The Effect of Chemotherapy Agents Doxorubicin and Cisplatin on the Developing Foetal Gonads in vivo

BACKGROUND

Cancer during pregnancy is rare, affecting about 1 in 1,000 women. Chemotherapy can be administered after the first trimester, but studies on its effects on foetal gonads are limited - concerning given the gonadotoxicity of many agents.

AIMS

The aim of this study was to assess the impact of in vivo doxorubicin (DOX) and cisplatin (CIS) treatment on:

1) germ cells using marker DDX4/MVH

2) DNA damage using marker γH2AX

3) average diameter of the seminiferous cords in the testis

4) ovarian vasculature integrity in the ovary using aSMA and H&E stained ovaries

METHODS

Standard immunofluorescence lab protocol

Standard H&E lab protocol

Analyses were performed using ImageJ

Graphs were generated with Prism 10

RESULTS

DOX-treated testes had significantly fewer germ cells than controls (p<0.013), corresponding with a reduction in average seminiferous cord diameter (p<0.011).

There was also a small, non-significant impact of CIS on testicular germ cell number.

No evidence of DNA damage in the form of double-strand breaks was found in chemotherapy-treated foetal gonads of either sex. In the chemotherapy-exposed foetal ovaries, germ cells were unaffected, but a strong trend of stromal vascular damage in the DOX-treated group was noted in the H&E experiment.

CONCLUSIONS

The study suggests that in vivo DOX exposure is likely gonadotoxic to the developing foetal mouse, primarily affecting the testis and potentially the ovary.

CIS shows a milder, testis-specific effect. Further research with larger samples is needed to confirm if these findings have the same in the human foetal gonads.