ESPE Abstracts (2016) 86 P-P1-340

Intrauterine Growth Restriction Affects Postnatal Testis Maturation in Rats

Valentina Pampaninia, Daniela Germanib, Antonella Puglianiellob, Jan-Bernd Stukenborga, Ahmed Redaa, Iuliia Savchuka, Ros Kjartansdóttird, Stefano Cianfarania,c & Olle Södera


aDepartment of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden; bDepartment of Systems Medicine, Tor Vergata University, Rome, Italy; cDipartimento Pediatrico Universitario Ospedaliero, “Bambino Gesù” Children’s Hospital – Tor Vergata University, Rome, Italy; dCentre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark


Background: The influence of intrauterine life on long term health is supported by a wealth of epidemiological and experimental studies. A low oxygen and/or nutrient supply to the fetus, resulting in intrauterine growth restriction (IUGR), may affect gonadal development of the offspring, with a potential impact on fertility. Data derived from animal models of placental insufficiency are very limited.

Objective and hypotheses: To investigate the effects of placental insufficiency induced by uterine artery ligation (UAL) on postnatal rat testis gene expression and testosterone production.

Method: Sprague-Dawley pregnant female rats underwent UAL at day 19 of gestation to generate IUGR offspring, while sham operation was performed for the controls. Offspring were sacrificed at 5, 20 and 40 days post-partum (dpp). At sacrifice, testes were excised and weighed. Gene expression was analyzed by TaqMan® Low Density Array (TLDA). Intratesticular testosterone (ITT) and serum gonadotrophins were assessed by ELISA.

Results: Testis weights normalized to body weights were significantly reduced at 5 dpp and 20 dpp in IUGR rats, with catch-up at 40 dpp. The expression of 30 genes among the 90 investigated, involved in regulation of cell cycle, metabolism, angiogenesis, and markers of testicular somatic and germ cells, was dysregulated in IUGR rat testis compared to controls at all time points. At 20 dpp ITT was significantly increased in IUGR rats, whereas serum gonadotrophins levels were comparable between the two groups.

Conclusion: Different genes involved in fundamental processes within the testis were affected by fetal hypoxia up to pubertal age, suggesting that long term alterations occur as a consequence of IUGR. Moreover, testosterone production was increased in the pre-pubertal rats, as putative catch-up growth mechanism. Further analyses are needed to elucidate later consequences of IUGR on testis function.

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