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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1125-1131
Number of pages7
JournalJournal of Endocrinological Investigation
Volume40
Issue number10
DOIs
StatePublished - 1 Oct 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017, Italian Society of Endocrinology (SIE).

Keywords

  • AMH
  • Apoptosis
  • IUGR
  • Inflammation
  • LPS
  • Ovarian reserve

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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