Activin A Accelerates the Progression of Fetal Oocytes Throughout Meiosis and Early Oogenesis in the Mouse

Abstract

Activins can exert several roles in ovary development. However, little is known about their involvement in early mammalian oogenesis. In this study, we reported that activin receptors (including ActRIA, ActRIB, ActRIIA, and ActRIIB) are expressed throughout the development of the mouse ovaries from 12.5 days postcoitum (dpc) to 21 days postparturition (dpp). Moreover, we found that in vitro, the addition of activin A (ActA) to the culture medium of 12.5 dpc ovarian tissues accelerated the progression of oocytes throughout meiotic prophase I stages. This result was reproduced in vivo following administration of ActA to pregnant mice. The in vitro effect of ActA was associated with increased expression of premeiotic and meiotic genes (including Dazl, Spo11, Stra8, Scp3, and Rec8) in the ovarian tissues. Mechanistically, ActA-dependent SMAD3 signaling modulated the expression of members of the retinoic acid (RA) system, including the RA degradation CYP26B1 enzyme and the RA receptors. Finally, ActA promoted the survival and growth of fetal and early postnatal oocytes and primordial follicle assembly both in vitro and in vivo. In conclusion, the present study identifies new roles of ActA in early oogenesis and suggested that ActA and RA might cooperate in promoting meiosis in female germ cells.

Protective effects of melatonin against nicotine-induced disorder of mouse early folliculogenesis

“…Counterstaining was performed with Hoechst33342 (Beyotime, C1022) or PI (Solarbio, P8080). Oocytes were distinguished from somatic cells for their positivity to the germ cell specific protein MVH (mouse vasa homolog) and follicles classified according to Liang’s paper [ 67 ].…”

MicroRNA dynamics at the onset of primordial germ and somatic cell sex differentiation during mouse embryonic gonad development

“…Interestingly, fetal gonads at E12.5 start to express activin and activin receptors in a sexdependent manner (Feijen et al 1994) and fetal ovaries at the same developmental stage strongly down-regulate Cyp26b1 expression (Bowles et al 2006). Moreover, the addition of activin to cultured E12.5 ovaries enhanced PGC progression throughout meiotic prophase I (Liang et al 2015). These data suggest that inhibition of some members of the activin pathway by miRNAs in male somatic cells may potentiate the expression of Cyp26b1 and promote male fate.…”

Effects of activin A on the transcriptome of mouse oogenesis in vitro

“…In previous studies, using an in vitro culture system for mouse embryonic ovaries suitable for reproducing crucial processes of early oogenesis (Morohaku et al, 2016;Obata et al, 2002;Shen et al, 2006), we found evidence that ActA is able to positively influence oocyte survival and growth, genomic imprinting, and the oocyte capability to progress through MPI stages and form primordial follicles (Liang et al, 2015;Zhang et al, 2012). (Liang et al, 2015).…”