title: Impact of uteroplacental insufficiency on postnatal rat male gonad.
abstract: Prenatal events such as intrauterine growth restriction can affect gonadal development of the offspring and have an impact on reproductive health. To investigate the effects of intrauterine growth restriction induced by uterine artery ligation on the postnatal rat testis. Pregnant rats underwent uterine artery ligation at day 19 of gestation. Offspring were killed at 5, 20 and 40 days post-partum (dpp). At killing, one gonad was snap-frozen in liquid nitrogen and processed for RNA and steroid extraction. The other gonad was formalin-fixed for histology. Gene expression was analyzed by TaqMan Low-Density Array. Intratesticular testosterone, estradiol and serum gonadotrophins were measured. Thirty genes were dysregulated in intrauterine growth-restricted rats compared to controls, among which markers of Sertoli cell and Leydig cell function, cell metabolism and growth factors. Testis weights were significantly reduced at 5 and 20 dpp in intrauterine growth-restricted rats and caught-up by 40 dpp Accordingly, Sertoli cell number was significantly lower in 5 dpp intrauterine growth-restricted rats. At 20 dpp, intratesticular testosterone was significantly increased in intrauterine growth-restricted rats, whereas serum gonadotrophins were unchanged. IUGR altered the gene expression in the rat testes up to peripubertal age and reduced testis size and Sertoli cell number in neonatal age. Multiple mechanisms encompassing genetic changes and steroid production by the testis may be involved in the catch-up growth phase that restored testis size by 40 dpp Permanent consequences on organ function and gamete integrity cannot be excluded and deserve further investigations.
authors.affiliation: Department of Women's and Children's HealthPediatric Endocrinology Unit, Q2:08, Karolinska Institutet and University Hospital, Stockholm, Sweden valentina.pampanini@ki.se.
authors.forename: Valentina
authors.initials: V
authors.lastname: Pampanini
authors.affiliation: Department of Systems MedicineTor Vergata University, Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Germani
authors.affiliation: Department of Systems MedicineTor Vergata University, Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Puglianiello
authors.affiliation: Department of Women's and Children's HealthPediatric Endocrinology Unit, Q2:08, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors.forename: Jan-Bernd
authors.initials: JB
authors.lastname: Stukenborg
authors.affiliation: Department of Women's and Children's HealthPediatric Endocrinology Unit, Q2:08, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Reda
authors.affiliation: Department of Women's and Children's HealthPediatric Endocrinology Unit, Q2:08, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors.forename: Iuliia
authors.initials: I
authors.lastname: Savchuk
authors.affiliation: Department of Women's and Children's HealthPediatric Endocrinology Unit, Q2:08, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors.forename: Kristín Rós
authors.initials: KR
authors.lastname: Kjartansdóttir
authors.affiliation: Department of Women's and Children's HealthPediatric Endocrinology Unit, Q2:08, Karolinska Institutet and University Hospital, Stockholm, Sweden.|Dipartimento Pediatrico Universitario Ospedaliero 'Bambino Gesù' Children's Hospital - Tor Vergata UniversityRome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cianfarani
authors.affiliation: Department of Women's and Children's HealthPediatric Endocrinology Unit, Q2:08, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Söder
mesh_terms: D000818:Animals; D004958:Estradiol / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics / Q000378:metabolism*; D005640:Follicle Stimulating Hormone / Q000097:blood; D015870:Gene Expression; D007985:Leydig Cells / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D010927:Placental Insufficiency / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012708:Sertoli Cells / Q000378:metabolism; D013737:Testis / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism*
chemical_list: D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone
keywords: developmental origins of health and disease; intrauterine growth restriction; testis; uteroplacental insufficiency