Maternal undernutrition induces premature reproductive senescence in adult female rat offspring

An adverse uterine nutritional environment during pregnancy results in premature reproductive senescence in adult rats.

Omid Khorram, M.D., Ph.D., Erin Keen-Rinehart, Ph.D., Tsai-Der Chuang, Ph.D., Michael G. Ross, M.D., Mina Desai, Ph.D.

Volume 103, Issue 1, Pages 291-299


To determine the effects of maternal undernutrition (MUN) on the reproductive axis of aging offspring.

Animal (rat) study.

Research laboratory.

Female Sprague-Dawley rats.

Food restriction during the second half of pregnancy in rats.

Main Outcome Measure(s):
Circulating gonadotropins, antimüllerian hormone (AMH), ovarian morphology, estrous cyclicity, and gene expression studies in the hypothalamus and ovary in 1-day-old (P1) and aging adult offspring.

Offspring of MUN dams had low birth weight (LBW) and by adult age developed obesity. In addition, 80% of adult LBW offspring had disruption of estrous cycle by 8 months of age, with the majority of animals in persistent estrous. Ovarian morphology was consistent with acyclicity, with ovaries exhibiting large cystic structures and reduced corpora lutea. There was an elevation in circulating T, increased ovarian expression of enzymes involved in androgen synthesis, an increase in plasma LH/FSH levels, a reduction in E2 levels, and no changes in AMH in adult LBW offspring compared with in control offspring. Hypothalamic expression of leptin receptor (ObRb), estrogen receptor-α (ER-α), and GnRH protein was altered in an age-dependent manner with increased ObRb and ER-α expression in P1 LBW hypothalami and a reversal of this expression pattern in adult LBW hypothalami.

Our data indicate that the maternal nutritional environment programs the reproductive potential of the offspring through alteration of the hypothalamic-pituitary-gonadal axis. The premature reproductive senescence in LBW offspring could be secondary to the development of obesity and hyperleptinemia in these animals in adult life.

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