Altered germline cyst formation and oogenesis in Tex14 mutant mice

Abstract

During oocyte differentiation in mouse fetal ovaries, sister germ cells are connected by intercellular bridges, forming germline cysts. Within the cyst, primary oocytes form via gaining cytoplasm and organelles from sister germ cells through germ cell connectivity. To uncover the role of intercellular bridges in oocyte differentiation, we analyzed mutant female mice lacking testis-expressed 14 (TEX14), a protein involved in intercellular bridge formation and stabilization. In Tex14 homozygous mutant fetal ovaries, germ cells divide to form a reduced number of cysts in which germ cells remained connected via syncytia or fragmented cell membranes, rather than normal intercellular bridges. Compared with wild-type cysts, homozygous mutant cysts fragmented at a higher frequency and produced a greatly reduced number of primary oocytes with precocious cytoplasmic enrichment and enlarged volume. By contrast, Tex14 heterozygous mutant germline cysts were less fragmented and generate primary oocytes at a reduced size. Moreover, enlarged primary oocytes in homozygous mutants were used more efficiently to sustain folliculogenesis than undersized heterozygous mutant primary oocytes. Our observations directly link the nature of fetal germline cysts to oocyte differentiation and development.

Mouse oocytes develop in cysts with the help of nurse cells

“…This component of IBs was shown recently to have profound repressive effects on the kinetics of nurse cell intercellular organelle transport. In Tex14 À/À mutants, centrosome transport and Balbiani body formation is accelerated such that many E14.5 cysts already contain a Bb (Ikami et al, 2021). Tex14 may also control bridge stability.…”

“…More detailed studies confirmed that Tex14 mutation disrupts normal IB formation but found that some female cysts form and polarize. Their cyst cells compensate for the defective bridges and transfer organelles from nurse cells to oocytes through broken membranes on an accelerated schedule, suggesting that Tex14 is a transfer inhibitor (Ikami et al, 2021).…”

Uncoupling cell division and cytokinesis during germline development in metazoans

“…Tex14 mutant male mice are sterile, with seminiferous tubules containing markedly few late meiotic and post-meiotic germ cells that lack intercellular bridges ( Greenbaum et al, 2006 ). TEX14 also regulates intercellular bridges in the mouse ovary ( Ikami et al, 2021 ; Niu and Spradling, 2022 ) and mutations in Tex14 are associated with infertility in pigs and humans ( Gershoni et al, 2017 ; Sironen et al, 2017 ; Fakhro et al, 2018 ), consistent with a fundamental role for this protein in the regulation of stable intercellular bridges, at least in mammals.…”

“…The widespread occurrence of germ cell intercellular bridges implies that they play an important role in gamete production. Indeed, disruption of germ cell intercellular bridges generally leads to reduced fecundity or sterility ( Yue and Spradling, 1992 ; Xue and Cooley, 1993 ; Greenbaum et al, 2006 ; Greenbaum et al, 2009 ; Ikami et al, 2021 ). Early ultrastructural studies that provided evidence for both cytoplasmic and organelle sharing within germ cell cysts, led to three main hypotheses regarding the role of germ cell intercellular bridges.…”

Insights into in vivo follicle formation: a review of in vitro systems

“…In Tex14-null female mouse fetuses, oocytes have been shown to lack stable intracellular bridges, but the oocyte cyst structure does not disappear completely. Although it remains unclear whether cysts are essential for oogenesis in mammals, primordial follicles have been shown to form in Tex14-null mice (Ikami et al 2021). In addition, Tex14-null mice will remain fertile for over a year.…”