Female Secondary Sexual Characteristics Research Articles

Ultrahigh-Sensitivity Detection of 17β-Estradiol

17β-estradiol (E2), a vital female sex hormone, plays a crucial role in female reproductive cycles and secondary sexual characteristics. The quantification of E2 concentration in human blood and urine samples is essential because a deviation from physiological levels of E2 indicates the development of diseases and abnormalities such as precocious puberty, breast cancer, weight gain, abnormal menstruation, osteoporosis, and infertility. In addition, the detection of E2 in food and the environment has gained widespread interest because of its role as an endocrine disruptor (environmental hormone) that can perturb physiological processes. E2 is used as a drug for hormone therapy. Various E2 detection technologies for diagnosing relevant human diseases, drug screening, and environmental monitoring have been demonstrated in studies. In this article, we have reviewed technological strategies developed for E2 detection with ultrahigh sensitivity, with a limit of detection comparable to several pg/mL or lower. We observed that gold nanoparticles (AuNPs) were used as nanoplatforms for signal amplification, which enabled ultrahigh sensitivity in most studies. Signal amplification was facilitated by AuNP characteristics such as the versatility of surface biochemistry, exceedingly large surface-to-volume ratio, surface plasmonic activity, luminescence quenching ability, and biocompatibility. These techniques have been used to detect E2 in food, water, human serum, and urine with ultrahigh sensitivity. We summarize the working principles of E2 detection strategies that allow ultrahigh sensitivity and provide an approach for future work required for the elucidation of practical applications of these technologies.

The prevailing social stigma around disorders of sexual development in developing countries

Disorders of sexual development (DSD), apart from medical disease, is a psychosocial stigma to not only the patient but also their whole family. We present the case of a 24-year-old 46XX, raised as male, with ambiguous genitalia and cyclical hematuria with normal female internal genitalia and secondary sexual characteristics. This case underscores the influence of social stigma and the psychosocial vulnerability associated with DSD on individuals’ lives in developing countries.

Genetic evidence for differential functions of figla and nobox in zebrafish ovarian differentiation and folliculogenesis

FIGLA and NOBOX are important oocyte-specific transcription factors. Both figla-/- and nobox-/- mutants showed all-male phenotype in zebrafish due to increased dominance of the male-promoting pathway. The early diversion towards males in these mutants has precluded analysis of their roles in folliculogenesis. In this study, we attenuated the male-promoting pathway by deleting dmrt1, a key male-promoting gene, in figla-/- and nobox-/- fish, which allows a sufficient display of defects in folliculogenesis. Germ cells in figla-/-;dmrt1-/- double mutant remained in cysts without forming follicles. In contrast, follicles could form well but exhibited deficient growth in nobox-/-;dmrt1-/- double mutants. Follicles in nobox-/-;dmrt1-/- ovary could progress to previtellogenic (PV) stage but failed to enter vitellogenic growth. Such arrest at PV stage suggested a possible deficiency in estrogen signaling. This was supported by lines of evidence in nobox-/-;dmrt1-/-, including reduced expression of ovarian aromatase (cyp19a1a) and level of serum estradiol (E2), regressed genital papilla (female secondary sex characteristics), and more importantly the resumption of vitellogenic growth by E2 treatment. Expression analysis suggested Nobox might regulate cyp19a1a by controlling Gdf9 and/or Bmp15. Our discoveries indicate that Figla is essential for ovarian differentiation and follicle formation whereas Nobox is important for driving subsequent follicle development.

Subtunical Reduction Clitoroplasty of a 22 years old Female for Clitoromegaly with Congenital Adrenal Hyperplasia-Case Report

Clitoromegaly is an abnormal condition commonly related to congenital adrenal hyperplasia. We presented a 22 years old adult female patient with chief complaint of enlarged clitoris since birth, other female secondary sexual characteristics were normal. The karyotype test result was 46 XX. Subtunical resection of erectile cavernous tissue of the enlarged clitoris with preservation of intact blood supply to the glans is a safe method of diminishing shaft and glans size and allow the patient to do sexual activity after marriage during a two-years follow up. Bangabandhu Sheikh Mujib Med. Coll. J. 2023;2(2):127-130.

FRI453 Genetic Heterogeneity of Hypothalamic Hypogonadism DIsorders

Abstract Disclosure: C. Bheeman: None. O. Astapova: None. Title: Genetic Heterogeneity of Hypothalamic Hypogonadism disorders. Introduction: Hypothalamic hypogonadism (HH) can be defined as having inappropriately low serum concentrations of gonadotropins in the presence of low circulating concentrations of sex steroids. It represents a group of genetically and clinically heterogeneous disorders. Case A 32-year-old female who presented to the endocrine clinic for evaluation of infertility. Patient had menarche at age 12 but became amenorrhoeic at age 14. Her physical exam was notable for normal female secondary sexual characteristics and intact sense of smell. She had no history of bone fracture or menopausal symptoms. The patient had failed the progesterone withdrawal test twice, but had withdrawal bleeding with the birth control pill or with hormonal replacement therapy. She had failed ovulation induction with clomiphene citrate, but was able to conceive 3 pregnancies through in vitro fertilization. Patient’s labs off of hormonal replacement and birth control were: LH <0.3. FSH 0.6, Estradiol <5, Progesterone 0.4. Her prolactin level was within normal limits at 6.6 and her TSH was 1.08. MRI of the brain showed no abnormalities in the pituitary gland. Genetic testing showed that the patient was heterozygous for a duplication mutation in the ANOS1 gene. Conclusion The genotypic and phenotypic heterogeneity that can be seen in HH disorders is due to the numerous genes involved in hypothalamic hypogonadism and their intricate interactions. Mutations contributing to HH can be involved in either the neurodevelopmental or neuroendocrine pathways of the hypothalamic pituitary gonadal axis or in both. There are mutations that can be inactivating variants while some can play the role of the modifier genes. The later may be able to explain the incomplete penetrance and variable expressivity sometimes seen in HH. It is important to note that though > 60 genes have been implicated in HH 50% of the cases remain genetically undiagnosed. This case is particularly interesting as this patient is a female with a heterozygous mutation on the ANOS1 gene, the primary gene associated with Kallmann syndrome. Kallmann syndrome is a X-linked recessive disorder and therefore the patient having phenotypical expression of the mutation is unexpected. Through the presentation of this case we aim to explore different modes of genetic expression and the different mechanisms that could have led to this patient hypothalamic hypogonadism. Presentation Date: Friday, June 16, 2023

Androgen insensitivity syndrome: a review.

Androgen insensitivity syndrome (AIS) is a disorder characterized by peripheral androgen resistance due to androgen receptor mutations in subjects with 46 XY karyotype. The severity of hormone resistance (complete, partial or mild) determines the wide spectrum of phenotypes. We performed a literature review on Pubmed focusing on etiopathogenesis, molecular alterations, and diagnostic-therapeutic management. AIS is determined by a large variety of X-linked mutations that account for the wide phenotypic spectrum of subjects; it represents one of the most frequent disorders of sexual development (DSD). Clinical suspicion can arise at birth in partial AIS, due to the presence of variable degrees of ambiguity of the external genitalia, and at pubertal age in complete AIS, due to the development of female secondary sex characteristics, primary amenorrhea, and absence of female primary sex characteristics (uterus and ovaries). Laboratory tests showing elevated LH and testosterone levels despite mild or absent virilization may be helpful, but diagnosis can be achieved only after genetic testing (karyotype examination and androgen receptor sequencing). The clinical phenotype and especially the decision on sex assignment of the patient, if the diagnosis is made at birth or in the neonatal period, will guide the following medical, surgical and psychological management. For the management of AIS, a multidisciplinary team consisting of physicians, surgeons, and psychologists is highly recommended to support the patient and his/her family on gender identity choices and subsequent appropriate therapeutic decisions.

Ovariectomy in mice primes hippocampal microglia to exacerbate behavioral sickness responses

Estrogens are a group of steroid hormones that promote the development and maintenance of the female reproductive system and secondary sex characteristics. Estrogens also modulate immune responses; estrogen loss at menopause increases the risk of inflammatory disorders. Elevated inflammatory responses in the brain can lead to affective behavioral changes, which are characteristic of menopause. Thus, here we examined whether loss of estrogens sensitizes microglia, the primary innate immune cell of the brain, leading to changes in affective behaviors. To test this question, adult C57BL/6 mice underwent an ovariectomy to remove endogenous estrogens and then received estradiol hormone replacement or vehicle. After a one-month recovery, mice received an immune challenge with lipopolysaccharide (LPS) or vehicle control treatment and underwent behavioral testing. Ovariectomized, saline-treated mice exhibited reduced social investigation compared to sham-operated mice. Furthermore, ovariectomized mice that received LPS exhibited an exacerbated decrease in sucrose preference, which was ameliorated by estradiol replacement. These results indicate that ovariectomy modulates affective behaviors at baseline and in response to an inflammatory challenge. Ovariectomy-related behavioral changes were associated with downregulation of Cx3cr1, a microglial receptor that limits activation, suggesting that estrogen loss can disinhibit microglia to immune stimuli. Indeed, estradiol treatment reduced ovariectomy-induced increases in Il1b and Il6 expression after an immune challenge. Changes in microglial reactivity following ovariectomy are likely subtle, as overt changes in microglial morphology (e.g., soma size and branching) were limited. Collectively, these results suggest that a lack of estrogens may allow microglia to confer exaggerated neuroimmune responses, thereby raising vulnerability to adverse affective- and sickness-related behavioral changes.

A single-cell transcriptomic atlas characterizes cell types and their molecular features in yak ovarian cortex.

The ovary as one of the most dynamic organs produces steroids to orchestrate female secondary sexual characteristics, harbors ovarian reserve for oocytes, releases mature oocytes for fertilization, and maintains pregnancy. Yak (Bos grunniens) is the only bovid animal that can adapt to the harsh climatic conditions on the Qinghai-Tibetan Plateau (altitudes of over 3000 m above sea level). However, the cellular atlas is composed of oocytes and other somatic cells, and their individual molecular characteristics remain to be elucidated in the yak ovary. Here, single-cell RNA sequencing (scRNA-seq) was performed to delineate the molecular signature of various cell types in the yak ovarian cortex. A cellular atlas of yak ovarian cortex was constructed successfully on the basis of the differentially expressed genes (DEGs) from the distinct cell types and their functional enrichment analysis, comprising endothelial cells, nature kill cells, stromal cells, smooth muscle cells, oocytes, macrophages, epithelial cells, and granulosa cells. Meanwhile, the signature genes were determined based on their expression specificity in each cell type. A cell-to-cell communication network was built in light of the differentially overexpressed ligand and receptor genes from each cell type. Further, the oocytes were subdivided into four subtypes based on their individual DEGs and the functional enrichment of the DEGs. FST and TOP2A were identified as maker genes for oocytes by immunostaining in the yak ovarian cortex. The cellular atlas reveals the biological characteristics of the ovarian cortex at the cellular molecular level and provides insights into female reproductive biology via cellular communications in the yak.

Level of Estrogen in Females-The Different Impacts at Different Life Stages.

Historically, a high level of estrogen in women is regarded as the signature for a longer lifespan than men. Estrogen is known to be responsible for the development and regulation of the female reproductive system and secondary sex characteristics. Ovariectomy brings on numerous complications such as early menopause, heart disease, and osteoporosis. Thus, ovariectomy impacts the long-term health and lifespan of women. However, the level of estrogen at different life stages should be managed differently. Life quality can be measured in many ways, but mainly it relates to how an individual is doing in terms of being healthy, comfortable, and able to participate in or enjoy life experiences. First of all, ovariectomy not only reduces the level of estrogen but also destroys the reproductive metabolism and potentially other metabolism functions; it may also reduce the lifespan because of the overall impact, not necessary due to the low level of estrogen. Secondly, according to the principal law of the lifespan (PLOSP), the impacts of ovariectomy at different life stages will be different. The objective of this article is to provide readers with a new view of the research on estrogen. Based on the PLOSP, we recapture the estrogen levels at different life stages and explore potential alternative approaches to the manipulation of the levels of estrogen based on the biological features of the difference life stages. Thus, a low level of estrogen in the early life stage may make a woman live longer than a woman with a normal level of estrogen. However, a low estrogen level does not equal ovariectomy. Here, we explain the different impacts of the estrogen levels during different life stages; the effects on the lifespan of the manipulation of estrogen levels at different life stages; and the differences among the estrogen levels, ovariectomy effects, life stages, and lifespan. The personalized manipulation of estrogen levels and relevant growth factors according to the characterization of the life stages may be able to extend the heathy lifespan of women.

Management challenges of disorders of sex development- Case Series


 
 
 INTRODUCTION: Disorders of sex development (DSDs) are genetic abnormalities characterized by discordance between phenotypic, gonadal, and genetic sex. They are grouped into two categories based on karyotype: 46, XX DSD and 46, XY DSD.CASES: We reviewed two patients referred to the Rwanda Military Hospital genetic unit. The first patient was a 3-year-old toddler who was referred for confusing sex organs. Physical examination showed ambiguous genital organs with hypospadias and micropenis. Pelvic examination showed a swelling solid mass hat leading to a suspicion of ovary or undescended testes or combined ovary and testes (ovotestes). The second patient was a 17 years old teenager who presented with primary amenorrhea and lack of female secondary sexual characteristics at her age. The karyotype test was performed to investigate the genotypic sex of the patients and results revealed the karyotype formula of 46, XX/XY indicating the presence of two cell lines in the patient for the toddler and 46XYinv9 (p11q13) indicating the mismatch between the genotype and phenotype of the patients for the teenager.
 CONCLUSION: Patients were diagnosed with Disorder of Sex Development with 46, XX/XY and 46, XY genotypes respectively. A multidisciplinary team of a geneticist, urologist, endocrinologist and a psychologist reviewed the patient for the effective management.
 
 

Chemical synthesis and functional evaluation of the crayfish insulin-like androgenic gland factor

Insulin-like androgenic gland factor (IAG) from the marbled crayfish Procambarus virginalis is an insulin-like heterodimeric peptide composed of A and B chains and has an Asn-linked glycan at the B chain. IAG is considered to be a male sex hormone inducing the sex differentiation to male in decapod crustacean, although there is no report on the function of IAG peptide in vivo. In order to characterize P. virginalis IAG, we chemically synthesized it and evaluated its biological function in vivo. A and B chains were prepared by the ordinary solid-phase peptide synthesis, and three disulfide bonds were formed regioselectively by dimethyl sulfoxide oxidation, pyridylsulfenyl-directed thiolysis and iodine oxidation reactions. An IAG disulfide isomer was also prepared by the same manner. Circular dichroism spectral analysis revealed that the disulfide bond arrangement affected the peptide conformation, which was similar to the other insulin-family peptides analyzed so far. On the other hand, the glycan moiety attached at the B chain had no effect on the peptide secondary structure. Injection of the synthetic IAG and its disulfide isomer to female crayfish did not induce male characteristics on the external morphology, but both peptides suppressed the oocyte maturation in vivo. These results suggest that IAG has a pivotal role on the suppression of female secondary sex characteristics.

Clinical characteristics and molecular genetics of complete androgen insensitivity syndrome patients: a series study of 30 cases from a Chinese tertiary medical center

To study the clinical characteristics and genetic basis of complete androgen insensitivity syndrome (CAIS) in patients from the People's Republic of China. CAIS patients with 46 XY karyotype produce male levels of androgens but present with female external genitalia and secondary sex characteristics. The majority of affected individuals have androgen receptor (AR) gene mutations. This case series explored clinical and molecular characteristics of CAIS patients from the People's Republic of China. Genomic DNA from peripheral blood of clinically diagnosed CAIS patients was sequenced for mutation in the androgen receptor (AR) gene and steroid 5α-reductase type 2 gene (SRD5A2). Participants were recruited from Peking Union Medical College Hospital when they came in for consultation. Thirty patients from unrelated families were recruited. Data from medical documents recording diagnosis and treatment of these patients were retrospectively collected. Patient genotypes were determined by sequencing the AR and SRD5A2 genes. Their clinical characteristics were summarized based on symptoms, hormone profiles, operative findings, and pathological results. Twenty-one patients diagnosed with CAIS had mutations in AR exons. Analysis of AR exons revealed the presence of seven novel mutations (c.58C>T, c.645_652delGGGGGCTC, c.910G>T, c.1078C>T, c.1786T>A, c.2230G>T, and c.2522G>C); of these mutations, 47.6% (10/21) were located in the ligand-binding domain. Gonadal insufficiency was found in one case of CAIS. Among the remaining nine patients, three had SRD5A2 mutations and therefore a steroid 5α-reductase deficiency. No AR or SRD5A2 mutations were detected in the other six patients. This study broadens the spectrum of known AR gene mutations responsible for CAIS, and implies that there can be more complex underlying causes of CAIS.

11β-Hydroxylase loss disrupts steroidogenesis and reproductive function in zebrafish.

The roles of androgens in male reproductive development and function in zebrafish are poorly understood. To investigate this topic, we employed CRISPR/Cas9 to generate cyp11c1 (11β-hydroxylase) mutant zebrafish lines. Our study confirms recently published findings from a different cyp11c1-/- mutant zebrafish line, and also reports novel aspects of the phenotype caused by loss of Cyp11c1 function. We report that Cyp11c1-deficient zebrafish display predominantly female secondary sex characteristics, but may possess either ovaries or testes. Moreover, we observed that cyp11c1-/- mutant male zebrafish are profoundly androgen- and cortisol-deficient. These results provide further evidence that androgens are dispensable for testis formation in zebrafish, as has been demonstrated previously in androgen-deficient and androgen-resistant zebrafish. Herein, we show that the testes of cyp11c1-/- mutant zebrafish exhibit a disorganised tubular structure; and for the first time demonstrate that the spermatic ducts, which connect the testes to the urogenital orifice, are severely hypoplastic in androgen-deficient zebrafish. Furthermore, we show that spermatogenesis and characteristic breeding behaviours are impaired in cyp11c1-/- mutant zebrafish. Expression of nanos2, a type A spermatogonia marker, was significantly increased in the testes of Cyp11c1-deficient zebrafish, whereas expression of markers for later stages of spermatogenesis was significantly decreased. These observations indicate that in zebrafish, production of type A spermatogonia is androgen-independent, but differentiation of type A spermatogonia is an androgen-dependent process. Overall, our results demonstrate that whilst androgens are not required for testis formation, they play important roles in determining secondary sexual characteristics, proper organisation of seminiferous tubules, and differentiation of male germ cells.

Good vibrations: a novel method for sexing turtles

The ability to accurately determine the sex of individuals is important for research and conservation efforts. While most species of turtle exhibit secondary sexual dimorphisms that can be used to reliably infer sex, there are some species that are very difficult to sex, and even within many dimorphic species, it is not uncommon to encounter individuals that appear to exhibit both male and female secondary sex characteristics. Therefore, we tested the novel method of using a vibrator to sex turtles by stimulating male turtles to evert their penises. We tested this method on males of four species (three families) with known sexual dimorphisms: spiny softshell turtles ( Apalone spinifera ; n = 14), western chicken turtles ( Deirochelys reticularia miaria ; n = 17), Mississippi mud turtles ( Kinosternon subrubrum hippocrepis ; n = 10), and common musk turtles ( Sternotherus odoratus ; n = 9). The method accurately sexed 100% of A. spinifera, 64.7% of D. r. miaria , 80.0% of K. s. hippocrepis , and 55.6% of S. odoratus. Despite the low success rates in some species, there are situations in which this method will be useful for researchers working with species that are difficult to sex using external morphological characteristics.

Risque sénologique chez les patients transgenres : à propos des recommandations américaines sur le dépistage des néoplasies mammaires

Transgender patients have a poorly understood breast cancer risk despite their growing number and social acceptance. Epidemiological data are generally extrapolated from cisgender and postmenopausal women. A transgender woman is the result of the transition from male to female. These patients will benefit from hormone therapy based on estradiol in order to acquire female secondary sex characteristics. The incidence of breast neoplasia is similar to that of cisgender men. Nevertheless, it has later onset than for cisgender women and is often discovered at a more advanced stage. After the age of 50 years-old and after 5 years of hormone therapy, transgender women can benefit from a screening mammogram without a clearly defined rhythm. A transgender man is the result of the transition from female to male. These patients will benefit from hormone therapy based on testosterone in order to acquire male secondary sex characteristics. These patients can benefit from a total and bilateral mastectomy with nipple transplant called “top surgery”. Depending on family risk factors, the surgeon can prescribe a preoperative assessment, remaining at his discretion. Without breast surgery, only conventional biennial screening is admitted. Some guidelines recommend an annual clinical examination of the chest wall if “top surgery” has been done. Radiologists must know the specifics related to management of transgender patients for better care.

Zebrafish Nedd8 facilitates ovarian development and the maintenance of female secondary sexual characteristics via suppression of androgen receptor activity.

Nedd8 is a ubiquitin-like protein that covalently conjugates to target proteins through neddylation. In addition to cullin-RING ligases, neddylation also modifies non-cullin proteins to regulate protein activity, stability and localization. However, the roles of NEDD8 remain largely unknown in vivo Here, we found that loss of nedd8 in female zebrafish led to defects in oogenesis, disrupted oocyte maturation and stimulated growth of the breeding tubercles (BTs) on the pectoral fins. The BTs are normally present in males, not females. However, the loss of one copy of ar can partially rescue the phenotypes displayed by nedd8-null female zebrafish. Further assays indicated that Nedd8 conjugates to Ar and Ar is neddylated at lysine 475 and lysine 862. Moreover, Nedd8 conjugation efficiently suppressed Ar transcriptional activity. Lysine 862 (K862) of Ar is the key site modified by neddylation to modulate Ar transcriptional activity. Thus, our results not only demonstrated that Nedd8 modulates ovarian maturation and the maintenance of female secondary sexual characteristics of female zebrafish in vivo, but also indicated that androgen signaling is strictly regulated by nedd8.

A case of labioscrotal ovotestis in Madagascar with review of the literature

Among the disorder sexual development which regroups several pathological entities, true hermaphroditism or Ovotestis disorder remains a rare variety. We report a case of true hermaphroditism, diagnosed at the age of 15 years. Despite the presence of sexual ambiguity at birth, the female gender has been declared. The presence of a female genital tract and secondary sexual characteristics has led the choice of scrotal excision. The surgical procedure, the histological study bestow the positive diagnosis and allowed to revise the sexual ambiguity.

Sigmoid vaginoplasty in Mayer-Rokitansky-Kuster-Hauser syndrome

IntroductionMayer-Rokitansky-Kuster-Hauser syndrome (MRKH) is characterized by congenital aplasia of the uterus and upper 2/3 of the vagina, with normal female secondary sexual characteristics and a normal karyotype (46, XX). The frequency is 1/4500–5000 female births. The aim of this study was to report the management of MRKH syndrome with sigmoid vaginoplasty.Patients and methodThis study included 4 patients recruited over a 4-year period from February 2016 to January 2019. MRKH syndrome was retained in the presence of normal secondary sexual characteristics with normal external genitalia associated with vaginal aplasia and uterine agenesis. The approach was a laparotomy and a perineal approach under general anesthesia. The procedure involved the removal of a sigmoidal colonic graft that was anastomosed with the vaginal dimple.ResultsThe average age was 23 years. All patients had consulted for primary amenorrhea, infertility, and/or difficulties in sexual intercourse. The diagnosis of MRKH type 1 was retained in all patients. The average length of the vagina was 3.25 cm before surgery and 13.63 cm after surgery. The postoperative outcomes were uneventful in 3 patients. One patient developed anastomotic stenosis that was successfully treated with vaginal dilation for 2 weeks. The average postoperative follow-up was 30 months.ConclusionIn the context of a low-resource setting, sigmoid transposition represents a good procedure to treat vaginal aplasia and restore a satisfactory sexual activity to patients with MRKH type 1.

Ferredoxin 1b Deficiency Leads to Testis Disorganization, Impaired Spermatogenesis, and Feminization in Zebrafish.

The roles of steroids in zebrafish sex differentiation, gonadal development, and function of the adult gonad are poorly understood. Herein, we used ferredoxin 1b (fdx1b) mutant zebrafish to explore such processes. Fdx1b is an essential electron-providing cofactor to mitochondrial steroidogenic enzymes, which are crucial for glucocorticoid and androgen production in vertebrates. Fdx1b-/- zebrafish mutants develop into viable adults in which concentrations of androgens and cortisol are significantly reduced. Adult fdx1b-/- mutant zebrafish display predominantly female secondary sex characteristics but may possess either ovaries or testes, confirming that androgen signaling is dispensable for testicular differentiation in this species, as previously demonstrated in androgen receptor mutant zebrafish. Adult male fdx1b-/- mutant zebrafish exhibit reduced characteristic breeding behaviors and impaired sperm production, resulting in infertility in standard breeding scenarios. However, eggs collected from wild-type females can be fertilized by the sperm of fdx1b-/- mutant males by in vitro fertilization. The testes of fdx1b-/- mutant males are disorganized and lack defined seminiferous tubule structure. Expression of several promale and spermatogenic genes is decreased in the testes of fdx1b-/- mutant males, including promale transcription factor sox9a and spermatogenic genes igf3 and insl3. This study establishes an androgen- and cortisol-deficient fdx1b zebrafish mutant as a model for understanding the effects of steroid deficiency on sex development and reproductive function. This model will be particularly useful for further investigation of the roles of steroids in spermatogenesis, gonadal development, and regulation of reproductive behavior, thus enabling further elucidation of the physiological consequences of endocrine disruption in vertebrates.

Management of the patients with stage I germ cell ovarian tumors

The goal of the treatment of children and adolescents with germ cell ovarian tumors is to save both life and its quality. One of the quality of life issue in pediatric patients is fertility preservation. The removal of the ovary on the affected side allows saving the ovary on the opposite side. The single ovary is able to save further full development of female secondary sexual characteristics and will play important role as psychological value. In addition, the reproductive function will be stored. Chemotherapy may badly impact the function of a single ovary. To find out in advance how chemotherapy will affect ovarian function is impossible, so it is necessary for patients with Stage I ovarian germ cell tumors to decide the possibility of dismissing chemotherapy from the treatment. Under certain conditions unilateral salpingo-oophorectomy may be sufficient for stage I disease. Risk factors which should be considered when refusing chemotherapy are discussed.