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IUGR induced by maternal chronic inflammation: long-term effect on offspring’s ovaries in rat model—a preliminary report

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Abstract

Purpose

Excess maternal inflammation and oxidative stress while in utero have been known to affect gross fetal development. However, an association between the inflammatory process in utero and the effects on ovarian development and future fertility has not yet been demonstrated. This study focused on LPS-induced chronic inflammation in early pregnancy and its effect on ovarian development and reserves of the offspring, using a rat model. Our aim was to determine whether maternal inflammation in utero disturbs reproductive system development in the offspring, given that maternal inflammation and oxidative stress has been shown to affect gross fetal development.

Methods

Prospective case control rat model. Sprague–Dawley pregnant rats (n = 11) received intraperitoneal lipopolysaccharide (LPS group) (50 µg/kg bodyweight) or saline solution (control group) on day 14, 16, and 18 of gestation. Pups were delivered spontaneously. At 3 months, female offspring were weighed and killed. Ovaries were harvested for (1) follicle count using hematoxylin and eosin staining, (2) apoptosis: ovaries were stained for caspase, and (3) serum CRP and AMH levels were determined.

Results

Birth weights of pups were significantly lower in the LPS group compared to the control group (6.0 ± 0.6 vs. 6.6 ± 0.4 gr; P = 0.0003). The LPS group had fewer preantral follicles, and increased intensity of Caspase 3 staining (510 vs. 155.5 u; P = 0.007). AMH levels were significantly lower in the LPS group (4.15 ± 0.46 vs 6.08 ± 1.88 ng/ml; P = 0.016). There was no significant difference in the CRP and MCP-1 levels between the two groups.

Conclusions

Chronic maternal inflammation induced intrauterine growth restriction in offspring and a decrease in the proportion of follicles. This change might be due to premature apoptosis. These preliminary results suggest that maternal inflammation has a detrimental effect on the development of the female reproductive system of the offspring and thus, future fertility.

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Authors and Affiliations

  1. IVF Unit, Department of Obstetrics and Gynecology, Hillel-Yaffe Medical Center, Hadera, Israel

    Einat Shalom-Paz, Sabrina Weill & Saja Anabusi

  2. Department of Obstetrics and Gynecology, Rambam Medical Center, Haifa, Israel

    Yuval Ginzberg, Nizar Khatib & Ron Beloosesky

  3. Department of Pathology, Rambam Medical Center, Haifa, Israel

    Geula Klorin & Edmond Sabo

  4. Ruth and Bruce Rappaport School of Medicine, The Technion – Israel Institute of Technology, Haifa, Israel

    Einat Shalom-Paz, Sabrina Weill, Yuval Ginzberg, Nizar Khatib, Saja Anabusi, Geula Klorin, Edmond Sabo & Ron Beloosesky

Authors
  1. Einat Shalom-Paz
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  2. Sabrina Weill
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  3. Yuval Ginzberg
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  4. Nizar Khatib
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  5. Saja Anabusi
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  6. Geula Klorin
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  7. Edmond Sabo
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  8. Ron Beloosesky
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Correspondence to Einat Shalom-Paz.

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All authors declare no conflict of interest.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Shalom-Paz, E., Weill, S., Ginzberg, Y. et al. IUGR induced by maternal chronic inflammation: long-term effect on offspring’s ovaries in rat model—a preliminary report. J Endocrinol Invest 40, 1125–1131 (2017). https://doi.org/10.1007/s40618-017-0681-3

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  • DOI: https://doi.org/10.1007/s40618-017-0681-3

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