Role of Estrogen and

Progesterone
They regulate HOX gene expression affecting the
development of female reproductive tract.

ESTROGEN PROGESTERONE
• Regulate HOXA10 and HOXA11 expression in
the endometrium
• In normal cycling
women, HOXA10 and HOXA11 levels increase
• In endometrial stromal cells, 17β-estradiol and
progesterone significantly
increase HOXA10 and HOXA11 expression
 Chemicals with Estrogenic Properties
• Diethylstilbestrol (DES)
- alters the localization of Hox gene expression along
the axis of the developing murine reproductive
tract, and induces developmental anomalies of
female reproductive tract
- decrease in both Hoxa10 and Hoxa11 expression
in the uterus
- complete transformation into an oviduct is
probably prevented
Xenoestrogens

• Methoxychlor (MXC)
- associated with female reproductive defects
after either prenatal or postnatal exposure
- alters Hoxa10 gene expression responsible for
normal uterine development and fertility
- expression is permanently repressed in the
uterus of mice exposed to MXC in utero
• Bisphenoyl A (BPA)
- Hoxa10 expression is increased in female mice
- contributes to the decline in female
reproductive potential and may lead to
permanent alteration of gene expression in
the adult
 HOX GENES AND INFERTILITY
• β3-integrin and Emx2/EMX2
- important for embryo implantation
- diminished HOXA10 and HOXA11 expression
in the secretory phase leads to low embryo
implantation rates
- impaired uterine receptivity lead to
infertility