scholarly journals The developing ovary of the South American plains vizcacha, Lagostomus maximus (Mammalia, Rodentia): massive proliferation with no sign of apoptosis-mediated germ cell attrition

Reproduction ◽  
2011 ◽  
Vol 141 (5) ◽  
pp. 633-641 ◽  
Author(s):  
N P Leopardo ◽  
F Jensen ◽  
M A Willis ◽  
M B Espinosa ◽  
A D Vitullo

Apoptosis-dependent massive germ cell death is considered a constitutive trait of the developing mammalian ovary that eliminates 65–85% of the germinal tissue depending on the species. After birth and during adult lifetime, apoptotic activity moves from the germ cell proper to the somatic compartment, decimating germ cells through follicular atresia until the oocyte reserve is exhausted. In contrast, the South American rodent Lagostomus maximus shows suppressed apoptosis-dependent follicular atresia in the adult ovary, with continuous folliculogenesis and massive polyovulation, which finally exhausts the oocyte pool. The absence of follicular atresia in adult L. maximus might arise from a failure to move apoptosis from the germinal stratum to the somatic compartment after birth or being a constitutive trait of the ovarian tissue with no massive germ cell degeneration in the developing ovary. We tested these possibilities by analysing oogenesis, expression of germ cell-specific VASA protein, apoptotic proteins BCL2 and BAX, and DNA fragmentation by TUNEL assay in the developing ovary of L. maximus. Immunolabelling for VASA revealed a massive and widespread colonisation of the ovary and proliferation of germ cells organised in nests that disappeared at late development when folliculogenesis began. No sign of germ cell attrition was found at any time point. BCL2 remained positive throughout oogenesis, whereas BAX was slightly detected in early development. TUNEL assay was conspicuously negative throughout the development. These results advocate for an unrestricted proliferation of germ cells, without apoptosis-driven elimination, as a constitutive trait of L. maximus ovary as opposed to what is normally found in the developing mammalian ovary.

Reproduction ◽  
2014 ◽  
Vol 147 (2) ◽  
pp. 199-209 ◽  
Author(s):  
P I F Inserra ◽  
N P Leopardo ◽  
M A Willis ◽  
A L Freysselinard ◽  
A D Vitullo

The female germ line in mammals is subjected to massive cell death that eliminates 60–85% of the germinal reserve by birth and continues from birth to adulthood until the exhaustion of the germinal pool. Germ cell demise occurs mainly through apoptosis by means of a biased expression in favour of pro-apoptotic members of theBCL2gene family. By contrast, the South American plains vizcacha,Lagostomus maximus, exhibits sustained expression of the anti-apoptoticBCL2gene throughout gestation and a low incidence of germ cell apoptosis. This led to the proposal that, in the absence of death mechanisms other than apoptosis, the female germ line should increase continuously from foetal life until after birth. In this study, we quantified all healthy germ cells and follicles in the ovaries ofL. maximusfrom early foetal life to day 60 after birth using unbiased stereological methods and detected apoptosis by labelling with TUNEL assay. The healthy germ cell population increased continuously from early-developing ovary reaching a 50 times higher population number by the end of gestation. TUNEL-positive germ cells were <0.5% of the germ cell number, except at mid-gestation (3.62%). Mitotic proliferation, entrance into prophase I stage and primordial follicle formation occurred as overlapping processes from early pregnancy to birth. Germ cell number remained constant in early post-natal life, but a remnant population of non-follicular VASA- and PCNA-positive germ cells still persisted at post-natal day 60.L. maximusis the first mammal so far described in which female germ line develops in the absence of constitutive massive germ cell elimination.Free Spanish abstractSpanish translation of this abstract is freely available athttp://www.reproduction-online.org/content/147/2/199/suppl/DC1


Zygote ◽  
2011 ◽  
Vol 20 (3) ◽  
pp. 219-227 ◽  
Author(s):  
C.R. Gonzalez ◽  
M.L. Muscarsel Isla ◽  
N.A. Fraunhoffer ◽  
N.P. Leopardo ◽  
A.D. Vitullo

SummaryCell proliferation and cell death are essential processes in the physiology of the developing testis that strongly influence the normal adult spermatogenesis. We analysed in this study the morphometry, the expression of the proliferation cell nuclear antigen (PCNA), cell pluripotency marker OCT-4, germ cell marker VASA and apoptosis in the developing testes of Lagostomus maximus, a rodent in which female germ line develops through abolished apoptosis and unrestricted proliferation. Morphometry revealed an increment in the size of the seminiferous cords with increasing developmental age, arising from a significant increase of PCNA-positive germ cells and a stable proportion of PCNA-positive Sertoli cells. VASA showed a widespread cytoplasmic distribution in a great proportion of proliferating gonocytes that increased significantly at late development. In the somatic compartment, Leydig cells increased at mid-development, whereas peritubular cells showed a stable rate of proliferation. In contrast to other mammals, OCT-4 positive gonocytes increased throughout development reaching 90% of germ cells in late-developing testis, associated with a conspicuous increase in circulating FSH from mid- to late-gestation. TUNEL analysis was remarkable negative, and only a few positive cells were detected in the somatic compartment. These results show that the South American plains viscacha displays a distinctive pattern of testis development characterized by a sustained proliferation of germ cells throughout development, with no signs of apoptosis cell demise, in a peculiar endocrine in utero ambiance that seems to promote the increase of spermatogonial number as a primary direct effect of FSH.


2017 ◽  
Vol 48 (3) ◽  
pp. 259-273 ◽  
Author(s):  
Pablo Ignacio Felipe Inserra ◽  
Santiago Elías Charif ◽  
Noelia Paula Di Giorgio ◽  
Lucía Saucedo ◽  
Alejandro Raúl Schmidt ◽  
...  

Author(s):  
Alejandro Raúl Schmidt ◽  
Pablo Ignacio Felipe Inserra ◽  
Santiago Andrés Cortasa ◽  
Sofía Proietto ◽  
Victoria Fidel ◽  
...  

Author(s):  
Santiago Elías Charif ◽  
Pablo Ignacio Felipe Inserra ◽  
Alejandro Raúl Schmidt ◽  
Santiago Andrés Cortasa ◽  
Sofía Proietto ◽  
...  

PLoS ONE ◽  
2019 ◽  
Vol 14 (9) ◽  
pp. e0221559 ◽  
Author(s):  
María Constanza Gariboldi ◽  
Pablo Ignacio Felipe Inserra ◽  
Sergio Lucero ◽  
Mauricio Failla ◽  
Sergio Iván Perez ◽  
...  

2012 ◽  
Vol 58 (6) ◽  
pp. 629-635 ◽  
Author(s):  
Candela Roc^|^iacute;o GONZ^|^Aacute;LEZ ◽  
Mar^|^iacute;a Laura Muscarsel ISLA ◽  
Noelia Paola LEOPARDO ◽  
Miguel Alfredo WILLIS ◽  
Ver^|^oacute;nica Berta DORFMAN ◽  
...  

Development ◽  
1998 ◽  
Vol 125 (6) ◽  
pp. 1103-1112 ◽  
Author(s):  
G.Q. Zhao ◽  
L. Liaw ◽  
B.L. Hogan

The murine Bmp8a and Bmp8b genes are tightly linked on mouse chromosome 4 and have similar expression during reproduction. Previous studies have shown that targeted mutagenesis of Bmp8b causes male infertility due to germ cell degeneration. To investigate the function of Bmp8a, we have inactivated the gene by homologous recombination. Heterozygous and homozygous Bmp8a mutants reveal normal embryonic and postnatal development. Despite high levels of Bmp8a expression in the deciduum, homozygous mutant females have normal fertility, suggesting that the gene is not essential for female reproduction. Bmp8a and Bmp8b are expressed in similar patterns in male germ cells. Unlike homozygous Bmp8btm1 mutants, homozygous Bmp8atm1 males do not show obvious germ cell defects during the initiation of spermatogenesis. However, germ cell degeneration is observed in 47% of adult homozygous Bmp8atm1 males, establishing a role of Bmp8a in the maintenance of spermatogenesis. A small proportion of the mating homozygous Bmp8atm1 males also show degeneration of the epididymal epithelium, indicating a novel role for BMPs in the control of epididymal function.


Reproduction ◽  
2006 ◽  
Vol 132 (2) ◽  
pp. 301-308 ◽  
Author(s):  
Federico Jensen ◽  
Miguel A Willis ◽  
Mirta S Albamonte ◽  
María B Espinosa ◽  
Alfredo D Vitullo

It has been widely accepted that mammalian females are born with a non-renewing, finite pool of oocytes that will be continuously cleared by atresia, with only a small proportion of them reaching ovulation. Apoptosis regulates this mass germ cell death, especially through the balance between pro- and anti-apoptotic proteins encoded by the BCL-2 gene family. The caviomorph rodent Lagostomus maximus, the South American plains viscacha, displays the highest ovulation rate known for a mammal releasing 400–800 eggs per cycle. We tested the hypothesis that in L. maximus massive polyovulation is a consequence of reduced apoptosis resulting in suppressed follicular atresia. We found that anti-apoptotic BCL-2 gene is markedly expressed in all kind of follicles from primordial to fully mature antral stages in the adult ovary of L. maximus. On the other hand, pro-apoptotic BAX gene showed weak signals or was undetectable by immunohistochemical examination. Western blot against both proteins confirmed immunohistochemical results. Screening for DNA fragmentation by TUNEL assay was conspicuously negative in ovaries from both pregnant and non-pregnant females. In addition, α-oestrogen receptor also showed an enhanced expression from primordial stage to fully mature antral follicles. Our results show that natural preferential expression of BCL-2 and restricted BAX expression greatly suppresses apoptosis in the ovary of L. maximus. This prevents the decline of the oocyte reserve by abolishing follicular atresia and enables the highest ovulation rate known for a mammal, 400–800 or more eggs per cycle.


Genome ◽  
2009 ◽  
Vol 52 (10) ◽  
pp. 891-896 ◽  
Author(s):  
Anastassia Trifonova ◽  
Peter B. Moens

Absence of spermiogenesis in mice with meiotic defects complicates the staging of meiotic arrest using light microscopy. Consequently, new methodologies are required to establish accurate relationships among germ cells. In this study, we utilized a novel approach to analyze germ cell degeneration in juvenile mice. We used terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) in combination with meiosis-specific antibodies. Germ cell degeneration is a normal component of early spermatogenesis in juvenile mice. The incidence of germ cell death was monitored at various postnatal ages of mice using the TUNEL assay to quantify the incidence of apoptosis. Cell death occurred predominantly at 15.5 days after birth. It was found that groups of apoptotic cells were apparent in tubules containing two generations of spermatocytes that form in two progressive cohorts. Electron microscopic observations further illustrated that the majority of cells in the first cohort are in late pachytene, while groups of cells in the second cohort can degenerate in early pachytene. The methodology utilized in this study is significant because it allows one to accurately determine the point at which germ cells arrest. Consequently, we believe that these methods can be applied to study animals with meiotic defects that prevent spermiogenesis.


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