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Preclinical research suggests the chemotherapy drug etoposide may have adverse effects on the developing ovaries of female fetuses.
Researchers found that etoposide can damage the development of mouse ovary tissue in vitro.
However, if the drug is given after ovarian follicles have developed, the damage is not significant.
The researchers said further study is needed to assess whether etoposide has similar effects on human tissue.
“In a study involving mouse tissue, we have shown that etoposide can damage the development of the ovaries while a fetus is in the womb,” said study author Norah Spears, DPhil, of the University of Edinburgh in the UK.
“The drug affects the germ cells in the ovaries, which are the cells that give rise to eggs. This is important because it could mean that the fertility of the offspring could be affected in later life.”
Dr Spears and her colleagues reported these findings in BMC Cancer.
The researchers noted that etoposide is considered safe for use in the second and third trimester of pregnancy because it has a low risk of miscarriage and birth defects. However, little is known about the effects of the drug on the unborn baby in later life.
A woman’s reproductive lifespan is determined before birth, while the ovaries are developing in the womb. The second and third trimesters are particularly important, as that’s when female germ cells form ovarian follicles, which determine how many eggs a woman will be able to release in her lifetime.
Ovarian follicles each contain an oocyte. The process by which oocytes become enclosed in follicles starts about 17 weeks into fetal development and is only completed in late pregnancy.
Dr Spears and her colleagues found that exposing mouse ovaries to etoposide before follicles had formed caused the death of most germ cells. The few remaining germ cells went on to form unhealthy follicles. Once oocytes were enclosed in follicles, however, etoposide had no significant adverse effects.
The researchers collected fetal and neonatal ovaries from mice and cultured them in the lab. The team then exposed groups of 6 ovaries each to different doses of etoposide.
When fetal ovaries were treated with etoposide prior to follicle formation, this resulted in dose-dependent damage. Total follicle numbers declined by 72% to 90% in response to medium and high doses of etoposide, respectively.
In neonatal ovaries after follicle formation, etoposide only had minor effects, even at doses higher than those used to treat fetal ovaries.
“Our work indicates that female mouse germ cells are particularly susceptible to damage by etoposide at a specific early developmental stage, immediately prior to follicle formation, and that there could be possible consequences to the fertility of females born to women who were treated with etoposide during the second trimester of their pregnancy,” Dr Spears said.
She and her colleagues noted that additional research is needed to determine if these effects might occur in humans. And research is needed to determine whether the adverse effects of etoposide in germ cells are caused by damage to the DNA or because etoposide affects other processes such as transcription. 
Photo by Nina Matthews
Preclinical research suggests the chemotherapy drug etoposide may have adverse effects on the developing ovaries of female fetuses.
Researchers found that etoposide can damage the development of mouse ovary tissue in vitro.
However, if the drug is given after ovarian follicles have developed, the damage is not significant.
The researchers said further study is needed to assess whether etoposide has similar effects on human tissue.
“In a study involving mouse tissue, we have shown that etoposide can damage the development of the ovaries while a fetus is in the womb,” said study author Norah Spears, DPhil, of the University of Edinburgh in the UK.
“The drug affects the germ cells in the ovaries, which are the cells that give rise to eggs. This is important because it could mean that the fertility of the offspring could be affected in later life.”
Dr Spears and her colleagues reported these findings in BMC Cancer.
The researchers noted that etoposide is considered safe for use in the second and third trimester of pregnancy because it has a low risk of miscarriage and birth defects. However, little is known about the effects of the drug on the unborn baby in later life.
A woman’s reproductive lifespan is determined before birth, while the ovaries are developing in the womb. The second and third trimesters are particularly important, as that’s when female germ cells form ovarian follicles, which determine how many eggs a woman will be able to release in her lifetime.
Ovarian follicles each contain an oocyte. The process by which oocytes become enclosed in follicles starts about 17 weeks into fetal development and is only completed in late pregnancy.
Dr Spears and her colleagues found that exposing mouse ovaries to etoposide before follicles had formed caused the death of most germ cells. The few remaining germ cells went on to form unhealthy follicles. Once oocytes were enclosed in follicles, however, etoposide had no significant adverse effects.
The researchers collected fetal and neonatal ovaries from mice and cultured them in the lab. The team then exposed groups of 6 ovaries each to different doses of etoposide.
When fetal ovaries were treated with etoposide prior to follicle formation, this resulted in dose-dependent damage. Total follicle numbers declined by 72% to 90% in response to medium and high doses of etoposide, respectively.
In neonatal ovaries after follicle formation, etoposide only had minor effects, even at doses higher than those used to treat fetal ovaries.
“Our work indicates that female mouse germ cells are particularly susceptible to damage by etoposide at a specific early developmental stage, immediately prior to follicle formation, and that there could be possible consequences to the fertility of females born to women who were treated with etoposide during the second trimester of their pregnancy,” Dr Spears said.
She and her colleagues noted that additional research is needed to determine if these effects might occur in humans. And research is needed to determine whether the adverse effects of etoposide in germ cells are caused by damage to the DNA or because etoposide affects other processes such as transcription.
Photo by Nina Matthews
Preclinical research suggests the chemotherapy drug etoposide may have adverse effects on the developing ovaries of female fetuses.
Researchers found that etoposide can damage the development of mouse ovary tissue in vitro.
However, if the drug is given after ovarian follicles have developed, the damage is not significant.
The researchers said further study is needed to assess whether etoposide has similar effects on human tissue.
“In a study involving mouse tissue, we have shown that etoposide can damage the development of the ovaries while a fetus is in the womb,” said study author Norah Spears, DPhil, of the University of Edinburgh in the UK.
“The drug affects the germ cells in the ovaries, which are the cells that give rise to eggs. This is important because it could mean that the fertility of the offspring could be affected in later life.”
Dr Spears and her colleagues reported these findings in BMC Cancer.
The researchers noted that etoposide is considered safe for use in the second and third trimester of pregnancy because it has a low risk of miscarriage and birth defects. However, little is known about the effects of the drug on the unborn baby in later life.
A woman’s reproductive lifespan is determined before birth, while the ovaries are developing in the womb. The second and third trimesters are particularly important, as that’s when female germ cells form ovarian follicles, which determine how many eggs a woman will be able to release in her lifetime.
Ovarian follicles each contain an oocyte. The process by which oocytes become enclosed in follicles starts about 17 weeks into fetal development and is only completed in late pregnancy.
Dr Spears and her colleagues found that exposing mouse ovaries to etoposide before follicles had formed caused the death of most germ cells. The few remaining germ cells went on to form unhealthy follicles. Once oocytes were enclosed in follicles, however, etoposide had no significant adverse effects.
The researchers collected fetal and neonatal ovaries from mice and cultured them in the lab. The team then exposed groups of 6 ovaries each to different doses of etoposide.
When fetal ovaries were treated with etoposide prior to follicle formation, this resulted in dose-dependent damage. Total follicle numbers declined by 72% to 90% in response to medium and high doses of etoposide, respectively.
In neonatal ovaries after follicle formation, etoposide only had minor effects, even at doses higher than those used to treat fetal ovaries.
“Our work indicates that female mouse germ cells are particularly susceptible to damage by etoposide at a specific early developmental stage, immediately prior to follicle formation, and that there could be possible consequences to the fertility of females born to women who were treated with etoposide during the second trimester of their pregnancy,” Dr Spears said.
She and her colleagues noted that additional research is needed to determine if these effects might occur in humans. And research is needed to determine whether the adverse effects of etoposide in germ cells are caused by damage to the DNA or because etoposide affects other processes such as transcription.