GATA-like protein-1 (GLP-1) is required for normal germ cell development during embryonic oogenesis

Abstract

Oogenesis and primordial follicle formation are tightly linked processes, requiring organized and precisely timed communication between somatic and germ cells. Deviations in ovarian cell cross talk, or aberrant gene expression within one of the cell populations, can lead to follicle loss or dysfunction, resulting in infertility. Expression of GATA-like protein-1 (GLP-1) in ovarian somatic cells is required for normal fertility in female mice, as GLP-1 deficiency leads to the absence of oocytes at birth. However, the timing and nature of this germ cell loss is not well understood. In this study, we characterize the embryonic germ cell loss in GLP-1 null mice. Quantitative PCR demonstrates that ovarian Glp-1 mRNA is expressed in a bimodal pattern during embryogenesis, peaking at E13.5-14.5 and again at birth. In contrast, adult ovaries express low but detectable levels of Glp-1 mRNA. Analysis of developing GLP-1 null mouse ovaries shows that germ cells are appropriately specified and migrate normally to nascent gonads. Upon arrival at the gonad, precocious loss of germ cells begins at around E13.5. This loss is completed by birth and is accompanied by defects in the expression of genes associated with meiotic entry. Interestingly, somatic pregranulosa cells still form basement membranes surrounding germ line cysts and express mRNA encoding paracrine signaling molecules that communicate with oocytes, albeit at lower levels than normal. Together, these data imply that the somatic cell protein GLP-1 is not necessary for many pregranulosa cell functions but is required for germ cell survival.

Gonad transcriptome analysis of pearl oyster Pinctada margaritifera: identification of potential sex differentiation and sex determining genes

“…Furthermore, three genes identified as implicated in the female sex determination/differentiation pathway were found in female clusters: pmarg-foxl2 coding for the Forkhead box protein L2 (Contig_43072, cluster 7), known to be essential for ovary differentiation and maintenance, and repression of the genetic program for somatic testis determination [61]; the GATA-type zinc finger protein 1 ( zglp1 , Contig_25360, cluster 8) and the protein ovo ( ovo , Contig_8141, cluster 9), known to be involved in female germ line sex differentiation [62, 63]. These female genes presented an opposite expression profile compared to previously mentioned male genes, as shown in figure 7 for pmarg-foxl2 .…”

Polarity Protein Scrib Facilitates Endothelial Inflammatory Signaling

“…Little is known about GLP-1, although it was reported to act as transcriptional repressor of GATA factor function in somatic cells of the gonads. 22 Its function in endothelial cells, however, is completely elusive. Importantly, we readily detected GLP-1 protein in HUVEC, human fibroblasts, human dermal microvascular endothelial cells, and human aortic smooth muscle cells ( Figure IVA in the online-only Data Supplement).…”

“…GLP-1(lacZ) null mice are infertile, caused by a marked reduction in oocyte development and severe sperm differentiation defects. 22,23 Based on the similarity of GLP-1 and GATAs and on the fact that we recovered GLP-1 as Scrib-interacting protein, we focused on this factor. Scrib siRNA lowered the GLP-1 protein expression in the cytoplasm and in the nucleus.…”

Follicular Development

“…119,120 Analysis of developing Zglp1 null mouse ovaries shows that germ cells are appropriately specified and migrate normally to nascent gonads. Zglp1 is primarily expressed in the somatic cells of the developing gonads at E13.5 and granulosa cells of the adult ovaries.…”

“…Zglp1 is primarily expressed in the somatic cells of the developing gonads at E13.5 and granulosa cells of the adult ovaries. 120 Mutant mice have defects in the expression of genes associated with meiotic entry; however, it is unclear whether meiosis is perturbed and whether decreased gene expression is simply a reflection of fewer germ cells. Initial studies indicated that germ cell loss occurs as early as E17.5, at the time when oocyte meiosis is becoming arrested and prior to the formation of primordial follicles.…”