• Development and Reproduction
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• v.20 no.2
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• pp.91-99
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• 2016

Lipopolysaccharide (LPS), an endotoxin, elicits strong immune responses in mammals. Several lines of evidence demonstrate that LPS challenge profoundly affects female reproductive function. For example, LPS exposure affects steroidogenesis and folliculogenesis, resulting in delayed puberty onset. The present study was conducted to clarify the mechanism underlying the adverse effect of LPS on the delayed puberty in female rats. LPS was daily injected for 5 days ($50{\mu}g/kg$, PND 25-29) to treated animals and the date at VO was evaluated through daily visual examination. At PND 39, animals were sacrificed, and the tissues were immediately removed and weighed. Among the reproductive organs, the weights of the ovaries and oviduct from LPS-treated animals were significantly lower than those of control animals. There were no changes in the weights of uterus and vagina between the LPS-treated and their control animals. immunological challenge by LPS delayed VO. Multiple corpora lutea were found in the control ovaries, indicating ovulations were occurred. However, none of corpus luteum was present in the LPS-treated ovary. The transcription level of steroidogenic acute regulatory protein (StAR), CYP11A1, CYP17A1 and CYP19 were significantly increased by LPS treatment. On the other hand, the levels of $3{\beta}$-HSD, $17{\beta}$-HSD and LH receptor were not changed by LPS challenge. In conclusion, the present study demonstrated that the repeated LPS exposure during the prepubertal period could induce multiple alterations in the steroidogenic machinery in ovary, and in turn, delayed puberty onset. The prepubertal LPS challenge model used in our study is useful to understand the reciprocal regulation of immune (stress) - reproductive function in early life.

• Journal of Environmental Health Sciences
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• v.47 no.3
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• pp.245-258
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• 2021

Objectives: In many previous studies, endocrine disruptors (EDCs) have been found to affect delays in puberty. Various EDCs have been reported on, but there have been only limited epidemiologic studies on the effects of exposure to environmental heavy metals and pyrethroid pesticides on puberty delay. Therefore, the aim of this study was to investigate the association of exposure to environmental mercury, cadmium, and pyrethroid pesticides with delayed puberty in children based on national survey data that represents Korean children. Methods: We selected 450 children at the ages of 9-11 years old from the third Korean National Environmental Health Survey (3rd KoNEHS). The relations of urinary Hg, Cd, and 3-PBA with pubertal development were evaluated using multiple logistic regression analyses. Results: Urinary Hg levels were significantly associated with delayed puberty in boys [testicle development: OR=0.41 (95% CI: 0.20, 0.84); genitalia development: OR=0.35 (95% CI: 0.15, 0.81)]. Girls with higher Hg levels were more likely to experience delayed menarche [OR=0.23 (95% CI: 0.06, 0.90)]. We observed a significant 49% reduction in odds for menarche per increasing unit of urinary cadmium levels [OR=0.51 (95% CI: 0.24, 1.01)]. In addition, urinary 3-PBA showed a negative association with genitalia development in boys and menarche in girls [genitalia development: OR=0.73 (95% CI: 0.55, 0.96); menarche: OR=0.56 (95% CI: 0.32, 1.00)]. Conclusions: The results of this study support the hypothesis that exposure to environmental mercury, cadmium and pyrethroid pesticides may affect puberty delays. Additional evidence needs to be obtained through further prospective studies.

• Clinical and Experimental Pediatrics
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• v.53 no.5
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• pp.661-665
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• 2010

Anemia caused by vitamin B12 deficiency resulting from inadequate dietary intake is rare in children in the modern era because of improvements in nutritional status. However, such anemia can be caused by decreased ingestion or impaired absorption and/or utilization of vitamin B12. We report the case of an 18-year-old man with short stature, prepubertal sexual maturation, exertional dyspnea, and severe anemia with a hemoglobin level of 3.3 g/dL. He had a history of small bowel resection from 50 cm below the Treitz ligament to 5 cm above the ileocecal valve necessitated by midgut volvulus in the neonatal period. Laboratory tests showed deficiencies of both vitamin B12 and iron. A bone marrow examination revealed dyserythropoiesis and low levels of hemosiderin particles, and a cytogenetic study disclosed a normal karyotype. After treatment with parenteral vitamin B12 and elemental iron, both anemia and growth showed gradual improvement. This is a rare case that presented with short stature and delayed puberty caused by nutritional deficiency anemia in Korea.

• Animal cells and systems
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• v.4 no.4
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• pp.367-373
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• 2000

In the present study we determined if NELL2, a neural tissue-specific protein containing 6 epidermal growth factor (EGF)-like repeat domains, plays an important role in the regulation of puberty initiation in the rat hypothalamus. We origin811y found that NELL2 is a new estrogen-responsive gene in hypothalami derived from estrogen-sterilized and control rats using a PCR differential display. In the 40-day-old female rat hypothalamus, NELL2 was up-regulated by neonatal estrogen treatment. In situ hybridization histochemistry showed that NELL2 is very abundant in the ventromedial hypothalamic nucleus that is responsible for the control of sex behavior. NELL2 mRNA level in the medial basal hypothalamus showed a dramatic increase before female puberty onset, which suggests that NELL2 may be involved in the process regulating female puberty onset. We attemped to block NELL2 synthesis with intracerebroventricular injection of an antisense oligodeoxynucleotide (ODN) to the NELL2 mRNA, and examined its effect on the puberty onset of the female rat. The antisense ODN significantly delayed puberty initiation determined by vaginal opening. In summary, NELL2 may play an important role in the regulation of female puberty onset.

• Animal cells and systems
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• v.3 no.3
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• pp.319-329
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• 1999

Onset of female puberty follows a series of prepubertal cellular and molecular events including changes of synaptic plasticity, synthetic and releasing activity and gene expression. Dramatic increase of gonadal steroid level is one of the most prominent changes before the onset of puberty. Based on the importance of steroid feedback upon the hypothalamus, we adopted an estrogen sterilized rat (ESR) model where 100 ng of 17$\eta$-estradiol were administered into neonatal pubs for 7 days after birth. To identify genes involved in the onset of female puberty, we applied PCR differential display using RNA samples derived from ESR and control rat hypothalami. About 100 out of more than 1000 RNA species examined displayed differential expression patterns between a 60-day old control rat and ESR. Sequence analysis of differentially amplified PCR products showed homology with genes such as mouse kinesin superfamily-associated protein 3 (KAP3) and several cDNAs previously described by others in mouse and human tissues. Several gene products such as 2-1 and 8-1 corresponded to novel DNA sequences. We analyzed mRNA levels of KAP3, 2-1 and 8-1 genes in the hypothalami derived from neonatal, 6-, 28-, 31-, and 40-day old rats. Northern blot analysis showed that mRNAs of KAP3, 2-1 and 8-1 genes were markedly increased before the initiation of puberty. Neonatal treatment of estrogen clearly inhibited prepubertal increases in KAP3, 2-1 and 8-1 mRNA levels. Therefore, these genes may play important roles in the initiation of hypothalamic puberty. In addition, intracerebroventricular (icv) injection of antisense KAP3 oligodeoxynucleotide (ODN) clearly delayed puberty initiation determined by vaginal opening, which further confirmed that KAP3 plays an important role in the regulation of puberty initiation.

• Molecules and Cells
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• v.22 no.1
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• pp.30-35
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• 2006

Munc18, a mammalian homolog of C. elegans Unc, is essential for neurotransmitter release. The aim of this study was to identify estrogen-dependent expression of Munc18-1 and its role in the regulation of glutamate release for puberty onset. Hypothalamic munc18-1 mRNA levels were significantly increased by estrogen treatment in ovariectomized, immature female rats. During pubertal development, the munc18-1 mRNA levels dramatically increased between the juvenile period and the anestrous phase of puberty. Intracerebroventricular administration of an antisense oligodeoxynucleotide against munc18-1 mRNA significantly decreased glutamate release and delayed the day of puberty onset. These results suggest that Munc18-1, expressed in an estrogen-dependent manner, plays an important role in the onset of female puberty via the regulation of glutamate release.

• Korean Journal of Community Nutrition
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• v.5 no.1
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• pp.50-62
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• 2000

This study was conducted with 20 female gymnasts to examine the relationship between eating patterns, diet menstrual function and hematological status. According to the baseline data a nutrition counseling and education program was developed and evaluated improved the nutritional status and health of female gymnasts. Mean body weight at the onset of the study was 42.1$\pm$7.0kg and was reduced to 41.8$\pm$6.1kg after the nutrition counseling and education program. The percent of body fat was significantly reduced from 13.9$\pm$3.7% to 13.1$\pm$3.1%(p<0.01) skinfold thickness of subscapular and thighs was reduced significantly(p<0.01, p<0.05) Mean daily intake levels of energy, protein calcium iron thiamin riboflavin and niacin were significantly elevated after the nutrition counseling and education program but were lower than the Recommenced Dietary Allowances. For the nutrition knowledge and food habits, the posttest mean scores showed a significant increase. The hematological status(hematocrit, serum ferritin) and the early follicle level of estradiol were elevated to a mild degree although it was not significant,. The follicular stimulating hormone level was elevated significantly(p<0.01) Gymnastica has been one of the sports implicated by the medical profession as having probable detrimental effects. The implications of such training to childs growth and maturation have yet to be determined . Most female athletes, however, experience poor nutritional status and delayed puberty The priorities were to prepared a more effective nutrition program and education material status and delayed puberty. The priorities were prepared a more effective nutrition program and educational material for athletes coaches and adminstrators to prepare guidelines for the team physicians and coaches to follow for the physical and physiological examinations of female athletes.

• Journal of Animal Reproduction and Biotechnology
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• v.36 no.1
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• pp.25-34
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• 2021

Kisspeptin is a key player in the central control of reproductive axis. Central administration of kisspeptin has been shown to advance puberty in rats. Stimulation of hypothalamic GnRH pulse generating mechanism by kisspeptin has been proposed to be the mechanism behind the onset of puberty. We hypothesized that chronic high doses of kisspeptin administration suppresses the reproductive axis and hence delays the pubertal onset. Hence, we investigated the effect of peripheral administration of chronic high doses of kisspeptin on pubertal onset, feed intake and body weight in female rats. Rats were treated with saline or kisspeptin (100 nmoles per day; intraperitoneal) for 26 days (day 25 to day 50 postnatal) and the day of vaginal opening was marked as day of puberty. Kisspeptin treated rats had delayed pubertal onset and reduced feed intake and body weight. Gonadal GPR54 mRNA was reduced suggesting that chronic high doses of kisspeptin may suppress the reproductive functions possibly by downregulation of GPR54 receptor. However, delay in puberty due to reduction in feed intake and body weight could not be ruled out in this study. Further, our study emphasizes the importance of dosage and duration of kisspeptin administration in the manipulation of reproductive axis. Our study, for the first time, suggests that kisspeptin and its analogues, if proven beneficial, could be used to treat precocious puberty in children. It appears that, though a promising tool for enhancing fertility, kisspeptin acts as a double-edged sword and has to be cautiously used to manipulate reproduction.

• Clinical and Experimental Reproductive Medicine
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• v.42 no.2
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• pp.72-76
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• 2015

$17{\alpha}$-hydroxylase and 17,20-lyase are enzymes encoded by the CYP17A1 gene and are required for the synthesis of sex steroids and cortisol. In $17{\alpha}$-hydroxylase deficiency, there are low blood levels of estrogens, androgens, and cortisol, and resultant compensatory increases in adrenocorticotrophic hormone that stimulate the production of 11-deoxycorticosterone and corticosterone. In turn, the excessive levels of mineralocorticoids lead to volume expansion and hypertension. Females with $17{\alpha}$-hydroxylase deficiency are characterized by primary amenorrhea and delayed puberty, with accompanying hypertension. Affected males usually have female external genitalia, a blind vagina, and intra-abdominal testes. The treatment of this disorder is centered on glucocorticoid and sex steroid replacement. In patients with $17{\alpha}$-hydroxylase deficiency who are being raised as females, estrogen should be supplemented, while genetically female patients with a uterus should also receive progesterone supplementation. Here, we report a case of a 21-year-old female with $17{\alpha}$-hydroxylase deficiency who had received inadequate treatment for a prolonged period of time. We also include a brief review of the recent literature on this disorder.

• Development and Reproduction
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• v.4 no.1
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• pp.109-114
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• 2000

The present study was undertaken to examine the effects of ethanol on the ovarian steroidogenic acute regulatory protein(StAR) gene expression during prepubertal and onset of puberty. From day 25, each rat began receiving either a control saline or ethanol. Animals were sacrificed on day 27 and 32, and their ovaries and blood were collected. In the present results, ethanol treatment significantly decreased serum luteinizing hormone contents at both time points. Uterine weights of ethanol-treated group were significantly lighter than control group at early time point while there was no noticeable discrepancy at late time point. Vaginal openings, a marker of onset of puberty, also clearly delayed in ethanol-treated group. Using an in situ hybridization histochemistry, we determined the expression of mRNAs encoding StAR. Ovaries from ethanol-treated rats showed a suppresed expression of StAR mRNA. These results demonstrate that ethanol can disturb the prepubertal ovarian function and onset of puberty, at least in part, through the inhibition of ovarian StAR gene expression.