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

Abstract

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

Early embryonic development and spatiotemporal localization of mammalian primordial germ cell-associated proteins in the basal rodent Lagostomus maximus

“…During migration, SOX17 is down-regulated, and its expression is restored in oogonia after the colonization of the genital ridges. It seems reasonable to consider that SOX17 could act as a regulator of proliferation and the cell cycle 28 , contributing to the continuous rise of healthy germ cells, which characterizes the ovaries of L. maximus throughout fetal life, in the presence of a minimal rate of apoptosis-driven, germ cell attrition 29 .…”

When stem cells grow old: phenotypes and mechanisms of stem cell aging

“…Whether or not females possess germline stem cells is an area of active debate. While males remain fertile throughout life, female oogenesis from oogonia in the developing ovary ceases before birth, although some mammals, including several species of bats, bushbabies and a species of chinchilla, are reported to continue oogenesis postnatally (Antonio-Rubio et al, 2013;Butler and Juma, 1970;Inserra et al, 2013). Some researchers have proposed that these species (and ostensibly all mammals) possess stem cells that can generate oocytes, called oogonial stem cells (OSCs).…”

Local production of neurostradiol affects gonadotropin-releasing hormone (GnRH) secretion at mid-gestation inLagostomus maximus(Rodentia, Caviomorpha)

“…Handling and euthanasia of animals were performed in accordance with the NIH guidelines for the care and use of laboratory animals (NIH 1985, CCAC 2002, and CCAC 2003. In order to obtain females at different reproductive stages, captures were planned according to the natural reproductive cycle, previously described by Llanos and Crespo (1952), and on our own previous expertise in the field (Jensen et al 2006(Jensen et al , 2008Dorfman et al 2011Dorfman et al , 2013Leopardo et al 2011;Halperin et al 2013;Inserra et al 2014Inserra et al , 2017Charif et al 2016). Pregnant vizcachas were captured during the breeding season that lasts from April to August.…”

“…In contrast to most mammals, female vizcacha shows massive polyovulation of up to 800 oocytes per estrous cycle, the highest ovulatory rate so far recorded for a mammal (Weir 1971a,b;Jensen et al 2006). Massive ovulation results from an unusual constitutive suppression of apoptosis that precludes intraovarian oocyte dismissal through follicular atresia (Jensen et al 2006(Jensen et al , 2008Leopardo et al 2011;Inserra et al 2014).…”