Naturally suppressed apoptosis prevents follicular atresia and oocyte reserve decline in the adult ovary of Lagostomus maximus (Rodentia, Caviomorpha)

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.

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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 ◽

10.1530/rep-10-0463 ◽

2011 ◽

Vol 141 (5) ◽

pp. 633-641 ◽

Cited By ~ 26

Author(s):

N P Leopardo ◽

F Jensen ◽

M A Willis ◽

M B Espinosa ◽

A D Vitullo

Keyword(s):

Germ Cell ◽

Germ Cells ◽

Ovarian Tissue ◽

Tunel Assay ◽

South American ◽

Follicular Atresia ◽

The South ◽

Cell Degeneration ◽

Lagostomus Maximus ◽

Apoptotic Activity

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.

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ERα and GnRH co-localize in the hypothalamic neurons of the South American plains vizcacha, Lagostomus maximus (Rodentia, Caviomorpha)

Journal of Molecular Histology ◽

10.1007/s10735-017-9715-6 ◽

2017 ◽

Vol 48 (3) ◽

pp. 259-273 ◽

Cited By ~ 9

Author(s):

Pablo Ignacio Felipe Inserra ◽

Santiago Elías Charif ◽

Noelia Paula Di Giorgio ◽

Lucía Saucedo ◽

Alejandro Raúl Schmidt ◽

...

Keyword(s):

South American ◽

The South ◽

Hypothalamic Neurons ◽

Lagostomus Maximus

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Involvement of hyaluronan synthesis in ovarian follicle growth in rats

Reproduction ◽

10.1530/rep-13-0464 ◽

2014 ◽

Vol 147 (2) ◽

pp. 189-197 ◽

Cited By ~ 11

Author(s):

Noriyuki Takahashi ◽

Wataru Tarumi ◽

Bunpei Ishizuka

Keyword(s):

Ovarian Follicle ◽

Primary Site ◽

Corpora Lutea ◽

Follicular Atresia ◽

Follicle Growth ◽

Adult Rats ◽

Antral Follicles ◽

Cell Layers ◽

Ha Synthase

Most of the previous studies on ovarian hyaluronan (HA) have focused on mature antral follicles or corpora lutea, but scarcely on small preantral follicles. Moreover, the origin of follicular HA is unknown. To clarify the localization of HA and its synthases in small growing follicles, involvement of HA in follicle growth, and gonadotropin regulation of HA synthase (Has) gene expression, in this study, perinatal, immature, and adult ovaries of Wistar-Imamichi rats were examined histologically and biochemically and byin vitrofollicle culture. HA was detected in the extracellular matrix of granulosa and theca cell layers of primary follicles and more advanced follicles. Ovarian HA accumulation ontogenetically started in the sex cords of perinatal rats, and its primary site shifted to the intrafollicular region of primary follicles within 5 days of birth. TheHas1–3mRNAs were expressed in the ovaries of perinatal, prepubertal, and adult rats, and the expression levels ofHas1andHas2genes were modulated during the estrous cycle in adult rats and following administration of exogenous gonadotropins in immature acyclic rats. TheHas1andHas2mRNAs were predominantly localized in the theca and granulosa cell layers of growing follicles respectively. Treatments with chemicals known to reduce ovarian HA synthesis induced follicular atresia. More directly, the addition ofStreptomyceshyaluronidase, which specifically degrades HA, induced the arrest of follicle growth in anin vitroculture system. These results indicate that gonadotropin-regulated HA synthesis is involved in normal follicle growth.

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Distribution of kisspeptin system and its relation with gonadotropin-releasing hormone in the hypothalamus of the South American plains vizcacha, Lagostomus maximus

General and Comparative Endocrinology ◽

10.1016/j.ygcen.2021.113974 ◽

2021 ◽

pp. 113974

Author(s):

Alejandro Raúl Schmidt ◽

Pablo Ignacio Felipe Inserra ◽

Santiago Andrés Cortasa ◽

Sofía Proietto ◽

Victoria Fidel ◽

...

Keyword(s):

Gonadotropin Releasing Hormone ◽

South American ◽

The South ◽

Releasing Hormone ◽

Lagostomus Maximus

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Melatonin is involved in the modulation of the hypothalamic and pituitary activity in the South American plains vizcacha, Lagostomus maximus

Journal of Comparative Physiology B ◽

10.1007/s00360-021-01405-6 ◽

2021 ◽

Author(s):

Santiago Elías Charif ◽

Pablo Ignacio Felipe Inserra ◽

Alejandro Raúl Schmidt ◽

Santiago Andrés Cortasa ◽

Sofía Proietto ◽

...

Keyword(s):

South American ◽

The South ◽

Lagostomus Maximus

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Unexpected low genetic variation in the South American hystricognath rodent Lagostomus maximus (Rodentia: Chinchillidae)

PLoS ONE ◽

10.1371/journal.pone.0221559 ◽

2019 ◽

Vol 14 (9) ◽

pp. e0221559 ◽

Cited By ~ 1

Author(s):

María Constanza Gariboldi ◽

Pablo Ignacio Felipe Inserra ◽

Sergio Lucero ◽

Mauricio Failla ◽

Sergio Iván Perez ◽

...

Keyword(s):

Genetic Variation ◽

South American ◽

The South ◽

Lagostomus Maximus

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Differential expression of CART in ewes with differing ovulation rates

Reproduction ◽

10.1530/rep-16-0657 ◽

2017 ◽

Vol 153 (4) ◽

pp. 471-479 ◽

Cited By ~ 6

Author(s):

Jennifer L Juengel ◽

Michelle C French ◽

Laurel D Quirke ◽

Alexia Kauff ◽

George W Smith ◽

...

Keyword(s):

Differential Expression ◽

Expression Pattern ◽

Follicular Fluid ◽

Follicular Phase ◽

Distinct Pattern ◽

Ovulation Rate ◽

Differentially Expressed ◽

Antral Follicles ◽

Cart Peptide

We hypothesised that cocaine- and amphetamine-regulated transcript (CARTPT) would be differentially expressed in ewes with differing ovulation rates. Expression of mRNA forCARTPT, as well asLHCGR,FSHR,CYP19A1andCYP17A1was determined in antral follicles ≥1 mm in diameter collected during the follicular phase in ewes heterozygous for the Booroola and Inverdale genes (I+B+; average ovulation rate 4) and ++ contemporaries (++; average ovulation rate 1.8). In ++ ewes (n = 6),CARTPTwas expressed in small follicles (1 to <3 mm diameter), where 18.8 ± 2.5% follicles expressedCARTPT. CART peptide was also detected in follicular fluid of some follicles of ++ ewes. In I+B+ ewes, 5/6 ewes did not have any follicles that expressedCARTPT, and no CART peptide was detected in any follicle examined. Expression pattern ofCYP19A1differed between I+B+ and ++ ewes with an increased percentage of small and medium follicles (3 to <4.5 mm diameter) but decreased percentage of large follicles (≥4.5 mm diameter) expressingCYP19A1in the I+B+ ewes. Many of the large follicles from the I+B+ ewes appeared non-functional and expression ofLHCGR,FSHR,CYP17A1andCYP19A1was less than that observed in ++ ewes. Expression ofFSHRandCYP17A1was not different between groups in small and medium follicles, butLHCGRexpression was approximately double in I+B+ ewes compared to that in ++ ewes. Thus, ewes with high ovulation rates had a distinct pattern of expression ofCARTPTmRNA and protein compared to ewes with normal ovulation rates, providing evidence for CART being important in the regulation of ovulation rate.

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Initial ovulation rate and follicle population after injection of inhibin-neutralizing antiserum in the late-prepubertal rat

Journal of Endocrinology ◽

10.1677/joe.0.1300289 ◽

1991 ◽

Vol 130 (2) ◽

pp. 289-296 ◽

Cited By ~ 1

Author(s):

H. J. Sander ◽

H. M. A. Meijs-Roelofs ◽

E. C. M. van Leeuwen ◽

P. Kramer ◽

W. A. van Cappellen

Keyword(s):

Neutralizing Antibodies ◽

Ovulation Rate ◽

Female Rats ◽

Corpora Lutea ◽

Female Rat ◽

Follicle Growth ◽

Immune Control ◽

Immature Female ◽

Antral Follicles ◽

Control Serum

ABSTRACT In late-prepubertal female rats passive immunoneutralization of endogenous inhibin was achieved by injection of inhibin antiserum. Effects on follicle population, timing of sexual maturation, ovulation rate at first and second oestrus and serum FSH levels were studied. Rats were injected with antiserum, (non-immune) control serum from castrated sheep (castrated serum) or their IgG fractions, or with saline on day 33 or 3 or 2 days (days −3/−2) before the expected day of first ovulation, day 38·5±0·2 (n = 70). Blood was collected from different subgroups at 8, 24 and 48 h, and at first and second oestrus after injection. At necropsy, ovaries were histologically prepared for differential counting of follicles (48 h and first oestrus) and counting of corpora lutea (CL; first and second oestrus) as an index of ovulation rate. Results from rats injected with either serum or its IgG fraction were not different, as was the case when rats were injected with either castrated serum or saline. Thus, results from groups treated with antiserum and antiserum IgG were combined and labelled 'antiserum', and the castrated serum, castrated serum IgG and saline-treated groups were combined and labelled 'control'. The activity of inhibin-neutralizing antibodies in the circulation of antiserum-treated rats was reduced by 43% between 8 h and second oestrus after injection, as determined by the binding of purified bioactive radioiodinated 31 kDa bovine inhibin. After antiserum injection on day 33, more healthy antral follicles (vol. > 100 × 105 μm3, diameter > 260 μm) were present in the ovaries at 48 h (70·6 vs 54·4; P < 0·05) and at first oestrus (73·1 vs 50·8; P < 0·05) if first oestrus was reached within 5 days, but numbers were not different if first oestrus was more than 5 days after injection (52·6 vs 50·8). The number of CL after injection of antiserum on day 33 was increased at first oestrus compared with control (13·4±0·5, n = 30, vs 10·0±0·2, n = 40; P<0·001), an effect that was even more clearly present in antiserum-injected rats ovulating within 5 days (14·4±0·7, n = 20; P < 0·001). Rats injected with antiserum at days −3/−2 showed a doubling of ovulation rate at first oestrus when compared with control animals (21·5±0·8, n = 12, vs 10·5±0·2, n = 15; P < 0·001). No differences in the number of CL was seen at second oestrus. Age and body weight on the day of first ovulation were not influenced by antiserum treatment. Serum FSH was significantly (P < 0·01) increased at 8 h after antiserum injection on either day 33 or on days −3/−2 to a level of 250 and 800% of control levels respectively. Thus, injection with inhibin–neutralizing antiserum into prepubertal female rats resulted, through an increase in serum FSH concentration 8 h after injection, in the growth of additional numbers of healthy antral follicles. Supranormal ovulation rate occurred if antiserum injections were given within the last 5 days before first ovulation, with a maximal ovulation rate after injection on days −3/−2. The data support the view that, in the immature female rat during the last 5 days before the day of first ovulation, inhibin is (through its regulation of serum FSH levels) progressively involved in the control of follicle growth and ovulation rate. Journal of Endocrinology (1991) 130, 289–296

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The effects of inbreeding on the components of litter size in mice

Genetics Research ◽

10.1017/s0016672300010776 ◽

1967 ◽

Vol 10 (1) ◽

pp. 73-80 ◽

Cited By ~ 23

Author(s):

J. C. McCarthy

Keyword(s):

Litter Size ◽

Inbreeding Depression ◽

First Generation ◽

Inbreeding Coefficient ◽

Ovulation Rate ◽

Corpora Lutea ◽

Base Population ◽

Pregnant Females ◽

Sib Mating ◽

Size At Birth

Twenty-four lines were bred from a base population of outbred Q mice by continued full-sib mating. Inbreeding depression in litter size at birth was observed. This decline in litter size was analysed in terms of ovulation rate, the incidence of preimplantation mortality and the incidence of postimplantation mortality. Pregnant females were dissected at 17½ days' gestation and the numbers of corpora lutea, or eggs, and of live and dead embryos were counted. Matings were arranged so that separate estimates of the effects of inbreeding in the mother and in the litter on the components of litter size could be obtained.In the first generation of inbreeding when the inbreeding coefficient of the litter was raised from 0 to 25% decline in litter size was attributable to an increased incidence of preimplantation mortality.In the second and fourth generations decline in litter size was attributable to (1) a reduction in the number of eggs ovulated by the inbred mothers, (2) an increased incidence of preimplantation mortality which resulted from inbreeding in the mother. No evidence of significant effects on mortality of inbreeding in the litter was obtained in the later generation of inbreeding.These findings are discussed in the context of previous work on the effects of inbreeding and crossing on litter size and its components in mice and pigs.

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