Thesis (Ph. D.)--University of Chicago, Dept. of Organismal Biology and Anatomy, December 2000. / Includes bibliographical references. Also available on the Internet.

Thesis (doctoral)--Ludwig Maximilians-Universität zu München, 1979.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1969. / Typescript. Vita. Includes bibliographical references.

Thesis (doctoral)--Ludwig Maximilians-Universität zu München, 1979.

Thesis (M.A.)--Rowan University, 2009. / Typescript. Includes bibliographical references.

Thesis (Ph. D.)--Ohio State University, 2005. / Title from first page of PDF file. Document formatted into pages; contains xvii, 181 p. : ill. Includes bibliographical references (p. 159-181). Available online via OhioLINK's ETD Center

Made available in DSpace on 2014-06-11T19:23:00Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-23Bitstream added on 2014-06-13T19:28:46Z : No. of bitstreams: 1 silva_ds_me_botib.pdf: 411709 bytes, checksum: 1274000fd98416a831be271d8963c9a7 (MD5) / A puberdade constitui um período de rápidas e interativas alterações morfológicas, endócrinas e comportamentais. Atualmente a exposição à contaminantes ambientais tem sido implicada como um dos fatores responsáveis por alterações no desenvolvimento infantil, resultando em precocidade ou atraso na puberdade. Numerosos compostos químicos de uso doméstico, industrial e agrícola possuem comprovada atividade hormonal, sendo conhecidos com desreguladores endócrinos. Alguns clínicos estão começando a avaliar alguns parâmetros relacionados à interferência desses compostos no desenvolvimento de crianças residentes em áreas contaminadas, mas não há estudos correlacionando o atraso na puberdade masculina com possíveis alterações do trato reprodutivo e fertilidade a partir da maturidade sexual. Esse estudo objetivou investigar se o retardo na instalação da puberdade masculina compromete parâmetros reprodutivos na puberdade e as possíveis repercussões na fertilidade na vida adulta, utilizando o rato como modelo experimental. Tendo em vista ainda que na literatura existe um grande intervalo fixado para o início da puberdade, o trabalho pretendeu também analisar os parâmetros de puberdade do rato normal, contribuindo para o estabelecimento de uma idade real para a puberdade de ratos machos Wistar. Para tanto, foi provocado um atraso no início da puberdade mediante administração de dose alta de dibutil ftalato (DBP) durante o período fetal. Foram avaliados parâmetros morfofuncionais do trato reprodutivo masculino, dosagens hormonais, avaliações espermáticas, além de análises histopatológicas e morfométricas do testículo e epidídimo. Na puberdade, houve diminuição significativa do peso da próstata dos animais expostos ao DBP, além de redução da produção diária de espermatozóides... / Puberty is a period of fast and interactive morphological, endocrine and behavioral changes. Currently, the exposure to environmental contaminants is considered one of the factors responsible for alterations in child development, resulting in pubertal precocity or delay. Many chemical compounds with domestic, industrial and agricultural use, known as endocrine disruptors, have shown hormonal activity. Some clinicians are beginning to evaluate some parameters related to the interference of these compounds in the development of children living in contaminated areas, but there are no studies correlating this delay on puberty with possible changes in the reproductive tract and fertility from sexual maturity. This study aimed to investigate whether a delay in puberty installation affects reproductive parameters in pubertal and adult male rats. Especially considering that the literature shows a wide range fixed for the beginning of puberty, the study also intended to analyze the parameters of puberty in normal rats, contributing to the establishment of an actual age for puberty in male Wistar rats. The onset of puberty was delayed through administration of a high doses of dibutyl phthalate (DBP) during the fetal period. We assessed morphofunctional parameters of the male reproductive tract, hormonal levels, sperm evaluations, and histopathologic and morphometric analysis of testis and epididymis. At puberty, the prostate weight of DBP-exposed animals was significantly reduced. The daily sperm production was reduced in the testis of the pubertal DBP-exposed rats, and this alteration remained in the adult rats. However, neither sperm morphology nor sperm motility was altered, as well as the capacity of fertilization assessed by AI. The histopathology of testis revealed a high number of tubules with... (Complete abstract click electronic access below)

Puberty is a critical period of development that is characterized by significant remodeling and reorganization of neuronal connections. Additionally, this period is marked by the transition to a fertile state and the development of secondary sex characteristics driven by a surge in gonadal steroid hormones. Puberty is also vulnerable to stress exposure, as pubertal stress during this period results in negative enduring changes to the brain and behavior. Treatment with the bacterial endotoxin lipopolysaccharide (LPS) results in enduring dysfunction of the hypothalamic-pituitary-gonadal (HPG) axis in male and female mice. However, the mechanism underlying this dysfunction was unclear. Thus, this thesis was designed to investigate possible mechanisms through which pubertal stress could alter HPG axis functioning. This work first examined the acute effects of LPS treatment on various components of the HPG axis, such as kisspeptin (Kiss1) and kisspeptin receptor (Kiss1R) expressions in the brain, and luteinizing (LH) and follicle stimulating hormone (FSH) concentrations in the blood (Study 1). The next study examined the enduring effects of LPS treatment on inflammation as well as on Kiss1 and Kiss1R expressions in the brain, and LH and FSH concentrations in the blood (Study 2). The findings showed that Kiss1 and Kiss1R were downregulated in an acute and enduring manner following LPS treatment and are likely responsible for HPG axis downregulation. The final study amalgamates the novel discoveries of the previous findings and hypothesizes that pharmaceutical Kiss1 treatment will prevent adult sexual behavior dysfunction after pubertal LPS treatment. Findings from this study will inform us whether the enduring HPG axis downregulation following pubertal LPS treatment is reversible in adulthood and could provide a viable prospective intervention for fertility complications across species.

BACKGROUND: Kisspeptin has recently been deemed the critical central regulatory factor for gonadotropin releasing hormone (GnRH) release. Through the control of GnRH release, kisspeptin is also responsible for the secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH), both downstream and regulated by GnRH. Kisspeptin is released from kisspeptin, neurokinin B, dynorphin A (KNDy) neurons within the hypothalamus’ arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV). As the most prominent regulator of GnRH release, KNDy neurons directly influence the hypothalamic pituitary gonadal (HPG) axis. The HPG axis primarily regulates reproduction and can be inhibited by the presence of stress hormones, glucocorticoids (GCs), and activation of the hypothalamic pituitary adrenal cortex (HPA) axis. It was found that exposure to stress before and during puberty can lead to short-term pubertal delay and long-term physiological and behavioral alterations. It is known that a large portion of kisspeptin neurons contain glucocorticoid receptors (GR) which bind GCs. However, the exact pathway that allows HPA axis activation to inhibit the HPG axis is still unknown. OBJECTIVE: The objective of this study is to understand how kisspeptin neurons mediate the relationship between the HPG and HPA axis and if the lack of GR from kisspeptin neurons alters pubertal development. METHODS: A mouse model with the targeted deletion of GR from Kiss1 expressing neurons GRflox/flox; Kiss1-Cre (Kiss1GRKO) was compared to control (GRflox/flox) mice in phenotypic pubertal development studies. To determine if the removal of GR from Kiss1 expressing neurons affected pubertal development we began data recording of male and female mice phenotypes beginning on postnatal day (PND) twenty-one after weaning. We collected data assessing the body weight of the animal and age and body weight of preputial separation (PS), vaginal opening (VO), and first estrus, markers of pubertal development in mice. RESULTS: The removal of GR from Kiss1 expressing neurons did not cause a significant difference in pubertal development. Male and female Kiss1GRKO and GRflox/flox mice did not have significantly different ages or body weights at PS or VO, nor was age and body weight significantly altered at first estrus. CONCLUSION: The removal of GR and therefore the loss of the ability for Kiss1 expressing neurons to bind GCs does not appear to significantly alter pubertal development in male and female Kiss1GRKO mice. Further research and studies are necessary to determine if GR in kisspeptin neurons mediate the effects of stress on pubertal development.

This research was conducted to elucidate age-, puberty-, and sex-related effects on immunological changes in response to acute exercise. Compared with young men, 9-and 10-yr-old boys experienced smaller natural killer (NK) cell and interleukin-6 (IL-6) changes and a faster neutrophil and IL-6 recovery in response to exercise (Chapter 3). In these boys, exercise-induced neutrophil and NK cell changes were also more sensitive to carbohydrate (CHO) intake. The possible interaction of puberty and CHO intake on NK cell responses to exercise was then investigated in boys at the same chronological age (Chapter 4 ). The magnitude of change in NK cells was greatest in boys at advanced stages of puberty, and responses to CHO intake were most sensitive in prepubertal boys. To further investigate age-, puberty-, and sex-related differences in leukocyte and cytokine responses to exercise, boys and girls ages 12 and 14 were studied (Chapter 5). Neutrophil, lymphocyte, NK cell, and IL-6 responses were more pronounced in 14-yr-old versus 12-yr-old and in mid-versus early-pubertal girls. Age-and puberty-related differences in neutrophil recovery were also observed in the boys. Sex differences (girls> boys) in lymphocytes and NK cells were observed among 14-yr-old, but not 12-yr-old and among mid-, but not late-pubertal subjects. Finally, the effects of sex, menstrual phase (MP) and oral contraceptive (OC) use on leukocyte and IL-6 responses to exercise were studied in adults (Chapter 6). Compared with men, women experienced larger increases in lymphocytes, but MP did not influence immune changes. A novel observation was that OC use increased the magnitude of exercise-induced changes in leukocyte subsets. Collectively, the studies in this thesis represent the first comprehensive examination of age-, puberty-, and sex-related effects on immunological changes in response to exercise and provide the first reports of immune-related responses to CHO intake during exercise in children. / Thesis / Doctor of Philosophy (PhD)