Name: FLÁVIA CAROLINE FARIAS DOS SANTOS

Publication date: 15/03/2024

Examining board:

Namesort descending Role
JONES BERNARDES GRACELI Presidente
LEANDRO MIRANDA ALVES Examinador Externo
ROGER LYRIO DOS SANTOS Examinador Interno

Summary: Microcystin (MC) is considered the most frequent cyanobacteria toxin found in algae
blooms. Despite being previously described as hepatotoxin, some studies showed that
MC can also affect other organs, including the reproductive organs. Few studies
evaluated MC effects in the hypothalamic-pituitary-gonadal (HPG) axis. In this study,
we assessed whether MC exposure results in female metabolic and HPG axis
abnormalities. Female rats were exposed to single dose of MC at environmentally
relevant doses (5, 20 and 40 g /kg). After 24 hours, metabolic and reproductive
parameters were assessed for 15 days. No important metabolic changes were
observed after MC exposure. However, MC exposure resulted in abnormal HPG axis
function. Specifically, MC reduced hypothalamic GnRH protein expression, increased
pituitary protein expression of GnRHr and the inflammatory markers, ED1 and IL-6 and
reduced serum LH and increased FSH levels. Furthermore, MC caused irregular
estrous cyclicity and abnormal ovarian morphophysiology, such as reduced primary
follicles, increased corpora lutea, increased anti-Müllerian hormone (AMH) and
progesterone (P4) levels, and reduced estrogen (E2) levels. MC changed ovarian
protein expression makers, leading to increased VEGFr (angiogenesis), FSHr and LHr
(gonadotropin receptor), AMH (ovarian reserve), ED1 and IL-6 (inflammation), Gp91-
phox (oxidative stress) and reduced ER (steroid receptor). Blunted estrogen negative
feedback was observed in MC rats after ovariectomy, showing no significant changes
in LH levels compared to intact MC rats. Thus, these data suggest that single MC
exposure leads to abnormal control of HPG axis function at different levels in female
rats.

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