Chorionic somatomammotropin (CSH) is a placenta-specific hormone associated with fetal growth, and fetal and maternal metabolism in both humans and sheep. We hypothesized that CSH deficiency could impact sheep fetal liver glucose utilization. To generate CSH-deficient pregnancies, day 9 hatched blastocysts were infected with lentiviral particles expressing CSH-specific shRNA (RNAi) or scramble control shRNA (SC) and transferred to synchronized recipients. CSH RNAi generated two distinct phenotypes at 135 days of gestational age (dGA); pregnancies with IUGR (RNAi-IUGR) or with normal fetal weight (RNAi-NW). Fetal body, fetal liver and placental weights were reduced (P < 0.05) only in RNAi-IUGR pregnancies compared to SC. Umbilical artery plasma insulin and insulin-like growth factor 1 (IGF1) concentrations were decreased, whereas insulin receptor beta (INSR) concentration in fetal liver was increased (P < 0.05) in both RNAi phenotypes. The mRNA concentrations of IGF1, IGF2, IGF binding protein 2 (IGFBP2) and IGFBP3 were decreased (P < 0.05) in fetal livers from both RNAi phenotypes. Fetal liver glycogen concentration and glycogen synthase 1 (GYS1) concentration were increased (P < 0.05), whereas fetal liver phosphorylated-GYS (inactive GYS) concentration was reduced (P < 0.05) in both RNAi phenotypes. Lactate dehydrogenase B (LDHB) concentration was increased (P < 0.05) and IGF2 concentration was decreased (P < 0.05) in RNAi-IUGR fetal livers only. Our findings suggest that fetal liver glucose utilization is impacted by CSH RNAi, independent of IUGR, and is likely tied to enhanced fetal liver insulin sensitivity in both RNAi phenotypes. Determining the physiological ramifications of both phenotypes, may help to differentiate direct effect of CSH deficiency or its indirect effect through IUGR.
Asghar Ali, Callie M Swanepoel, Quinton A Winger, Paul J Rozance, and Russell V Anthony
Juliano C da Silveira, Ana Clara F C M de Ávila, Hannah L Garrett, Jason E Bruemmer, Quinton A Winger, and Gerrit J Bouma
Mammalian gamete maturation requires extensive signaling between germ cells and their surrounding somatic cells. In the ovary, theca cells, mural granulosa cells, cumulus cells and the oocyte all secrete factors throughout follicle growth and maturation that are critical for ovulation of a high-quality oocyte with the competence to develop into an embryo. Similarly, maturation of sperm occurs as it transits the epididymis during which epididymal epithelium and sperm exchange secretory factors that are required for sperm to gain motility and fertility. Recent studies in a variety of species have uncovered the presence of cell-secreted vesicles in follicular fluid (microvesicles and exosomes) and epididymal fluid (epididymosomes). Moreover, these cell-secreted vesicles contain small non-coding regulatory RNAs called microRNAs, which can be shuttled between maturing gametes and surrounding somatic cells. Although little is known about the exact mechanism of how microRNAs are loaded into these cell-secreted vesicles or are transferred and modulate gene expression and function in gametes, recent studies clearly suggest that cell-secreted vesicle microRNAs play a role in oocyte and sperm maturation. Moreover, a role for cell-secreted vesicular microRNAs in gamete maturation provides for novel opportunities to modulate and discover new diagnostic markers associated with male or female fertility. This manuscript provides an overview of cell-secreted vesicles in ovarian follicular fluid and epididymal fluid and microRNAs and discusses recent discoveries on the potential function of cell-secreted vesicles as carriers of microRNAs in oocyte and sperm maturation.