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Jorma Toppari

Publications and source records attributed to Jorma Toppari.

63 records · Page 4Linked to original sources
PubMed2002

Natal and neonatal teeth in relation to environmental toxicants.

Infants born to mothers heavily exposed to polychlorinated biphenyls (PCBs) and dibenzofurans (PCDFs) have earlier been reported to have increased prevalences of natal and neonatal teeth. Some tendency toward higher prevalence figures of natal and neonatal teeth can be seen in the literature in normal child populations during the last 40 y. We therefore decided to determine the present prevalence of these teeth in a Finnish population and to evaluate whether infants with natal and neonatal teeth are more exposed to PCBs, PCDFs, and polychlorinated dibenzo-p-dioxins (PCDDs) than infants on average. A total of 34,457 infants born in 1997-2000 in four hospitals in southern Finland were examined for natal and neonatal teeth. The exposure of the infant to PCBs and PCDD/Fs was evaluated by measuring the levels of 17 most toxic PCDD/F and 36 PCB congeners in his or her mother's milk sample when the child was 4-8 wk old. A total of 34 infants had one or two natal (29 infants) or neonatal teeth (five infants). The milk analyses showed that the median level of PCDD/Fs as toxic equivalent (World Health Organization-recommended 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalent quantity for PCDD/Fs in fat) was 11.9 pg/g in fat, and that of PCBs (World Health Organization-recommended 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalent quantity for PCBs) was 7.24 pg/g in fat. These levels corresponded to the prevailing levels. The results showed that the prevalence of natal and neonatal teeth was 1:1000. No association was found between pollutant levels and occurrence of natal and neonatal teeth, indicating that the prevailing levels of PCDD/Fs and PCBs are likely to be below the threshold to cause perinatal eruption of teeth.

Adult↗
PubMed2002

Gender difference in breast tissue size in infancy: correlation with serum estradiol.

Breast tissue in newborn infants is considered to be physiologic and mainly related to exposure to maternal hormones in utero or through breast-feeding. However, controversy exists as to whether breast tissue in later infancy is under the influence of endogenous hormones. Children at 2-4 mo of age have a surge of reproductive hormones, including estradiol, which may affect the mammary gland. In a prospective cohort study of 1126 healthy, 3-mo-old infants, breast tissue size and reproductive hormones were measured. We found that palpable breast tissue (diameter >or=3 mm) is a common physiologic condition present in 78.9% of children, significantly more frequent (p < 0.001) and larger (p < 0.001) in girls than in boys. Girls had significantly higher median estradiol levels than boys (30.0 versus 21.0 pmol/L, p < 0.001). In a multiple regression model including breast tissue size given as quartiles as the dependent variable and weight for gestational age, subscapular skinfold, weight at 3 mo of age and serum estradiol as independent variables, a gender difference was shown. In girls, the estradiol level was positively (p < 0.03) correlated to breast quartile. In boys, no correlations were found. Whether the stimulation of the mammary gland in infancy represents a developmental window that is of biologic significance for breast development and pathology in adulthood remains to be defined.

Anthropometry↗
PubMed2002

Early postnatal treatment of hypogonadotropic hypogonadism with recombinant human FSH and LH.

BACKGROUND: Patients with hypogonadotropic hypogonadism may be diagnosed shortly after birth because of micropenis and cryptorchidism, combined with subnormal LH and FSH concentrations during the postnatal period. OBJECTIVE: To investigate whether treating these patients with gonadotropins postnatally, to mimic the physiological development, would improve testicular growth and fertility potential later in life. DESIGN: Our patient presented with micropenis. Serum hormone concentrations were measured monthly after delivery: LH and testosterone were undetectable, and FSH and inhibin B were below the normal range (0.05-0.17 IU/l and 79-112 pg/ml respectively). METHODS: From 7.9 to 13.7 months of age, the patient was treated with recombinant human LH and FSH in doses of 20 and 21.3 IU s.c. twice weekly respectively. RESULTS: During treatment concentrations of LH, FSH, inhibin B and estradiol increased to values within normal limits (0.7-1.88 IU/l, 0.17-3.24 IU/l, 121-268 pg/ml and 40-55 pmol/l respectively), whereas serum testosterone remained undetectable. Penile length increased from 1.6 to 2.4 cm and testicular volume, assessed by ultrasound, increased by 170%. No significant adverse events were observed. CONCLUSIONS: Gonadotropin treatment in an infant with hypogonadotropic hypogonadism succeeded in inducing an increase in inhibin B and testicular growth.

Follicle Stimulating Hormone↗
PubMed2002

Developmental expression and spermatogenic stage specificity of transcription factors GATA-1 and GATA-4 and their cofactors FOG-1 and FOG-2 in the mouse testis.

OBJECTIVE: The transcription factors GATA-1 and GATA-4 have been implicated in the regulation of testicular development and function. Their cofactors FOG-1 and FOG-2 are expressed in the gonads, but their cell-specific and developmental expression in the testis remains unresolved. Therefore, we analyzed GATA-1, GATA-4, FOG-1 and FOG-2 expression in detail, from undifferentiated male urogenital ridge to adult testis. METHODS: Immunohistochemistry and in situ hybridization were applied on mouse testicular samples. RESULTS: GATA-4 and FOG-2, but not GATA-1 or FOG-1, were expressed as early as in the male urogenital ridge. FOG-2 expression was localized in the Sertoli cells at embryonal day 12.5 (E12.5), but it diminished with advancing fetal testicular development. In E17.5 testis, FOG-2 was present only in the testicular capsule and a subset of fetal Leydig cells. FOG-1 was expressed from E15.5 Sertoli cells onwards, whereas GATA-1 was not detected during the fetal period at all. In the postnatal testis, FOG-2 was abundantly expressed immediately after birth, but in adult testis its expression was predominantly restricted to stage VII-XII seminiferous tubules. Stage specificity was also found for FOG-1, which, similarly to GATA-1, was abundantly expressed in stage VII-XII tubules during adulthood. CONCLUSIONS: Our results indicate that FOG-2, in addition to GATA-4, has a role in early gonadal development and sexual differentiation, and FOG-1 at later fetal stages, while GATA-1 executes its action postnatally. The findings suggest that, in contrast to the hematopoietic system and the heart, GATA-1 and GATA-4 do not use FOG-1 and FOG-2 respectively as their only cofactors during the early stages of testicular development.

Aging↗
PubMedDate not supplied

Evidence for a role of glycogen synthase kinase-3 beta in rodent spermatogenesis.

Glycogen synthase kinase-3 beta (GSK-3 beta) regulates cell metabolism, cell cycle, and cell fate through the phosphorylation of a diverse array of substrates. Herein, we provide evidence that supports a role for GSK-3 in mammalian meiosis and spermatogenesis. Immunostaining of testis sections showed that while GSK-3 alpha was ubiquitous in the seminiferous tubules, GSK-3 beta was expressed in premeiotic type B spermatogonia, in both meiotic preleptotene and leptotene spermatocytes, as well as in Sertoli cells in both the mouse and rat. Thus, GSK-3 beta is expressed in germ cells entering meiosis. In addition, intense immunoreactivity was detected in rat step 6 though 11 spermatids. In situ hybridization (ISH) in rat testis confirmed the immunostaining pattern in leptotene and spermatids and showed a GSK-3 beta messenger RNA (mRNA) signal in some pachytene spermatocytes. The restricted pattern of expression suggests cell-specific regulation of Gsk-3 beta mRNA. To determine whether GSK-3 is required for meiosis entry, rat stage VIIa seminiferous tubule segments were cultured with selective small-molecule GSK-3 inhibitors. These compounds markedly and dose-dependently suppressed meiotic synthesis (S)-phase DNA. Since a yeast GSK-3 homolog, Rim11p (regulator of inducer of meiosis), is pivotal to meiosis entry, we tested whether GSK-3 beta complements Rim11p function in meiosis. Rim11p phosphorylates transcription factors Ume6p (unscheduled meiotic gene expression) and Ime1p (inducer of meiosis) to induce meiosis entry. Overexpression of murine GSK-3 beta in a rim11 mutant yeast failed to rescue the sporulation defect. Our finding that GSK-3 beta interacted only with Ume6p but not with IME1 in a yeast 2-hybrid assay suggests that noncomplementation reflects partial divergence in substrate specificity. This work provides the basis for future studies of GSK-3 beta signaling in mammalian meiosis and spermatogenesis.

Amino Acid Sequence↗
PubMedDate not supplied

Effects of 4-tert-octylphenol, 4-tert-butylphenol, and diethylstilbestrol on prenatal testosterone surge in the rat.

In the present study, we evaluated the effects that 4-tert-octylphenol (OP) and 4-tert-butylphenol (BP) had on the prenatal testicular testosterone surge at embryonic day (ED) 19.5 in the rat. In utero exposure to alkylphenols (0.1-100 mg/kg maternal weight) on EDs 13.5, 15.5, and 17.5 did not decrease testicular testosterone content, whereas exposure to diethylstilbestrol (DES) caused a significant depression in testosterone synthesis and secretion. The depression was maintained during ex vivo tissue culture. In order to elucidate the observed differences in the in vivo effects between alkylphenols and DES, the exposures were also carried out in tissue culture of intact ED 19.5 testes. Basal testosterone, progesterone, cAMP production and hCG-induced testosterone levels were determined during and after a 3-h culture period. DES (100 mg/l) did not alter testosterone production but caused a two-fold increase in progesterone. OP (10, 100, 500 mg/l) and BP (100 mg/l) significantly increased testosterone and progesterone levels by up to seven-fold. In the presence of BP 100 mg/l, however, the intratesticular testosterone content did not correlate with the significantly increased fraction of secreted, or leaked, testosterone. The latter was correlated with tissue damage observed at electron microscopic level. Consistent with this, BP 500 mg/l elevated testicular testosterone level slightly during the first hour in the culture but the level subsequently returned to the control value. At the electron microscopic level, alkylphenols caused most severe changes in Leydig cell membrane structures and lipid droplets. In the DES-treated testes, membrane vesicle formation around the lipid droplets and increased mitochondrial pleiomorphy were observed. Altogether, the present in vivo and in vitro analyses confirm different effects of alkylphenols and DES on fetal rat steroidogenesis and tissue structure.

Animals↗
PubMedDate not supplied

Lack of LGR8 gene mutation in Finnish patients with a family history of cryptorchidism.

Cryptorchidism is the most frequent congenital anomaly of the urogenital tract in the male. Although in Western countries 1-2% of males at the age of 3 months are diagnosed with this condition, its aetiology is still unknown. Animal models suggest a possible genetic basis for this disorder. Recently, the INSL3 (Leydig insulin-like peptide) gene and its cognate receptor, LGR8, were found to be important in testicular descent by regulating gubernacular development. Male mice null for either INSL3 or LGR8 genes exhibited bilateral cryptorchidism. Because earlier studies indicated that mutation of the INSL3 gene is not associated with the development of human cryptorchidism, this study analysed whether mutations in the LGR8 gene could be associated with this disorder. Sequencing of 18 exons of the LGR8 gene in 23 cryptorchid Finnish patients and a group of 33 control subjects allowed the identification of three nucleotide changes in exons 12 and 17, showing single base substitutions from A to G at positions 957, 993, and 1810 of LGR8. Among the three changes, only the 1810 A to G substitution is associated with an amino acid change from isoleucine to valine (Ile604Val) located in the fifth transmembrane domain of this seven-transmembrane receptor. This change was more frequent in a control group of normal fertile adult males and infant boys than in the group of cryptorchid males. The change is not associated with altered receptor signalling, thus suggesting the presence of a polymorphism unrelated to the cryptorchid phenotype. These data indicate that mutations involving the human LGR8 gene do not represent a frequent cause of cryptorchidism in the Finnish population.

Adult↗
PubMedDate not supplied

Genetics and hormones in testicular descent.

Testicular descent is an essential part of normal male sexual development. Any anomaly that disrupts normal testicular descent will be clinically evident as cryptorchidism. Several factors, such as Hoxa-10, epidermal growth factor (EGF), calcitonin gene-related peptide (CGRP), and hormones, especially androgens and insulin-like factor 3 (INSL-3), have been suggested as being regulators of testicular descent. Testicular descent from the lower pole of the kidney into the extra-abdominal scrotal sac is a two-stage process of transabdominal and inguino-scrotal migration. The transabdominal phase is androgen independent, whereas the inguino-scrotal phase depends on androgen action. Disruption of androgen action eg. by environmental anti-androgens are suspected as contributing to cryptorchidism. Estrogens can down-regulate INSL-3 production and thereby disturb testicular descent. Familial occurrence in some cases suggests a possible genetic background for cryptorchidism.

Journal Article↗