Exposição intrauterina e lactacional a doses suprafisiológicas de manganês: estudo de toxicidade reprodutiva na prole feminina de ratas
Data
2023-10-26
Autores
Correia, Maria Helena 
Orientadores
Le Sueur-Maluf, Luciana
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
O manganês (Mn) é um elemento presente naturalmente no ambiente, podendo ser
encontrado no ar, água, solo e alimentos. Exposição a concentrações elevadas de Mn pode ocorrer
por meio de fungicidas agrícolas, emissões atmosféricas industriais, sistemas de drenagem e
vazamentos, resultando em problemas pulmonares, renais e neurológicos. Estudos sobre os efeitos
de altas doses de Mn na saúde reprodutiva de animais, especialmente durante a gestação e lactação
maternas, são escassos. Assim, este estudo avaliou o efeito da exposição intrauterina e lactacional a
altas doses de Mn sobre os parâmetros reprodutivos da prole feminina de ratas. Ratas Wistar
prenhes foram distribuídas aleatoriamente em 3 grupos (n=10/grupo): grupo Mn 9mg (exposto a 9
mg de MnCl2/Kg/dia por gavage) do dia gestacional 13 (DG 13) ao dia lactacional 15 (DL 15);
grupo Mn 90 mg (exposto a 90 mg de MnCl2/Kg/dia no mesmo período e mesma via); e grupo
controle (CTRL, que recebeu apenas água destilada no mesmo período e mesma via). A prole
feminina foi avaliada, quanto à morfologia ovariana, uterina, instalação da puberdade, ciclo estral e
presença de mal formações em três estágios da vida pós-natal (n=10/grupo/idade): período prépúbere (dia pós-natal 21 - DPN 21); período puberal (DPN 25 a 35) e na fase adulta (DPN 60). A
análise comparativa entre os grupos foi realizada usando o Modelo Linear Generalizado (GzLM).
No DPN 21, não houve diferença significativa entre os grupos quanto ao número de folículos
primordiais, primários e pré-antrais. No útero, foi observado aumento da altura do epitélio luminal
e da espessura do endométrio no grupo Mn 9 mg e diminuição da espessura do miométrio no grupo
Mn 90 mg. No DPN 25-35 não houve diferença significativa entre os grupos na idade de instalação
da puberdade, mas aumento no número de folículos primordiais no grupo Mn 9 mg, folículos préantrais no grupo Mn 90 mg, e aumento de folículos atrésicos e corpos lúteos em ambos os grupos.
No útero houve diminuição da espessura do miométrio no grupo Mn 9 mg, com aumento na altura
do epitélio e redução da quantidade de glândulas no grupo Mn 90 mg. No DPN 60, no útero,
redução da espessura do endométrio e quantidade de glandulas, além de diminuição na altura do
epitélio luminal. No grupo Mn 90 mg, houve aumento na espessura do endométrio, na quantidade
de glândulas e na espessura do miométrio. O ciclo estral nesse grupo apresentou aumento na
frequência de estros e redução de diestros, resultando em mais ciclos e de menor duração. Em
conclusão, nossos achados sugerem que a exposição materna a altos níveis de Mn durante a
gestação e lactação prejudica o processo de seleção e resposta folicular da prole, que pode ser
observado desde a puberdade até a idade adulta, com impacto sobre a fisiologia uterina e a
regularidade do ciclo estral, sem afetar o momento do início da puberdade.
Manganese (Mn) is a natural environment-occurring element found in air, water, soil, and food. Exposure to elevated concentrations of Mn can occur through agricultural fungicides, atmospheric emissions, drainage, and leaks, resulting in pulmonary, renal, and neurological issues. Studies on the effects of high Mn doses on the reproductive health of animals, especially maternal pregnancy and lactation, are limited. Therefore, this study evaluated the impact of intrauterine and lactational exposure to high Mn doses on the reproductive parameters of female offspring. Pregnant Wistar rats were randomly assigned to three groups (n=10/group): the Mn 9mg group (exposed to 9 mg of MnCl2/kg/day by gavage) from gestational day 13 (GD 13) to lactational day 15 (LD 15); the Mn 90mg group (exposed to 90 mg of MnCl2/kg/day during the same period); and the control group (CTRL, which received only distilled water during the same period). Female offspring were assessed for ovarian and uterine morphology at three postnatal life stages (n=10/group/age): the prepubertal period (postnatal day 21 - PND 21); the pubertal period (PND 25 to 35); and adulthood (PND 60). Comparative analysis between groups was conducted using the Generalized Linear Model (GzLM). At PND 21, there were no significant differences among the groups regarding the number of primordial, primary, and pre-antral follicles. In the uterus, an increase in luminal epithelium height and endometrial thickness was observed in the Mn 9 mg group, while myometrial thickness decreased in the Mn 90 mg group. At PND 25-35, there were no significant differences between the groups in the onset of puberty, but an increase in primordial follicles in the Mn 9 mg group, pre-antral follicles in the Mn 90 mg group, and an increase in atretic follicles and corpus luteum in both groups. In the uterus, myometrial thickness decreased in the Mn 9 mg group, with an increase in epithelial height and a decrease in the number of glands in the Mn 90 mg group. At PND 60, the Mn 9 mg group exhibited fewer antral follicles and a reduction in endometrial thickness and the number of glands in the uterus, along with a decrease in luminal epithelium height. In the Mn 90 mg group, there was an increase in endometrial thickness, the number of glands, and myometrial thickness. The estrous cycle in this group showed an increase in the frequency of estrus and a decrease in diestrus, resulting in more cycles of shorter duration. In conclusion, our findings suggest that maternal exposure to high levels of Mn during pregnancy and lactation impairs the follicular selection and response process in the offspring, which can be observed from puberty to adulthood, with an impact on uterine physiology and estrous cycle regularity, without affecting the timing of puberty onset.
Manganese (Mn) is a natural environment-occurring element found in air, water, soil, and food. Exposure to elevated concentrations of Mn can occur through agricultural fungicides, atmospheric emissions, drainage, and leaks, resulting in pulmonary, renal, and neurological issues. Studies on the effects of high Mn doses on the reproductive health of animals, especially maternal pregnancy and lactation, are limited. Therefore, this study evaluated the impact of intrauterine and lactational exposure to high Mn doses on the reproductive parameters of female offspring. Pregnant Wistar rats were randomly assigned to three groups (n=10/group): the Mn 9mg group (exposed to 9 mg of MnCl2/kg/day by gavage) from gestational day 13 (GD 13) to lactational day 15 (LD 15); the Mn 90mg group (exposed to 90 mg of MnCl2/kg/day during the same period); and the control group (CTRL, which received only distilled water during the same period). Female offspring were assessed for ovarian and uterine morphology at three postnatal life stages (n=10/group/age): the prepubertal period (postnatal day 21 - PND 21); the pubertal period (PND 25 to 35); and adulthood (PND 60). Comparative analysis between groups was conducted using the Generalized Linear Model (GzLM). At PND 21, there were no significant differences among the groups regarding the number of primordial, primary, and pre-antral follicles. In the uterus, an increase in luminal epithelium height and endometrial thickness was observed in the Mn 9 mg group, while myometrial thickness decreased in the Mn 90 mg group. At PND 25-35, there were no significant differences between the groups in the onset of puberty, but an increase in primordial follicles in the Mn 9 mg group, pre-antral follicles in the Mn 90 mg group, and an increase in atretic follicles and corpus luteum in both groups. In the uterus, myometrial thickness decreased in the Mn 9 mg group, with an increase in epithelial height and a decrease in the number of glands in the Mn 90 mg group. At PND 60, the Mn 9 mg group exhibited fewer antral follicles and a reduction in endometrial thickness and the number of glands in the uterus, along with a decrease in luminal epithelium height. In the Mn 90 mg group, there was an increase in endometrial thickness, the number of glands, and myometrial thickness. The estrous cycle in this group showed an increase in the frequency of estrus and a decrease in diestrus, resulting in more cycles of shorter duration. In conclusion, our findings suggest that maternal exposure to high levels of Mn during pregnancy and lactation impairs the follicular selection and response process in the offspring, which can be observed from puberty to adulthood, with an impact on uterine physiology and estrous cycle regularity, without affecting the timing of puberty onset.
Descrição
Citação
CORREIA, Maria Helena. Exposição intrauterina e lactacional a doses suprafisiológicas de manganês: estudo de toxicidade reprodutiva na prole feminina de ratas. 2023. 58 f. Dissertação (Mestrado Interdisciplinar em Ciências da Saúde) - Universidade Federal de São Paulo, Instituto de Saúde e Sociedade, Santos, 2023.