de Rooij DG, Orwig KE, Zhang K, Wilkinson MF (2016). The homeobox transcription factor RHOX10 drives mouse spermatogonial stem cell establishment. Cell Rep 17(1): 149-164. doi: 10.1016/j.celrep.2016.08.090. PMID: 27681428

Gómez-H L, Felipe-Medina N, Sánchez-Martín M, Davies OR, Ramos I, García-Tuñón I, de Rooij DG, Dereli I, Tóth A, Barbero JL, Benavente R, Llano E, Pendas AM (2016). C14ORF39/SIX6OS1 is a constituent of the synaptonemal complex and is essential for mouse fertility. Nat Commun 7:13298. doi: 10.1038/ncomms13298. PMID: 27796301

2015

Melo MC, van Dijk P, Andersson E, Nilsen TO, Fjelldal PG, Male R, Nijenhuis W, Bogerd J, de França LR, Taranger GL, Schulz RW. Androgens directly stimulate spermatogonial differentiation in juvenile Atlantic salmon (Salmo salar). Gen. Comp. Endocrinol. 2015 Jan; 211: 52-61

Nóbrega RH, de Souza Morais RD, Crespo D, de Waal PP, de França LR, Schulz RW, Bogerd J (2015) Fsh stimulates spermatogonial proliferation and differentiation in zebrafish via Igf3. Endocrinology 156, 3804-3817 PMID: 26207345.

2014

Melo M, Andersson E, Fjelldal PG, Bogerd J, Franca L, Taranger GL, Schulz RW. Salinity and photoperiod modulate pubertal development in Atlantic salmon (Salmo salar). J. Endocrinol. 2014 Feb; 220(3):319-335.

2013

Morais RD, Nóbrega RH, Gómez-González NE, Schmidt R, Bogerd J, França LR, Schulz RW. Thyroid hormone stimulates the proliferation of Sertoli cells and single type A spermatogonia in adult zebrafish (Danio rerio) testis. Endocrinology. 2013 Nov;154(11): 4365-76.

Andersson E, Schulz RW, Male R, Bogerd J, Patiña D, Benedet S, Norgberg B, Taranger GL. Pituitary gonadotropin and ovarian gonadotropin receptor transcript levels: Seasonal and photoperiod-induced changes in the reproductive physiology of female Atlantic salmon (Salmo salar). Gen. Comp. Endocrinol. 2013 Sep;191:247-58.

Baudiffier D, Hinfray N, Ravaud C, Creusot N, Chadili E, Porcher JM, Schulz RW, Brion F. Effect of in vivo chronic exposure to clotramizol on zebrafish testis function. Environ. Sci. Pollut. Res. Int. 2013 May;20(5): 2747-60.

Chen SX, Bogerd J, Schoonen NE, Martijn J, de Waal PP, Schulz RW. A progestin (17a,20b-dihydroxy-4-pregnen-3-one) stimulates early stages of spermatogenesis in zebrafish. Gen. Comp. Endocrinol. 2013 May;185:1-9.

Shao YT, Arvidsson M, Trombley S, Schulz RW, Schmitz M, Borg B. Androgen feedback effects on LH and FSH, and photoperiodic control of reproduction in male three-spined sticklebacks, Gasterosteus aculeatus. Gen. Comp. Endocrinol. 2013 Feb;182:16-23.

Hinfray N, Nóbrega RH, Caulier M, Baudiffier D, Maillot-Maréchal E, Chadili E, Palluel O, Porcher J-M, Schulz RW, Brion F. Cyp17a1 and Cyp19a1 in the zebrafish testis are differentially affected by œstradiol. J. Endocrinol. 2013 Feb;216(3):375-88.

2012

Good S, Yegorov S, Martijn J, Franck J, Bogerd J. New insights into ligand-receptor pairing and coevolution of relaxin family peptides and their receptors in teleosts. Int. J. Evol. Biol. 2012;2012:310278.

Chen SX, Almeida FFL, Andersson E, Taranger GL, Schmidt R, Schulz RW, Bogerd J. Cloning, pharmacological characterization and expression analysis of Atlantic cod (Gadus morhua, L.) nuclear progesterone receptor. Gen. Comp. Endocrinol. 2012 Oct;179(1):71-7.

Baudiffier D, Hinfray N, Vosges M, Creusot N, Chadili E, Porcher JM, Schulz RW, Brion F. A critical role of follicle-stimulating hormone (Fsh) in mediating the effect of clotrimazole on testicular steroidogenesis in adult zebrafish. Toxicology. 2012 Aug;298(1-3): 30-9.

Haugen T, Almeida FF, Andersson E, Bogerd J, Male R, Skaar KS, Schulz RW, Sørhus E, Wijgerde T, Taranger GL. Sex differentiation in Atlantic cod (Gadus morhua L.): morphological and gene expression studies. Reprod. Biol. Endocrinol. 2012 Jun;10:47 (http://www.rbej.com/content/10/1/47 ).

Schulz RW, van Dijk W, Chaves-Pozo E, García-López A, de Franca LR, Bogerd J. Sertoli cell proliferation in the adult testis is induced by unilateral gonadectomy in African catfish. Gen. Comp. Endocrinol. 2012 May;177(1):160-7.

Shao YT, Schulz RW, Borg B. Homeostasis of circulating androgens levels in the breeding male three-spined stickleback (Gasterosteus aculeatus). Zool. Sci. 2012; 51(8):1282-9.

2011

Hinfray N, Baudiffier D, Leal MC, Porcher JM, Aït-Aïssa S, Le Gac F, Schulz RW, Brion F. Characterization of testicular expression of P450 17α-hydroxylase, 17,20-lyase in zebrafish and its perturbation by the pharmaceutical fungicide clotrimazole. Gen. Comp. Endocrinol. 2011 Dec;174(3):309-17.

Skaar KS, Nóbrega RH, Magaraki A, Olsen LC, Schulz RW, Male R. Proteolytically activated, recombinant anti-mullerian hormone inhibits androgen secretion, proliferation, and differentiation of spermatogonia in adult zebrafish testis organ cultures. Endocrinology. 2011 Sep;152(9):3527-40.

de Almeida FF, Andersson E, Mittelholzer C, Karlsen O, Taranger GL, Schulz RW. Pituitary gonadotropin and testicular gonadotropin receptor expression in Atlantic cod (Gadusmorhua L.) during the first reproductive season: Effects of photoperiod modulation. Gen. Comp. Endocrinol. 2011 Aug 1;173(1):111-9.

Chen SX, Bogerd J, Andersson E, Almeida FF, Taranger GL, Schulz RW. Cloning, pharmacological characterization, and expression analysis of Atlantic salmon (Salmo salar L.) nuclear progesterone receptor. Reproduction. 2011 Apr;141(4):491-500.

2010

Nóbrega RH, Greebe CD, van de Kant H, Bogerd J, de França LR, Schulz RW. Spermatogonial stem cell niche and spermatogonial stem cell transplantation in zebrafish. PLoS One. 2010 Sep 20;5(9). pii: e12808.

Angelova K, de Jonge H, Granneman JC, Puett D, Bogerd J. Functional differences of invariant and highly conserved residues in the extracellular domain of the glycoprotein hormone receptors. J. Biol. Chem. 2010 Nov 5;285(45):34813-27.

García-López A, de Jonge H, Nóbrega RH, de Waal PP, van Dijk W, Hemrika W, Taranger GL, Bogerd J, Schulz RW. Studies in zebrafish reveal unusual cellular expression patterns of gonadotropin receptor messenger ribonucleic acids in the testis and unexpected functional differentiation of the gonadotropins. Endocrinology. 2010 May;151(5):2349-60.

Chen SX, Bogerd J, García-López A, de Jonge H, de Waal PP, Hong WS, Schulz RW. Molecular cloning and functional characterization of a zebrafish nuclear progesterone receptor. Biol. Reprod. 2010 Jan;82(1):171-81.

Levavi-Sivan B, Bogerd J, Mañanós EL, Gómez A, Lareyre JJ. Perspectives on fish gonadotropins and their receptors. Gen. Comp. Endocrinol. 2010 Feb 1;165(3):412-37.

Taranger GL, Carrillo M, Schulz RW, Fontaine P, Zanuy S, Felip A, Weltzien FA, Dufour S, Karlsen O, Norberg B, Andersson E, Hansen T. Control of puberty in farmed fish. Gen. Comp. Endocrinol. 2010 Feb 1;165(3):483-515.

Schulz RW, de França LR, Lareyre JJ, Le Gac F, Chiarini-Garcia H, Nobrega RH, Miura T. Spermatogenesis in fish. Gen. Comp. Endocrinol. 2010 Feb 1;165(3):390-411.

2009

Good-Avila SV, Yegorov S, Harron S, Bogerd J, Glen P, Ozon J, Wilson BC. Relaxin gene family in teleosts: phylogeny, syntenic mapping, selective constraint, and expression analysis. BMC Evol. Biol. 2009 Dec 16;9:293.

Andersson E, Nijenhuis W, Male R, Swanson P, Bogerd J, Taranger GL, Schulz RW. Pharmacological characterization, localization and quantification of expression of gonadotropin receptors in Atlantic salmon (Salmo salar L.) ovaries. Gen. Comp. Endocrinol. 2009 Sep 15;163(3):329-39.

de Waal PP, Leal MC, García-López A, Liarte S, de Jonge H, Hinfray N, Brion F, Schulz RW, Bogerd J. Oestrogen-induced androgen insufficiency results in a reduction of proliferation and differentiation of spermatogonia in the zebrafish testis. J. Endocrinol. 2009 Aug;202(2):287-97.

Leal MC, Cardoso ER, Nóbrega RH, Batlouni SR, Bogerd J, França LR, Schulz RW. Histological and stereological evaluation of zebrafish (Danio rerio) spermatogenesis with an emphasis on spermatogonial generations. Biol. Reprod. 2009 Jul;81(1):177-87.

Leal MC, de Waal PP, García-López A, Chen SX, Bogerd J, Schulz RW. Zebrafish primary testis tissue culture: an approach to study testis function ex vivo. Gen. Comp. Endocrinol. 2009 Jun;162(2):134-8.

Almeida FF, Taranger GL, Norberg B, Karlsen O, Bogerd J, Schulz RW. Photoperiod-modulated testis maturation in Atlantic cod (Gadus morhua, L.). Biol. Reprod. 2009 Apr;80(4):631-40.

García-López A, Bogerd J, Granneman JC, van Dijk W, Trant JM, Taranger GL, Schulz RW. Leydig cells express follicle-stimulating hormone receptors in African catfish. Endocrinology. 2009 Jan;150(1):357-65.

2008

de Waal PP, Wang DS, Nijenhuis WA, Schulz RW, Bogerd J. Functional characterization and expression analysis of the androgen receptor in zebrafish (Danio rerio) testis. Reproduction. 2008 Aug;136(2):225-34.

Vischer HF, Granneman JC, Koelink PJ, Marques RB, Bogerd J. Identification of a luteinizing hormone-selective determinant in the exodomain of a follicle-stimulating hormone receptor. Gen. Comp. Endocrinol. 2008 May 1;156(3):490-8.

van Bragt MP, Roepers-Gajadien HL, Korver CM, Bogerd J, Okuda A, Eggen BJ, de Rooij DG, van Pelt AM. Expression of the pluripotency marker UTF1 is restricted to a subpopulation of early A spermatogonia in rat testis. Reproduction. 2008 Jul;136(1):33-40.

Schulz RW, Liemburg M, García-López A, Dijk W, Bogerd J. Androgens modulate testicular androgen production in African catfish (Clarias gariepinus) depending on the stage of maturity and type of androgen. Gen. Comp. Endocrinol. 2008 Mar 1;156(1):154-63.

Leal MC, Feitsma H, Cuppen E, França LR, Schulz RW. Completion of meiosis in male zebrafish (Danio rerio) despite lack of DNA mismatch repair gene mlh1. Cell Tissue Res. 2008 Apr;332(1):133-9.

Almeida FF, Kristoffersen C, Taranger GL, Schulz RW. Spermatogenesis in Atlantic cod (Gadus morhua): a novel model of cystic germ cell development. Biol Reprod. 2008 Jan;78(1):27-34.

2007

Schulz RW, Bogerd J, Male R, Ball J, Fenske M, Olsen LC, Tyler CR. Estrogen-induced alterations in amh and dmrt1 expression signal for disruption in male sexual development in the zebrafish. Environ. Sci. Technol. 2007 Sep 1;41(17):6305-10.

Zmora N, Kazeto Y, Kumar RS, Schulz RW, Trant JM. Production of recombinant channel catfish (Ictalurus punctatus) FSH and LH in S2 Drosophila cell line and an indication of their different actions. J. Endocrinol. 2007 Aug;194(2):407-16.

Mizrak SC, Renault-Mihara F, Párraga M, Bogerd J, van de Kant HJ, López-Casas PP, Paz M, del Mazo J, de Rooij DG. Phosphoprotein enriched in astrocytes-15 is expressed in mouse testis and protects spermatocytes from apoptosis. Reproduction. 2007 Apr;133(4):743-51.

Feitsma H, Leal MC, Moens PB, Cuppen E, Schulz RW. Mlh1 deficiency in zebrafish results in male sterility and aneuploid as well as triploid progeny in females. Genetics. 2007 Apr;175(4):1561-9.

Bogerd J. Ligand-selective determinants in gonadotropin receptors. Mol. Cell. Endocrinol. 2007 Jan 2;260-262:144-52.

Dijkstra PD, Hekman R, Schulz RW, Groothuis TGG. Social stimulation, nuptial colouration, androgens and immunocompetence in a sexual dimorphic cichlid fish. Behav. Ecol. Sociobiol. 2007 Vol. 61, 599-609.

Rehbein H, Bogerd J. Identification of genetically modified zebrafish (Danio rerio) by protein- and DNA-analysis. Journal of Consumer Protection and Food Safety. 2007 Vol. 2, 122-125.

2006

Mizrak SC, Bogerd J, Lopez-Casas PP, Párraga M, Del Mazo J, de Rooij DG. Expression of stress inducible protein 1 (Stip1) in the mouse testis. Mol. Reprod. Dev. 2006 Nov;73(11):1361-6.

Vischer HF, Granneman JC, Bogerd J. Identification of follicle-stimulating hormone-selective beta-strands in the N-terminal hormone-binding exodomain of human gonadotropin receptors. Mol. Endocrinol. 2006 Aug;20(8):1880-93.

Navratil AM, Farmerie TA, Bogerd J, Nett TM, Clay CM. Differential impact of intracellular carboxyl terminal domains on lipid raft localization of the murine gonadotropin-releasing hormone receptor. Biol. Reprod. 2006 May;74(5):788-97.

Schulz RW, Andersson E, Taranger GL. Photoperiod manipulation can stimulate or inhibit pubertal testis maturation in Atlantic salmon (Salmo salar). Anim. Reprod. 2006 Vol. 3, 121-126.

2005

Bogerd J. Selective ligand-binding determinants in catfish and human gonadotropin receptors. Fish Physiol. Biochem. 2005 Apr;31(2-3):247-54.

Raghuveer K, Garhwal R, Wang DS, Bogerd J, Kirubagaran R, Rasheeda MK, Sreenivasulu G, Bhattachrya N, Tarangini S, Nagahama Y, Senthilkumaran B. Effect of methyl testosterone- and ethynyl estradiol-induced sex differentiation on catfish, Clarias gariepinus: expression profiles of DMRT1, Cytochrome P450 aromatases and 3 beta-hydroxysteroid dehydrogenase. Fish Physiol. Biochem. 2005 Apr;31(2-3):143-7.

Schulz RW, Menting S, Bogerd J, França LR, Vilela DA, Godinho HP. Sertoli cell proliferation in the adult testis—evidence from two fish species belonging to different orders. Biol. Reprod. 2005 Nov;73(5):891-8.

Bogerd J, Granneman JC, Schulz RW, Vischer HF. Fish FSH receptors bind LH: how to make the human FSH receptor to be more fishy? Gen. Comp. Endocrinol. 2005 May 15;142(1-2):34-43.

2004

Vischer HF, Marques RB, Granneman JC, Linskens MH, Schulz RW, Bogerd J. Receptor-selective determinants in catfish gonadotropin seat-belt loops. Mol. Cell. Endocrinol. 2004 Sep 30;224(1-2):55-63.

Blomenröhr M, Vischer HF, Bogerd J. Receptor mutagenesis strategies for examination of structure-function relationships. Methods Mol. Biol. 2004 Vol. 259:307-22.

Vogelaar CF, Hoekman MF, Brakkee JH, Bogerd J, Burbach JP. Developmental regulation of homeobox gene expression in dorsal root ganglion neurons is not recapitulated during regeneration of the crushed sciatic nerve. Neuroscience. 2004 Vol. 125(3):645-50.

2003

Vischer HF, Granneman JC, Linskens MH, Schulz RW, Bogerd J. Both recombinant African catfish LH and FSH are able to activate the African catfish FSH receptor. J. Mol. Endocrinol. 2003 Aug;31(1):133-40.

Vischer HF, Granneman JC, Bogerd J. Opposite contribution of two ligand-selective determinants in the N-terminal hormone-binding exodomain of human gonadotropin receptors. Mol. Endocrinol. 2003 Oct;17(10):1972-81.

Vischer HF, Bogerd J. Cloning and functional characterization of a testicular TSH receptor cDNA from the African catfish (Clarias gariepinus). J. Mol. Endocrinol. 2003 Apr;30(2):227-38.

Teves AC, Granneman JC, van Dijk W, Bogerd J. Cloning and expression of a functional estrogen receptor-alpha from African catfish (Clarias gariepinus) pituitary. J. Mol. Endocrinol. 2003 Apr;30(2):173-85.

Vischer HF, Teves AC, Ackermans JC, van Dijk W, Schulz RW, Bogerd J. Cloning and spatiotemporal expression of the follicle-stimulating hormone beta subunit complementary DNA in the African catfish (Clarias gariepinus). Biol. Reprod. 2003 Apr;68(4):1324-32.

Okuzawa K, Gen K, Bruysters M, Bogerd J, Gothilf Y, Zohar Y, Kagawa H. Seasonal variation of the three native gonadotropin-releasing hormone messenger ribonucleic acids levels in the brain of female red seabream. Gen. Comp. Endocrinol. 2003 Feb 15;130(3):324-32.

Vischer HF, Granneman JC, Noordam MJ, Mosselman S, Bogerd J. Ligand selectivity of gonadotropin receptors. Role of the beta-strands of extracellular leucine-rich repeats 3 and 6 of the human luteinizing hormone receptor. J. Biol. Chem. 2003 May 2;278(18):15505-13.

Vischer HF, Bogerd J. Cloning and functional characterization of a gonadal luteinizing hormone receptor complementary DNA from the African catfish (Clarias gariepinus). Biol. Reprod. 2003 Jan;68(1):262-71.

Schulz RW, van Dijk W, Bogerd J. Sertoli cell proliferation and FSH signalling in African catfish, Clarias gariepinus. Fish Physiol. Biochem. 2003 Vol. 28, 223-224.

Schulz RW. Endocrine regulation of spermatogenesis in teleost fish. Ann. Rev. Biomed. Sci. 2003 Vol. 5, 57-68.

2002

Blomenröhr M, Bogerd J, Leurs R, Goos H. Differences in structure-function relations between nonmammalian and mammalian GnRH receptors: what we have learnt from the African catfish GnRH receptor. Prog. Brain Res. 2002 Vol. 141:87-93.

Bogerd J, Diepenbroek WB, Hund E, van Oosterhout F, Teves AC, Leurs R, Blomenröhr M. Two gonadotropin-releasing hormone receptors in the African catfish: no differences in ligand selectivity, but differences in tissue distribution. Endocrinology. 2002 Dec;143(12):4673-82.

Lokman PM, Harris B, Kusakabe M, Kime DE, Schulz RW, Adachi S, Young G. 11-Oxygenated androgens in female teleosts: prevalence, abundance, and life history implications. Gen. Comp. Endocrinol. 2002 Oct 15;129(1):1-12.

Legler J, Zeinstra LM, Schuitemaker F, Lanser PH, Bogerd J, Brouwer A, Vethaak AD, De Voogt P, Murk AJ, Van der Burg B. Comparison of in vivo and in vitro reporter gene assays for short-term screening of estrogenic activity. Environ. Sci. Technol. 2002 Oct 15;36(20):4410-5.

Pfleger KD, Bogerd J, Millar RP. Conformational constraint of mammalian, chicken, and salmon GnRHs, but not GnRH II, enhances binding at mammalian and nonmammalian receptors: evidence for preconfiguration of GnRH II. Mol. Endocrinol. 2002 Sep;16(9):2155-62.

Consten D, Keuning ED, Bogerd J, Zandbergen MA, Lambert JG, Komen J, Goos HJ. Sex steroids and their involvement in the cortisol-induced inhibition of pubertal development in male common carp, Cyprinus carpio L. Biol. Reprod. 2002 Aug;67(2):465-72.

Rebers FE, Hassing GA, van Dijk W, van Straaten E, Goos HJ, Schulz RW. Gonadotropin-releasing hormone does not directly stimulate luteinizing hormone biosynthesis in male African catfish. Biol. Reprod. 2002 Jun;66(6):1604-11.

Blomenröhr M, ter Laak T, Kühne R, Beyermann M, Hund E, Bogerd J, Leurs R. Chimaeric gonadotropin-releasing hormone (GnRH) peptides with improved affinity for the catfish (Clarias gariepinus) GnRH receptor. Biochem J. 2002 Feb 1;361(Pt 3):515-23.

Garcia Hernandez MP, Garcia Ayala A, Agulleiro B, Garcia A, van Dijk W, Schulz RW. Development of a homologous radioimmunoassay for Mediterranean yellowtail (Seriola dumerilii, Risso 1810) LH. Aquaculture. 2002 Vol. 210, 203-218.

Viveiros ATM, Fessehaye Y, ter Veld M, Schulz RW, Komen J. Hand-stripping of semen and semen quality after maturational hormone treatments, in African catfish Clarias gariepinus. Aquaculture. 2002 Vol. 213, 373-386.

Schulz RW, Miura T. Spermatogenesis and its endocrine regulation. Fish Physiol. Biochem. 2002 Vol. 26, 43-56.

2001

Cavaco JE, Bogerd J, Goos H, Schulz RW. Testosterone inhibits 11-ketotestosterone-induced spermatogenesis in African catfish (Clarias gariepinus). Biol. Reprod. 2001 Dec;65(6):1807-12.

Wang L, Oh DY, Bogerd J, Choi HS, Ahn RS, Seong JY, Kwon HB. Inhibitory activity of alternative splice variants of the bullfrog GnRH receptor-3 on wild-type receptor signaling. Endocrinology. 2001 Sep;142(9):4015-25.

Dubois EA, Zandbergen MA, Peute J, Bogerd J, Goos HJ. Development of three distinct GnRH neuron populations expressing two different GnRH forms in the brain of the African catfish (Clarias gariepinus). J. Comp. Neurol. 2001 Aug 27;437(3):308-20.

Blomenröhr M, Kühne R, Hund E, Leurs R, Bogerd J, ter Laak T. Proper receptor signalling in a mutant catfish gonadotropin-releasing hormone receptor lacking the highly conserved Asp(90) residue. FEBS Lett. 2001 Jul 20;501(2-3):131-4.

Schulz RW, Vischer HF, Cavaco JE, Santos EM, Tyler CR, Goos HJ, Bogerd J. Gonadotropins, their receptors, and the regulation of testicular functions in fish. Comp. Biochem. Physiol. B. Biochem. Mol. Biol. 2001 Jun;129(2-3):407-17.

Bogerd J, Blomenröhr M, Andersson E, van der Putten HH, Tensen CP, Vischer HF, Granneman JC, Janssen-Dommerholt C, Goos HJ, Schulz RW. Discrepancy between molecular structure and ligand selectivity of a testicular follicle-stimulating hormone receptor of the African catfish (Clarias gariepinus). Biol. Reprod. 2001 Jun;64(6):1633-43.

Cavaco JE, van Baal J, van Dijk W, Hassing GA, Goos HJ, Schulz RW. Steroid hormones stimulate gonadotrophs in juvenile male African catfish (Clarias gariepinus). Biol. Reprod. 2001 May;64(5):1358-65.

Consten D, Bogerd J, Komen J, Lambert JG, Goos HJ. Long-term cortisol treatment inhibits pubertal development in male common carp, Cyprinus carpio L. Biol. Reprod. 2001 Apr;64(4):1063-71.

Bosma PT, Blázquez M, Fraser EJ, Schulz RW, Docherty K, Trudeau VL. Sex steroid regulation of glutamate decarboxylase mRNA expression in goldfish brain is sexually dimorphic. J. Neurochem. 2001 Feb;76(4):945-56.

Wang L, Yoo MS, Kang HM, Im WB, Choi HS, Bogerd J, Kwon HB. Cloning and characterization of cDNAs encoding the GnRH1 and GnRH2 precursors from bullfrog (Rana catesbeiana). J. Exp. Zool. 2001 Feb 15;289(3):190-201.

Wang L, Bogerd J, Choi HS, Seong JY, Soh JM, Chun SY, Blomenröhr M, Troskie BE, Millar RP, Yu WH, McCann SM, Kwon HB. Three distinct types of GnRH receptor characterized in the bullfrog. Proc. Natl. Acad. Sci. USA. 2001 Jan 2;98(1):361-6.

Mikolajczyk T, Roelants I, Epler R, Ollevier F, Schulz RW, Sokolowska-Mikolajczyk M, Breton B. Assessment of tissue damaging effects of mixed micellar absorption enhancers on the intestinal mucosa of common carp (Cyprinus carpio), African catfish (Clarias gariepinus) and rainbow trout (Oncorhynchus mykiss) as a consequence of enhanced intestinal absorption of sGnRH-a. J. Appl. Ichthyol. 2001 Vol. 17, 267-272.