scholarly journals The role of germ cell loss during primordial follicle assembly: a review of current advances

2017 ◽  
Vol 13 (4) ◽  
pp. 449-457 ◽  
Author(s):  
Yuan-Chao Sun ◽  
Xiao-Feng Sun ◽  
Paul W. Dyce ◽  
Wei Shen ◽  
Hong Chen
Reproduction ◽  
2011 ◽  
Vol 141 (2) ◽  
pp. 173-181 ◽  
Author(s):  
Tamara J Strauss ◽  
Diego H Castrillon ◽  
Stephen R Hammes

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.


Reproduction ◽  
2009 ◽  
Vol 137 (4) ◽  
pp. 709-720 ◽  
Author(s):  
Patricia Rodrigues ◽  
Darlene Limback ◽  
Lynda K McGinnis ◽  
Carlos E Plancha ◽  
David F Albertini

In the perinatal ovary of most mammals, external and internal factors establish a primordial follicle reserve that specifies the duration of the reproductive lifespan of a given species. We analyzed the mechanism of follicle loss and survival in C57BI/6 mice using static and dynamic assays of apoptosis, autophagy, and ovarian morphogenesis. We confirm an initial loss soon after birth, when about 44% of the germ cells detectable at the end of the fetal period abruptly disappear. The observations that (1) few germ or somatic cells were apoptotic in newborn ovaries, (2) vitally stained organ cultures exhibit active extrusion of non-apoptotic germ cells and (3) germ-cell lysosome amplification occurs at birth suggested that additional mechanisms are involved in perinatal germ cell loss. Newborn mouse ovaries cultured in the pH sensitive dye lysotracker red exhibit an increased incidence of acidified non-apoptotic germ cells when maintained in the absence but not in the presence of serum, implying a role for autophagy in germ cell attrition. Inhibitors of autophagy, but not apoptosis, reduce germ cell acidification induced by serum starvation in ovary organ cultures and protein mediators of both autophagy and apoptosis are expressed at birth. From these findings we suggest that multiple perinatal mechanisms establish the primordial follicle reserve in mice.


Reproduction ◽  
2016 ◽  
Vol 151 (5) ◽  
pp. 553-562 ◽  
Author(s):  
Kavitha Vaithiyanathan ◽  
Seng H Liew ◽  
Nadeen Zerafa ◽  
Thilini Gamage ◽  
Michele Cook ◽  
...  

Abstract Apoptosis plays a prominent role during ovarian development by eliminating large numbers of germ cells from the female germ line. However, the precise mechanisms and regulatory proteins involved in germ cell death are yet to be determined. In this study, we characterised the role of the pro-apoptotic BH3-only protein, BCL2-modifying factor (BMF), in germ cell apoptosis in embryonic and neonatal mouse ovaries. BMF protein was immunohistochemically localised to germ cells at embryonic days 15.5 (E15.5) and E17.5 and postnatal day 1 (PN1), coincident with entry into the meiotic prophase, but was undetectable at E13.5, and only present at low levels at PN3 and PN5. Consistent with this expression pattern, loss of BMF in female mice was associated with a decrease in apoptosis at E15.5 and E17.5. Furthermore, increased numbers of germ cells were found in ovaries from Bmf−/− mice compared with WT animals at E15.5 and PN1. However, germ cell numbers were comparable between Bmf−/− and WT ovaries at PN3, PN5 and PN10. Collectively, these data indicate that BMF mediates foetal oocyte loss and its action limits the maximal number of germ cells attained in the developing ovary, but does not influence the number of primordial follicles initially established in ovarian reserve.


Reproduction ◽  
2014 ◽  
Vol 147 (5) ◽  
pp. 615-625 ◽  
Author(s):  
M D Baker ◽  
M Ezzati ◽  
G M Aloisio ◽  
E D Tarnawa ◽  
I Cuevas ◽  
...  

The process of germ cell development is under the tight control of various signaling pathways, among which the PI3K-Akt-mTOR pathway is of critical importance. Previous studies have demonstrated sex-specific roles for several components of this pathway. In the current study, we aimed to evaluate the role of Rheb, a member of the small GTPase superfamily and a critical component for mTORC1 activation, in male and female gametogenesis. The function of Rheb in development and the nervous system has been extensively studied, but little is known about its role in the germ line. We have exploited genetic approaches in the mouse to study the role of Rheb in the germ line and have identified an essential role in spermatogenesis. Conditional knockout (cKO) of Rheb in the male germ line resulted in severe oligoasthenoteratozoospermia and male sterility. More detailed phenotypic analyses uncovered an age-dependent meiotic progression defect combined with subsequent abnormalities in spermiogenesis as evidenced by abnormal sperm morphology. In the female, however, germ-cell specific inactivation of Rheb was not associated with any discernible abnormality; these cKO mice were fertile with morphologically unremarkable ovaries, normal primordial follicle formation, and subsequent follicle maturation. The absence of an abnormal ovarian phenotype is striking given previous studies demonstrating a critical role for the mTORC1 pathway in the maintenance of primordial follicle pool. In conclusion, our findings demonstrate an essential role of Rheb in diverse aspects of spermatogenesis but suggest the existence of functionally redundant factors that can compensate for Rheb deficiency within oocytes.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Cynthia Tang ◽  
Jimin Han ◽  
Sonal Dalvi ◽  
Kannan Manian ◽  
Lauren Winschel ◽  
...  

AbstractMutations in CLN3 lead to photoreceptor cell loss in CLN3 disease, a lysosomal storage disorder characterized by childhood-onset vision loss, neurological impairment, and premature death. However, how CLN3 mutations cause photoreceptor cell death is not known. Here, we show that CLN3 is required for phagocytosis of photoreceptor outer segment (POS) by retinal pigment epithelium (RPE) cells, a cellular process essential for photoreceptor survival. Specifically, a proportion of CLN3 in human, mouse, and iPSC-RPE cells localized to RPE microvilli, the site of POS phagocytosis. Furthermore, patient-derived CLN3 disease iPSC-RPE cells showed decreased RPE microvilli density and reduced POS binding and ingestion. Notably, POS phagocytosis defect in CLN3 disease iPSC-RPE cells could be rescued by wild-type CLN3 gene supplementation. Altogether, these results illustrate a novel role of CLN3 in regulating POS phagocytosis and suggest a contribution of primary RPE dysfunction for photoreceptor cell loss in CLN3 disease that can be targeted by gene therapy.


2016 ◽  
Vol 6 (12) ◽  
pp. 3849-3857 ◽  
Author(s):  
Dhananjay Chaturvedi ◽  
Mayu Inaba ◽  
Shane Scoggin ◽  
Michael Buszczak

Abstract Conserved from yeast to humans, the Paf1 complex participates in a number of diverse processes including transcriptional initiation and polyadenylation. This complex typically includes five proteins: Paf1, Rtf1, Cdc73, Leo1, and Ctr9. Previous efforts identified clear Drosophila homologs of Paf1, Rtf1, and Cdc73 based on sequence similarity. Further work showed that these proteins help to regulate gene expression and are required for viability. To date, a Drosophila homolog of Ctr9 has remained uncharacterized. Here, we show that the gene CG2469 encodes a functional Drosophila Ctr9 homolog. Both human and Drosophila Ctr9 localize to the nuclei of Drosophila cells and appear enriched in histone locus bodies. RNAi knockdown of Drosophila Ctr9 results in a germline stem cell loss phenotype marked by defects in the morphology of germ cell nuclei. A molecular null mutation of Drosophila Ctr9 results in lethality and a human cDNA CTR9 transgene rescues this phenotype. Clonal analysis in the ovary using this null allele reveals that loss of Drosophila Ctr9 results in a reduction of global levels of histone H3 trimethylation of lysine 4 (H3K4me3), but does not compromise the maintenance of stem cells in ovaries. Given the differences between the null mutant and RNAi knockdown phenotypes, the germ cell defects caused by RNAi likely result from the combined loss of Drosophila Ctr9 and other unidentified genes. These data provide further evidence that the function of this Paf1 complex component is conserved across species.


2017 ◽  
Vol 28 (2) ◽  
pp. 333-338 ◽  
Author(s):  
G. Mangili ◽  
C. Sigismondi ◽  
D. Lorusso ◽  
G. Cormio ◽  
M. Candiani ◽  
...  

2004 ◽  
Vol 22 (2) ◽  
Author(s):  
AnnaC. Pfannenberg ◽  
Karin Oechsle ◽  
Carsten Bokemeyer ◽  
Christian Kollmannsberger ◽  
BernhardM. Dohmen ◽  
...  

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