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PubMed2003

Sex-specific apoptosis regulates sexual dimorphism in the Drosophila embryonic gonad.

Sexually dimorphic development of the gonad is essential for germ cell development and sexual reproduction. We have found that the Drosophila embryonic gonad is already sexually dimorphic at the time of initial gonad formation. Male-specific somatic gonadal precursors (msSGPs) contribute only to the testis and express a Drosophila homolog of Sox9 (Sox100B), a gene essential for testis formation in humans. The msSGPs are specified in both males and females, but are only recruited into the developing testis. In females, these cells are eliminated via programmed cell death dependent on the sex determination regulatory gene doublesex. Our work furthers the hypotheses that a conserved pathway controls gonad sexual dimorphism in diverse species and that sex-specific cell recruitment and programmed cell death are common mechanisms for creating sexual dimorphism.

Animals↗

PubMed2004

Bisphenol A induces feminization in Xenopus laevis tadpoles.

To evaluate possible estrogenic effects of bisphenol A (BPA) in an amphibian model, Xenopus laevis tadpoles were exposed to BPA and 17beta-estradiol (E2) during larval development. After metamorphosis, the gonadal phenotype was determined by gross morphology, and testes were further examined histologically to validate the results. BPA treatment altered the normal sex ratio toward females depending on the BPA concentrations added. Chemical analysis showed a time-dependent decline of BPA during semistatic exposure, indicating that BPA is taken up and metabolized to some extent by tadpoles. In addition, tadpoles were exposed to BPA and E2 for 2 weeks during sensitive stages of sexual differentiation. Afterward, the expression of an estrogenic biomarker, estrogen receptor (ER) mRNA, was assessed by semiquantitative RT-PCR. Both BPA and E2 up-regulated ER mRNA significantly. In conclusion, these results show clear evidence that BPA induces feminization in X. laevis tadpoles, revealing an estrogenic potency of BPA that influences sexual development in amphibians.

Animals↗

PubMed2006

A high-throughput gene knockout procedure for Neurospora reveals functions for multiple transcription factors.

The low rate of homologous recombination exhibited by wild-type strains of filamentous fungi has hindered development of high-throughput gene knockout procedures for this group of organisms. In this study, we describe a method for rapidly creating knockout mutants in which we make use of yeast recombinational cloning, Neurospora mutant strains deficient in nonhomologous end-joining DNA repair, custom-written software tools, and robotics. To illustrate our approach, we have created strains bearing deletions of 103 Neurospora genes encoding transcription factors. Characterization of strains during growth and both asexual and sexual development revealed phenotypes for 43% of the deletion mutants, with more than half of these strains possessing multiple defects. Overall, the methodology, which achieves high-throughput gene disruption at an efficiency >90% in this filamentous fungus, promises to be applicable to other eukaryotic organisms that have a low frequency of homologous recombination.

DNA Primers↗

PubMed1981

Plasma lipids in kidney transplanted children and adolescents: influence of pubertal development, dietary intake and steroid therapy.

Plasma triglycerides and/or cholesterol were significantly increased in twenty-four of thirty kidney transplanted children and adolescents with stable renal function, at least one year after the last rejection crisis who received low dose prednisone therapy. The cholesterol increment was related to both low density and high density lipoproteins. However, similar to findings in adult allograft recipients, these increases were very variable: six subjects had normal levels, eight had increased triglycerides, five increased triglycerides and cholesterol, and eleven increased cholesterol. No influence of renal function was found in this series of patients all of whom had plasma creatinine below 160 mumol/l. Subjects who had achieved sexual development had lower cholesterol values. An insignificant difference was observed between patients receiving daily and alternate-day steroid therapy, but a significant negative correlation was found between plasma triglycerides and fractional urinary excretion of 17 OH corticosteroids in the first 6 h after an oral dose of prednisone. Finally, no correlation was found between energy intake and triglycerides; but a significant correlation was observed between protein intake and plasma cholesterol. In conclusion, some patients show a high level of triglycerides and/or cholesterol after renal transplantation, possibly due to a different individual response to steroid therapy.

Adolescent↗

PubMed2004

Host intestinal epithelial response to Cryptosporidium parvum.

Cryptosporidium parvum is an obligate intracellular protozoan parasite that is a well-recognized cause of diarrhea in humans and animals throughout the world, and is associated with a substantial degree of morbidity and mortality in patients with the acquired immunodeficiency syndrome (AIDS). C. parvum primarily infects epithelial cells of the gastrointestinal tract, resulting in acute watery diarrhea for which there is no effective therapy. During infection, all parasite development, sexual or asexual, occurs within epithelial cells of the host. This requires a unique and complex association between two distinct eukaryotic organisms. Conversely, due to the intracellular nature of C. parvum, epithelial cells appear to play a key role in activating and communicating with the host immune system. Delineation of the biochemical processes that are regulated within infected epithelial cells is crucial for understanding the pathology of C. parvum infection, the process by which the host clears and ultimately develops resistance to infection, and the development of chemotherapeutic strategies to intercede infections.

Animals↗

PubMed2002

Regulation of sex-specific differentiation and mating behavior in C. elegans by a new member of the DM domain transcription factor family.

Mutations in Caenorhabditis elegans gene mab-23 cause abnormal male tail morphology and abolish male fecundity but have no obvious effect in the hermaphrodite. Here we show that mab-23 encodes a DM (Doublesex/MAB-3) domain transcription factor necessary for specific aspects of differentiation in sex-specific tissues of the male. mab-23 is required for the patterning of posterior sensory neurons in the male nervous system, sex muscle differentiation, and morphogenesis of the posterior hypodermis, spicules, and proctodeum. Failure of mab-23 mutant males to sire progeny is due primarily to defective sex muscle-mediated turning during copulatory behavior and likely compounded by impairment of sperm passage through the proctodeum. In the male nervous system, mab-23 refines ray neuron subtype distribution by restricting expression of dopaminergic neurotransmitter identity through interactions with the Hox gene egl-5 and a TGF-beta-related signaling pathway. mab-23 has distinct roles and functions independent of mab-3, indicating different aspects of C. elegans male sexual differentiation are coordinated among DM domain family members. Our results support the hypothesis that DM domain genes derive from an ancestral male sexual regulator and suggest how regulation of sexual development has evolved in distinct ways in different phyla.

Amino Acid Sequence↗

PubMed1982

[Precocious puberty in girls. Study of 98 cases].

A study of 98 cases of true sexual precocity in girls shows a frequency three times higher between 5 and 7 years than before age 5. Detectable causes (intracranial lesion and Mac Cune-Albright syndrome) were found in 56% of cases before 5 years and only 18% after age 5. The plasma levels of estradiol and gonadotropins and the gonadotropins response to LHRH did not differ significantly from those found at the corresponding stages of normal puberty. Plasma dehydroepiandrosterone was lower. Pelvic ultrasonography sometimes discovered follicular cysts. 44 patients treated with medroxyprogesterone acetate were followed for one or several years. Results on sexual development and plasma estradiol were good in most of them, with individual variations, Improvement in the ratio of bone age as height age and in the expected adult height was obtained but without statistical significance.

Child↗

PubMed1996

A longitudinal assessment of hormonal and physical alterations during normal puberty in boys. II. Estrogen levels as determined by an ultrasensitive bioassay.

A limited number of reports of estrogen levels in prepubertal and early pubertal boys have been published because previous estrogen assays have lacked adequate sensitivity to quantitate circulating estrogen concentrations. Development of a new ultrasensitive assay has permitted measurement of estrogen levels in 23 normally growing boys progressing through puberty. Concentrations were measured at approximately 4-month intervals over a 5- to 8-yr period. The levels increased with maturation in all and correlated directly with chronological age, bone age, weight, height, pubertal stage, and testosterone and insulin-like growth factor-I levels. Of these factors, the level of testosterone had the greatest influence on the estrogen concentration. The time from peak growth velocity also significantly correlated with estrogen level. The estrogen level correlated positively with growth velocity before the time of peak growth velocity and negatively after peak growth velocity. The estrogen levels first increased significantly an average of 3 yr after pubertal onset and reached a peak by 5 yr after pubertal onset. Peak growth velocity was attained an average of 3 yr after pubertal onset. The greatest increase in the rate of rise of the estrogen level was an 11-fold rise during the year in which puberty began. The next most significant increase was a 4.8-fold rise 3 yr after pubertal onset. With respect to pubertal stage, the greatest absolute change occurred from stage 4 to stage 5 and the greatest fold change occurred from stage 1 to stage 2. The estrogen level did not significantly correlate with the 24-h GH level. In conclusion, circulating estrogen levels are very low in all boys prepubertally and rise steadily during adolescent development. The estrogen level is closely related to testosterone concentration and to the time of peak growth velocity. These findings are consistent with the hypothesis that estrogen at low levels augments skeletal growth and maturation in boys (as well as girls). They are also consistent with the hypothesis that continued exposure to estrogen leads to epiphyseal fusion. Further studies are required to define the separate and combined roles of estrogen, GH, and testosterone, as well as other factors, on growth and sexual development at puberty.

Age Determination by Skeleton↗

PubMed1987

Sequences expressed sex-specifically in Drosophila melanogaster adults.

To obtain probes for sex-specific gene regulation during development in D. melanogaster, sequences expressed sex-specifically in adult flies were isolated by differential cDNA hybridization screens of a genomic library. Ten clones define new sex-specifically expressed genes. The remaining three isolates correspond to previously cloned genes encoding female-specific yolk proteins and chorion proteins. The pattern of expression of these genes in sex determination mutants and in germlineless flies, as well as their tissue specificities, permitted us to distinguish transcripts whose expression is dependent on correct sexual development of the soma or the germline. One of the female transcripts is expressed in nurse cells and oocytes. Five of the male-specific sequences are expressed in the testis during spermatogenesis: the remaining one is expressed in the soma. Experiments using a temperature-sensitive allele of tra-2 show that the presence of this male-specific transcript, found only in the adult paragonia, is not affected by temperature shift of X/X; tra-2ts2 adults. This is in contrast to yolk protein genes, which require tra-2 function in the adult for their expression in the female fat body.

Animals↗

PubMed2001

Neuroendocrine features of pubertal development in females with mental retardation.

In order to evaluate the hypothalamic-pituitary effects of mental retardation during pubertal development, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) responses to gonadotropin-releasing hormone (GnRH) administration were evaluated at various pubertal stages in a female population with mental retardation (MR) compared to a healthy control group of adolescents. Fifty-six girls aged 8-16 years with MR and 146 normal females of the same age participated in the study. The analyzed subjects were divided into different pubertal stages, ranging from P2 to P5, in line with their degree of sexual maturation. Each patient underwent a GnRH test (100 micrograms); blood samples were collected basally and 15, 30, 60, 90 minutes after the GnRH injection. FSH and LH were assayed in each sample; the gonadotropin response to GnRH administration was evaluated as incremental area. No differences were found at any pubertal stage between the two studied groups with regard to the age, body mass index, or age at menarche. Patients with mental retardation during stages P2 and P3 showed lower FSH secretion in response to GnRH bolus compared with control subjects (P2, p < 0.05; P3, p < 0.01). In conclusion, our data show that MR is related to an impaired response of the FSH-secreting pituitary cells to their appropriate stimulus; this feature is present only in the initial pubertal stages, whereas it disappears during sexual development.

Adolescent↗

PubMed2004

Peptide pheromones in newts.

This article reviews the current state of understanding of reproductive pheromones in amphibians, focusing mainly on the purification and characterization of peptide pheromones in newts of the genus Cynops, molecular cloning of cDNAs encoding the pheromone molecules, and hormonal control of secretion of these pheromones. Pheromones that attract sexually developed female Cynops pyrrhogaster and C. ensicauda newts were isolated from the male abdominal glands. The C. pyrrhogaster and C. ensicauda pheromones are peptides, designated sodefrin and silefrin, with the amino acid sequences SIPSKDALLK and SILSKDAQLK, respectively. Each pheromone attracts only conspecific females. Molecular cloning of cDNAs encoding sodefrin and silefrin revealed the presence of precursor proteins that are considered to generate these pheromone peptides. Pheromone precursor mRNA levels and radioimmunoassayable pheromone concentrations in the abdominal glands were elevated by prolactin and androgen. Sexual dimorphism and hormone dependency of the responsiveness of vomeronasal epithelium to sodefrin were noted. Significance of pheromones in the form of peptide for those performing reproductive behavior in an aquatic environment was also discussed.

Animals↗

PubMed2005

Evaluation of the auxological and metabolic status in prepubertal children born small for gestational age.

BACKGROUND: Low birth weight (BW) (<2,500 g) is associated with a high risk of impaired postnatal growth and late metabolic consequences. The aim of this study is to describe the postnatal growth pattern and the metabolic status of children born small for gestational age (SGA) and compare them with premature children born with low (1,500-2,500 g) and very low (<1,500 g) BW. CHILDREN AND METHODS: 104 prepubertal children (47 males and 57 females) aged 3.0 to 8.9 years were divided into four groups according to their birth weight adjusted for gestational age (GA): SGA-premature (SGApr): BW < -2 SD, GA <37 wk (n = 17); SGA-full-term (SGAt): BW < -2 SD, GA >37 wk (n = 29); low birth weight (LBW): BW = 1,500-2,500 g, GA <37 wk (n = 35); very low birth weight (VLBW): BW <1,500 g, GA <37 wk (n = 23). The control group consisted of 27 full-term appropriate for gestational age, prepubertal children matched for age. All children had anthropometric and laboratory measurements. The HOMA model was used to estimate insulin resistance (IR). RESULTS: Weight, height and body mass index (BMI) were significantly lower in the SGA groups -- both term and premature -- (p <0.05) and particularly lower in the VLBW children (p <0.01). At the age of 36 months, 99.6% of SGAt and a smaller percentage of SGApr (88.2%) children achieved catch-up growth. IGF-I and IGFBP-3 levels were lower in the children born SGA, both term and premature, compared to the controls (p <0.05) and especially in those who had catch-up after the age of 6 months (p <0.002). VLBW children aged 6-8.9 years had significantly higher HOMA compared to controls of the same age group (p = 0.005), whereas no evidence of IR was found in the SGA children. None of the children had developed premature adrenarche by the day of examination. CONCLUSIONS: Prepubertal children born SGA and VLBW are thinner and shorter than their age-matched controls. A larger percentage of SGA full-term children achieve catch-up growth than SGA premature children by 3 years of age. SGA children and especially those with late catch-up growth have lower IGF-I levels. Children with VLBW show evidence of IR at age 6-8.9 years. None of the girls showed precocious sexual development by the day of examination.

Body Height↗

PubMedDate not supplied

Skewed X-chromosome inactivation pattern in SRY positive XX maleness: a case report and review of literature.

XX maleness is the most common condition in which testes develop in the absence of a cytogenetically detectable Y chromosome. Using fluorescence in situ hybridization (FISH) or PCR, it was possible to detect the transfer of Yp fragments including SRY gene to the terminal part of X chromosome in the majority of XX males. We report a 32-year-old-male in whom a seminal analysis showed azoospermia, an X chromatin analysis showed 44% of Barr body positive nuclei and a chromosomal analysis revealed a 46,XX karyotype. Physical examination showed a normal sexual development and bilateral small testes. Hormonal studies revealed hypergonadotropic hypogonadism. Testis histological examination showed a profile of Sertoli Only Cell Syndrome. FISH study ruled out the presence of a Y-bearing cell line, and confirmed translocation of SRY to Xp terminal part. In order to confirm that the complete masculinized phenotype was related to a preferential inactivation of the no rearranged X chromosome, X-chromosome inactivation patterns (XCIP) were studied by analysis of methylation status of the androgen receptor gene. Highly skewed XCIP was observed by greater than 90% preferential inactivation involving one of the two X chromosomes, suggesting that the SRY-bearing X chromosome was the preferentially active X allowing for sufficient SRY expression for complete masculinization.

Adult↗

PubMed1989

[Endocrinological development in girls during puberty].

I) Endocrinological changes in girls during puberty are characterized by the progressive elevation of pituitary, ovarian and adrenal hormones except PRL. Longitudinal study revealed significant increases in both LH, FSH and estradiol occurred between 2 years to one year before menarche. PRL levels, however, increased between 3 to 2 years before menarche and the levels dropped significantly one year before the onset of the first menses. Serum levels of androstenedione and estrone in girls were higher than that in boys. Among steroids, the levels of 5 alpha-androstanediol decreased significantly before the menarche suggesting the physiological role of this hormone on the onset of puberty. In regard to the correlation between hormone levels and sexual developments, DHA-S levels and body weights correlated well with the breast development. Grasping power correlated well with serum testosterone levels in girls. II) The clinical and endocrinological aspect of menstrual disorders during adolescent were also examined. The majority of the patients complaining of functional uterine bleeding and amenorrhea showed high LH and normal FSH levels. Episodic secretion of LH was absent in girls of primary and secondary amenorrhea due to hypothalamic impairment.

Adolescent↗

PubMed1976

Effects of childhood leukemia and chemotherapy on puberty and reproductive function in girls.

Longer survivial in childhood leukemia prompted this study of pubertal development and reproductive function in 35 girls and women. Twenty-eight patients (80 per cent) had normal pubertal progression during a median of 74 months after diagnosis of leukemia and 49 months of chemotherapy. Seven patients were abnormal: four exhibited hypothalamic-pituitary dysfunction with suppression of circulating serum gonadotropins (less than 6 mlU per milliliter); three others had evidence of primary ovarian dysfunction - reversible in two - with inappropriately elevated circulating serum gonadotropins (follicle-stimulating hormone greater than 20 mlU per milliliter). Normal sexual development correlated best with pubertal status at onset of leukemia; only one of 17 patients with diagnosis before puberty experienced altered pubertal progression, whereas abnormalities appeared in six of 18 with onset during puberty or after menarche. Thus, most girls with aggressively treated child-hood leukemia have an excellent prognosis for normal hypothalamic-pituitary-ovarian function; normal development is further enhanced in patients who are prepubertal at onset of leukemia.

Adolescent↗

PubMedDate not supplied

Use of a rat cDNA probe specific for the Y chromosome to detect male-derived cells.

A cDNA probe that exhibits specificity for the rat Y chromosome was generated by using a set of primers specific to the murine Sry gene, the sex-determining region of the Y chromosome. A 459-base pair (bp) DNA fragment was obtained by polymerase chain reaction (PCR) amplification from male, but not female, rat genomic DNA (EMBL Nucleotide Sequence Database accession number X89730). This DNA fragment was purified, cloned using a vector, and digested with EcoR1 to yield a 270-bp DNA fragment. This 270-bp cDNA fragment, when used as a probe in Southern blot analysis of rat DNA, was observed to bind to three separate bands of approximately 2.3, 5.0, and 7.0 kb in size. The binding was demonstrated with male, but not female, genomic DNA. Another set of primers was generated to sequences within the 270-bp fragment that produced a PCR product of 104 bp. This DNA fragment, when used as a probe in Southern blot analysis, enabled PCR detection of at least 0.1% male cells in a mixed population of female cells. These cDNA probes should prove useful in studies designed to track cell populations (e.g., tumor metastasis and hemopoietic cells after bone marrow transplantation) in syngeneic male/female pairs. In addition, a cDNA probe that is specific for the rat Sry gene might be valuable in studies of fetal male sexual development or the study of spermiogenesis.

Animals↗

PubMed2006

The adolescent decline of NREM delta, an indicator of brain maturation, is linked to age and sex but not to pubertal stage.

Two dramatic phenomena of human adolescence are sexual maturation and a steep decline in the delta EEG of non-rapid eye movement (NREM) sleep. It has long been speculated that these developmental changes are causally related. Here, we present the first longitudinal data on this issue. Cohorts of 9- and 12-year-old children (n = 31, 38) were studied with in-home sleep EEG recordings at 6-mo intervals over 2 years. Pubertal (Tanner) stage, height, and weight were obtained at each time point. NREM delta power density (DPD) did not change significantly over ages 9-11 years, and its level did not differ in boys and girls. DPD declined by 25% between ages 12 and 14 years. This decline was parallel in the two sexes, but levels were lower in girls, suggesting that their DPD decline began earlier. Mixed effect analyses demonstrated that DPD was strongly related to age with Tanner stage, height, weight and body mass index controlled but that none of these measures of physical and sexual development was related to DPD with age controlled. NREM delta is the sleep EEG component homeostatically related to prior waking duration and the intensity of waking brain activity. We hypothesize that the DPD decline is caused by age-programmed synaptic pruning that decreases waking brain metabolic rate. This reduced rate would decrease the "substrate" for delta homeostasis. Whether or not this interpretation proves correct, these longitudinal data demonstrate that the delta decline in adolescence reflects brain processes that are not predicted by physical growth or sexual maturation.

Adolescent↗

PubMed1974

Arginine vasotocin: effects on development of reproductive organs.

Immature 25-day-old mice were injected daily with 1 microgram of arginine vasotocin for 3 or 4 days and killed 24 hours after the last injection. The ovaries were 30 percent smaller in treated females than in controls. The ventral prostates and accessory organs (seminal vesicles and coagulating glands) were less than half the size of these structures in control males. Similar results were observed when 15-day-old mice were given similar injections and killed 2 weeks after the last injection; furthermore, testis weights were 28 percent smaller than those of controls. It is speculated that arginine vasotocin, which has been found in mammalian pineal glands, might mediate effects of the pineal gland on normal sexual development.

Age Factors↗