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.

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Authors

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

Abstract

Objective:

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

Design:

Animal (rat) study.

Setting:

Research laboratory.

Animal(s):

Female Sprague-Dawley rats.

Intervention(s):

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.

Result(s):

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.

Conclusion(s):

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.

Authors:

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

Abstract:

Objective:

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

Design:

Animal (rat) study.

Setting:

Research laboratory.

Animal(s):

Female Sprague-Dawley rats.

Intervention(s):

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.

Result(s):

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.

Conclusion(s):

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.

Read the full text at: http://www.fertstert.org/article/S0015-0282(14)02203-1/fulltext


Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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