Fifth international symposium on the biology of vertebrate sex determination is going to be held at Royal Kona Resort in Kona, Hawaii from April 20 through April 24, 2009. The aim of this symposium is to bring together scientists and students from a wide variety of disciplines with a common interest in sex determination. I am also participating at the meeting and the title is "Neurotrophin-3, a target gene for Sry action". I anticipate meeting with renown scientists in the field. So far, in each symposium, scientists have presented at least one breakthrough in the field. I am anxiously waiting to hear another yet new breakthrough  on Sry/Sox9 signalling in the gonad. For details of this and previous meetings, please visit the following website:

Symposium website

Photogallery 2006

With Drs. Eva Eicher and Roger V. Short.

Onset of meiosis in the chicken embryo; evidence of a role for retinoic acid. 
Smith CA, Roeszler KN, Bowles J, Koopman P, Sinclair AH. 
BMC Dev Biol. 2008 Sep 17; 8:85

Meiosis in higher vertebrates shows a dramatic sexual dimorphism: germ cells enter meiosis and arrest at prophase I during embryogenesis in females, whereas in males they enter mitotic arrest during embryogenesis and enter meiosis only after birth. Here we report the molecular analysis of meiosis onset in the chicken model and provide evidence for conserved regulation by retinoic acid. RESULTS: Meiosis in the chicken embryo is initiated late in embryogenesis (day 15.5), relative to gonadal sex differentiation (from day 6). Meiotic germ cells are first detectable only in female gonads from day 15.5, correlating with the expression of the meiosis marker, SCP3. Gonads isolated from day 10.5 female embryos and grown in serum-free medium could still initiate meiosis at day 16.5, suggesting that this process is controlled by an endogenous clock in the germ cells themselves, and/or that germ cells are already committed to meiosis at the time of explantation. Early commitment is supported by the analysis of chicken STRA8, a pre-meiotic marker shown to be essential for meiosis in mouse. Chicken STRA8 is expressed female-specifically from embryonic day 12.5, preceding morphological evidence of meiosis at day 15.5. Previous studies have shown that, in the mouse embryo, female-specific induction of STRA8 and meiosis are triggered by retinoic acid. A comprehensive analysis of genes regulating retinoic acid metabolism in chicken embryos reveals dynamic expression in the gonads. In particular, the retinoic acid-synthesising enzyme, RALDH2, is expressed in the left ovarian cortex at the time of STRA8 up-regulation, prior to meiosis. CONCLUSION: This study presents the first molecular analysis of meiosis onset in an avian embryo. Although aspects of avian meiosis differ from that of mammals, a role for retinoic acid may be conserved.

Article link: http://www.biomedcentral.com/1471-213X/8/85

Sex reversal of the amphibian, Xenopus tropicalis, following larval exposure to an aromatase inhibitor.
Olmstead AW, Kosian PA, Korte JJ, Holcombe GW, Woodis KK, Degitz SJ. 
Aquat Toxicol. 2008 Aug 15. [Epub ahead of print] 

U.S. Environmental Protection Agency, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, 6201 Congdon Boulevard, Duluth, MN, United States.

Aromatase is a steroidogenic enzyme that catalyzes the conversion of androgens to estrogens in vertebrates. Modulation of this enzyme's activity by xenobiotic exposure has been shown to adversely affect gonad differentiation in a number of diverse species. We hypothesized that exposure to the aromatase inhibitor, fadrozole, during the larval development of the tropical clawed frog, Xenopus tropicalis, would result in masculinization of the developing female gonad. Tadpoles were exposed to fadrozole at nominal concentrations from 1 to 64mug/L in a flow-through system from <24h post-fertilization (Nieuwkoop Faber (NF) stage 15-20) to metamorphosis (NF stage 66). At metamorphosis, morphologically examined gonads indicated complete masculinization of all tadpoles at concentrations of 16mug/L and above and a significant bias in sex ratio towards males at concentrations of 1mug/L and above. No effects on time to metamorphosis, body mass, or body length were observed. A random subsample of frogs was raised to reproductive maturity (39 weeks post-fertilization) in control water. All frogs exposed as tadpoles to 16mug/L fadrozole or greater possessed testes at sexual maturity. Intersexed gonads characterized by the presence of both testicular and ovarian tissue were observed in 12% of frogs in the 4mug/L treatment. No differences in estradiol, testosterone, or vitellogenin plasma concentrations were observed in exposed males or females compared to controls. Females in the 4mug/L treatment possessed a significantly greater percentage of pre-vitellogenic oocytes than controls and were significantly smaller in body mass. No differences in sperm counts were observed in exposed males compared to controls. Results from this study demonstrate that larval exposure to an aromatase inhibitor can result in the complete masculinization of female gonads. These masculinized females are phenotypically indistinguishable from normal males at adulthood. Lower levels of aromatase inhibition resulted in intersexed gonads and possible female reproductive impairment at adulthood. These results indicate that exposure of amphibians to xenobiotics capable of inhibiting aromatase would result in adverse reproductive consequences.

Article link: http://www.ncbi.nlm.nih.gov/pubmed/18804292

Germ line control of female sex determination in zebrafish. 
Siegfried KR, Nüsslein-Volhard C. 
Dev Biol. 2008 Oct 7. [Epub ahead of print]

A major transition during development of the gonad is commitment from an undifferentiated "bi-potential" state to ovary or testis fate. In mammals, the oogonia of the developing ovary are known to be important for folliculogenesis. An additional role in promoting ovary fate or female sex determination has been suggested, however it remains unclear how the germ line might regulate this process. Here we show that the germ line is required for the ovary versus testis fate choice in zebrafish. When the germ line is absent, the gonad adopts testis fate. These germ line deficient testes have normal somatic structures indicating that the germ line influences fate determination of surrounding somatic tissues. In germ line deficient animals the expression of the ovary specific gene cyp19a1a fails to be maintained whereas the testis genes sox9a and amh remain expressed. Furthermore, we observed decreased levels of the ovary specific genes cyp19a1a and foxL2 in germ line deficient animals prior to morphological sex differentiation of the gonad. We propose that the germ line has a common role in female sex determination in fish and mammals. Additionally, we show that testis specification is sufficient for masculinization of the fish pointing to a direct role of hormone signaling from the gonad in directing sex differentiation of non-gonadal tissues.

Article link: http://www.ncbi.nlm.nih.gov/pubmed/18930041

A group of scientists in the University of the Ryukyus, Japan have shown that male wrasses, which do never change sex in their life, have potential to change sex. A brief estrogen treatment can cause those males to change into female. This finding cracks the code of sexual plasticity in wrasses and raises scientist`s eyebrows on developmental plasticity of lower vertebrates. Can other gonochoristic fish, such as salmon, trout, catfish, tilapias, etc. can change sex with such an exposure? Does a life-long exposure to such chemicals cause sex reversal in these species in a long run? Such issues are important in the current scenario of global environmental awareness.

Sex steroids are considered major regulators of sex change processes in fish. Estrogen depletion is shown to be crucial for female-male sex change initiation; however, its role in male-female sex change is largely unknown. In the present study, we examined the effects of estradiol-17beta (E2) treatments on testes of initial-phase (IP) males of the three-spot wrasse (Halichoeres trimaculatus), which naturally do not undergo male-female sex change. Sexually mature IP males were fed a diet containing E2 (low, 20 ug/g feed; high, 200 ug/g feed) for 6 or 12 weeks, and changes in gonadal structures were examined. Percentage of sex change varied with the dosage of E2 and the duration of treatment. All individuals treated with high-dose E2 for 6 weeks had ovaries with many immature oocytes; whereas 75% of individuals treated with low-dose of E2 for 6 weeks and sampled on the 12th week had ovaries with yolky oocytes and an ovarian cavity indicating a typical mature ovary. No testicular tissue was observed in sex-reversed gonads in both treatment groups. Contrary to the previous assumptions, present results suggest that IP male wrasses have the potential to undergo male-female sex change in response to exogenous estrogen. How the presence or absence of estrogen creates sexual plasticity in gonadal germ and somatic cells remains to be clarified.

FW: Symposium Announcement

Official website of the Symposium



Dear Colleagues:
Professor Yoshitaka Nagahama officially retires from his position at the National Institute for Basic Biology in March 2008. To honor and celebrate Professor Nagahama’s extensive contributions to the field of fish reproduction, we invite you to join us in Honolulu, Hawaii, May 30-June 1, 2008, to participate in an international symposium entitled "Sex Determination and Gametogenesis in Fish: Current Status and Future Challenges".
This symposium will highlight advances in the field of fish reproduction. Reflecting Professor Nagahama’s research interests, the symposium will be composed of two sessions, one focused on sex determination and differentiation (May 31), and one on germ cell biology and gametogenesis (June 1). Each session will have three or more eminent state-of-the-art speakers invited by the Organizing Committee, and contributed papers on fundamental and applied aspects of each area. One poster session will also be scheduled.
The symposium will be held on the University of Hawaii’s Honolulu campus in close proximity to the hotels and beaches of Waikiki. An opening social the evening of May 30, a banquet, and an excursion during one of the afternoons are planned. We expect that abstracts and registration will be due in early February.
The Symposium will be held directly after the First World Congress on Reproductive Biology and the Annual Meeting of the Society for the Study of Reproduction, which are being held in Kona, Hawaii May 25-30. Information on these meetings is available at http://www.ssr.org/
To facilitate planning, please respond to this invitation by January 7, 2008 if you intend to participate. Please email the following information to Graham Young (GrahamY@u.washington.edu):

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Name:
Institution:
Address:
Phone:
FAX:
Email:
I would like to present an oral communication: Yes / No. Or Attend Only
Tentative title:
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Further information on the scientific program, registration, details of abstract submission and hotel information will be available within the next month.
We hope that you will be able to join us in Hawaii to honor Professor Nagahama.

Sincerely,
International Organizing Committee
Gordon Grau
Hirohiko Kagawa
Penny Swanson
Graham Young 

Local Organizing Committee in Japan
Shinji Adachi
Kataaki Okubo
Michiyasu Yoshikuni

Dr. Md. Saydur Rahman, a Postdoctoral Research Associate at Marine Science Institute of University of Texas -Austin (Port Aransas), is a good friend of mine. By profession, he is a  Fish Physiologist. He says "Coastal waters have low level of dissolved oxygen (condition of hypoxia) throughout the world over the past few decades, as a result of increased run-off from human agricultural and industrial activities". His research focuses on how hypoxia affects growth and physiology of marine fishes.  Recently, his team reported that fish inhabiting these coastal waters had little ovarian and testicular growth, low egg and sperm production, and low levels of reproductive hormones during the time when they would normally be increasing in preparation for reproduction. Laboratory studies showed that hypoxia caused endocrine disruption through decreasing levels of serotonin in the brain. If such a situation persists, it will affect the entire population of fish and other coastal organisms, and ultimately the marine ecosystem as a whole. 
His major publications 
Other publication links
Marine Science Institute 

Germ cells are essential for sexual dimorphism in the medaka gonad.
Kurokawa H, Saito D, Nakamura S, Katoh-Fukui Y, Ohta K, Baba T, Morohashi K, Tanaka M. Proc Natl Acad Sci U S A.104:16958-16963 (2007).

To further elucidate the roles of germ cells in the sex differentiation of gonads, we have used the medaka, a teleost fish, to generate mutants that lack germ cells from the onset of gonadogenesis by the morpholino-mediated knockdown of cxcr4. The resulting germ-cell-deficient medaka show female-to-male sex reversal of their secondary sex characteristics, accompanied by increased levels of androgen and reduced levels of estrogen. A failure to maintain granulosa cells or estrogen-producing cells also occurs at early stages of sex differentiation in the cxcr4 morphants, before the initiation of gonadal morphogenesis. In contrast, androgen-producing cells are unaffected in germ-cell-deficient medaka of either sex. In addition, a single tube-like gonad that expresses male-specific genes is formed in these mutants irrespective of the genetic sex. Significantly, each of these mutant phenotypes occurs in a somatic cell-autonomous manner, suggesting that gonadal somatic cells are predisposed toward male development in the absence of germ cells. This highlights the importance of germ cells in the sexual dimorphism of the gonads.

Article Link: http://www.pnas.org/cgi/content/full/104/43/16958