Newborn hormone exposure can disrupt female reproductive health, rat study finds.

Sotomayor-Zárate R, M Tiszavari, G Cruz and HE Lara. 2011. Neonatal exposure to single doses of estradiol or testosterone programs ovarian follicular development-modified hypothalamic neurotransmitters and causes polycystic ovary during adulthood in the rat. Fertility and Sterility http://dx.doi.org/10.1016/j.fertnstert.2011.09.011.

A single hormone treatment given to newborn female rats significantly changed the chemical activity in the brain region that guides ovary development and function, report researchers in the journal Fertility and Sterility.

The hormones impacted two important parts of reproduction. First, the one-time treatment of either estrogen or testosterone permanently altered the way the ovaries – the follicles in particular – developed. The changes seen in the rats are similar to those in women with polycystic ovary syndrome (PCOS).

Second, the hormones altered levels of specific neurotransmitters – the brain's chemical messages sent between nerve cells. These changes were observed in regions of the brain that control reproductive functioning. Therefore, the hormones may have permanently modified the brain's control of female cycles and successful ovulation later in life – changes that may affect lifelong reproduction and fertility.

The study is important because it expands on growing concerns that early-life exposures to hormonally active chemicals may impact and alter female reproductive development and fertility. It shows that improper hormone exposures affect both ovary and brain development, possibly leading to complex health impacts later in life that are not easily tied to young-life exposures.

Control of female reproduction is regulated by interplay between specific brain regions and the ovaries. As adults, the brain cells stimulate the production of appropriately timed hormone messages that signal the ovary to produce and ovulate eggs. If either of the systems is altered, reproduction can be reduced or extinguished.

Previous studies show that improper hormone exposure in rats during the crucial time immediately after birth results in big changes: irregular reproductive cycles, ovarian malformations and decreased fertility.

The current study goes further by investigating the role of brain signals – specifically, neurotransmitter levels – on ovarian development in newborn rats treated with hormones.

To look into this, researchers treated female rats within 12 hours of birth with a one-time injection of either an estrogen (estradiol) or an androgen (testosterone). This treatment time corresponds to when rat ovarian follicles – the egg and associated ovary cells that nurture its maturation – develop. The same period occurs before birth in people.

After 60 days, the researchers examined the adult rat brains and ovaries for differences from untreated rats. They also compared differences in ovary structure and levels of brain neurotransmitters – serotonin, dopamine, noradrenalin and glutamic acid – between the estradiol- and testosterone-exposed rats.

The observed changes depended on the hormone given. While estrogen and testosterone affected the ovaries in similar ways, their effects on brain signaling differed.

Animals treated with estradiol or testosterone showed similar ovary malformations. They found reduced numbers of immature follicles, less evidence of previous ovulations and numerous, fluid-filled follicular cysts similar to those found in women with polycystic ovaries. In PCOS, an imbalance of a woman's female sex hormones contributes to health issues, including changes in the menstrual cycle, small cysts in the ovaries and trouble getting pregnant.

Further, treated rats showed differences as adults in neurotransmitter levels within brain areas that produce regulatory hormones critical for normal reproductive functioning. Estradiol increased levels of serotonin, dopamine, noradrenalin and glutamic acid, while testosterone treatment increased glutamic acid and decreased serotonin levels. The authors predict that these changes may be maintained throughout adult life, permanently modifying the brain's control of female cycles and successful ovulation.

The results suggest that females exposed to either estradiol or testosterone at the time the ovaries are developing may have permanent abnormalities that could result in reproductive problems. The exposures also produced equally permanent, but different alterations to the reproductive centers of the female brain.

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