Publications by Melanie K Stewart

Publications by authors named "Melanie K Stewart"

Ecotoxicol Environ Saf

February 2023

Endocrine disrupting chemicals (EDCs) can disrupt hormone signaling, particularly affecting developmental processes in aquatic wildlife, such as zebrafish.
The study examined the effects of varying concentrations of the synthetic estrogen 17α-ethinylestradiol (EE2) on zebrafish larvae and juveniles, revealing changes in craniofacial morphology even at low, environmentally relevant levels.
Findings indicate that the timing of exposure to EDCs significantly influences developmental outcomes, highlighting the potential risks of such chemicals to vertebrate craniofacial development, including mammals.

Int J Mol Sci

September 2021

Sex determination in vertebrates involves a switch between ovary and testis development, with oestrogen having a crucial role in non-mammals and the testis-determining gene taking precedence in mammals.
Exogenous oestrogen can change the development path of gonadal cells by limiting the effects of SOX9, a key factor promoting testis development, while activating β-catenin, which is essential for ovarian development.
The study highlights the MAPK pathway's involvement in this process, revealing that oestrogen activates β-catenin quickly and alters the balance of testis and ovary factors, shedding light on how oestrogen exposure influences gonad development.

Exp Cell Res

January 2021

Nuclear SOX9 is crucial for Sertoli cell differentiation and testis development, whereas exposure to oestrogen causes SOX9 to be retained in the cytoplasm, hindering testis formation and fostering ovarian development.
Oestrogen stabilizes microtubules and activates the ERK1/2 MAPK complex, which is essential for SOX9's localization and function.
Blocking ERK1/2 with the inhibitor U0126 prevents oestrogen's effects, highlighting a new mechanism by which oestrogen affects MAPK signaling and thereby disrupts Sertoli cell differentiation by controlling SOX9 availability.

Int J Mol Sci

November 2020

The rise of conditions related to testicular dysgenesis syndrome and decreasing human fertility are attributed to exposure to estrogenic endocrine disrupting chemicals (EDCs) in the environment.
EDCs can activate estrogen signaling in gonads, affecting the development and function of testes and ovaries, with estrogen being critical for maintaining ovarian characteristics in mammals.
The review examines how exogenous estrogen impacts the differentiation of gonadal somatic cells and the significance of understanding these processes for assessing the effects of EDCs on reproductive health.

BMC Mol Cell Biol

September 2020

The study investigates the effects of estrogen on male reproductive health by examining its influence on human testis-derived cells (NT2/D1) and the key markers involved in cell development.
Results showed that estrogen activates its receptor and leads to increased SOX9 levels initially, but causes a significant reduction in key Sertoli cell gene expression over time.
These findings suggest a long-standing impact of estrogen on gonadal cell fate in mammals, potentially contributing to the decline in male fertility observed in recent years due to exposure to endocrine disruptors.

Biol Reprod

December 2018

Exposure to estrogenic endocrine disrupting chemicals (EDCs) during fetal development is linked to increased sexual development disorders, including hypospadias, which affects urethra placement in both males and females.
This study investigated the effects of the synthetic estrogen diethylstilbestrol on male and female mice exposed in utero to both high and low doses.
Findings revealed significant reductions in anogenital distance and high rates of hypospadias in males, while females showed similar issues, confirming that even low doses of EDCs can disrupt sexual development in mice.