Introduction: A low oxygen and/or nutrient supply to the fetus, resulting in intrauterine growth restriction (IUGR), can affect gonadal development of the offspring and have a potential impact on fertility. Epidemiological studies on subjects born small for gestational age (SGA), as a surrogate measure of IUGR, have reported contradictory results. Data derived from animal models of placental insufficiency are limited.
Objective and hypotheses: To investigate the effects of placental insufficiency induced by uterine artery ligation (UAL) on the postnatal rat ovary.
Methods: Sprague-Dawley rats underwent UAL at day 19 of gestation. Offspring were sacrificed at 5, 20 and 40 days post-partum (dpp), representative of infancy, childhood and peri-pubertal period. At sacrifice, ovaries were excised and weighed. One gonad per animal was fixed in 4% PFA and used for histological evaluation. Follicles were counted and classified in three sections per ovary after H&E staining. The second gonad was snap frozen in liquid nitrogen and stored at −80°C until processed for RNA extraction. Gene expression of 90 genes was analyzed by TaqMan Low Density Array. Serum AMH was measured by ELISA.
Results: A lower number of total and primordial follicles was detected in 5 and 20 dpp old IUGR animals compared to controls. The number of follicles was no longer different at 40 dpp, suggesting a compensatory reduction in the rate of the physiological follicular attrition occurring during pre-pubertal period. Furthermore, IUGR modified the expression of 23 genes involved in different cellular functions, e.g. proliferation, metabolism and angiogenesis. AMH serum levels were not significantly different in the experimental animals compared to controls, although reduced levels were noted at all ages.
Conclusions: This is the first study investigating the effects of placental insufficiency on the postnatal female gonad. The ovarian follicle pool was affected in the IUGR rats up to the pre-pubertal age, but this effect did not persist in older ages. Different genes involved in fundamental cellular processes were affected by fetal hypoxia at all ages, suggesting that long term alterations occur as a consequence of IUGR. Further analyses are needed to elucidate later effects of IUGR on ovarian function and fertility lifespan. The Authors have no financial disclosure to declare and no conflict of interest to disclose.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology