The development of clear-cell adenocarcinoma of the vagina in female offspring has been strongly linked to prenatal exposure to Diethylstilbestrol (DES).

Diethylstilbestrol (DES) is a synthetic estrogen that was prescribed to pregnant women between the 1940s and 1970s to prevent miscarriages and other pregnancy complications. However, it was later discovered that in utero exposure to DES causes a variety of reproductive tract abnormalities in the female offspring, including an increased risk of clear-cell adenocarcinoma of the vagina and cervix, particularly during adolescence and young adulthood.

Key points to remember:

- DES is a synthetic nonsteroidal estrogen.
- Exposure occurs prenatally when the mother takes DES during pregnancy.
- It causes structural vaginal and cervical abnormalities such as a T-shaped uterus, vaginal adenosis, and cervical hypoplasia.
- The most significant long-term risk is the development of clear-cell adenocarcinoma of the vagina, typically diagnosed in young women aged 15-30 years.
- Other prenatal exposures listed, such as Methotrexate, Prednisolone, or Oxytocin, are not associated with vaginal clear-cell adenocarcinoma.

Thus, the correct answer is Diethylstilbestrol (DES).

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th Edition, Chapter on Female Genital Tract Tumors / Page 1054