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

Abstract

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, a-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.

Quantification of healthy and atretic germ cells and follicles in the developing and post-natal ovary of the South American plains vizcacha, Lagostomus maximus: evidence of continuous rise of the germinal reserve

“…This quantitative estimate based on unbiased stereological methods supports the assumption that the sustained expression of apoptosis-inhibiting BCL2 gene and the low or absent detection of apoptosis-inducing BAX gene preclude massive germ cell demise by greatly reducing apoptosis (Jensen et al 2006. Moreover, it also shows that the post-natal ovaries of L. maximus still have a proliferating germ cell population with persistence of oogonia and primordial follicle-enclosed oocytes in meiotic prophase I stage, mainly located nearest to the surface epithelium.…”

“…Massive polyovulation has been explained to occur as a consequence of the peculiar anatomy of the ovary characterised by a highly convoluted cortex that goes deeply into the medulla, substantially increasing the surface area for ovulation (Weir 1971b, Mossman & Duke 1973, Flamini et al 2009. In addition to the increased ovulation area, we observed sustained expression of apoptosis-inhibiting BCL2 gene and low expression of apoptosis-inducing BAX gene, which may be responsible for suppressing apoptosisdependent follicular atresia in the ovary of the adult female (Jensen et al 2006). Moreover, sustained BCL2 expression is a constitutive ovary-specific trait that may also play an important role in decreased apoptosis-dependent germ cell attrition throughout the foetal development period .…”

“…This needs further exploration, especially considering that this rodent displays massive ovulation, releasing up to 800 oocytes in each oestrus cycle accompanied by a considerable number of non-ovulated oocytes remaining in luteinising unruptured follicles (Weir 1971a, Jensen et al 2006. Moreover, pre-ovulatory follicles are formed during gestation, and there seems to be an ovulatory process at mid-gestation with massive formation of secondary corpora lutea (Jensen et al 2006 and reproductive life spans over 10 years (Weir 1971a). In such a dynamic ovary, de novo oogenesis may well account for the need of permanently rebuilding the tissue organisation and germ cell supply.…”

Ovarian, Hypophyseal and Hypothalamic Hormones Coordinate Mammary Gland Remodeling in Adult Lagostomus maximus: a Rodent that Shows Pseudo-Ovulation at Mid-Gestation

“…This species has attracted significant attention in the reproductive research field since female ovaries exhibit exceptional and unique characteristics among rodents. Females display natural massive poly-ovulation that can go up to 800 oocytes per cycle, the highest ovulatory rate so far recorded for a mammal, as a result of an unusual constitutive suppression of apoptosis that greatly decreases intra-ovarian oocyte dismissal caused by follicular atresia [8][9][10][11][12]. In addition, gestation lasts 154 ± 6 days [8], an unusually long period for a rodent and one of the longest recorded among hystricomorphs.…”

Estimation, morphometry and ultrastructure of ovarian preantral follicle population in agouti (Dasyprocta leporina)

“…A large amount of accessory CLs was verified in agoutis, as described for plains viscacha (Jensen et al 2006), paca (Reis et al 2006), and chinchillas (Sánchez-Toranzo et al 2014). Such structures were previously identified by Weir (1971) that distinguished accessory from functional CLs by the smaller size and presence of a degenerating oocyte or remnants of the zona pellucida.…”