The Ovary of the Gestating South American Plains Vizcacha (Lagostomus maximus): Suppressed Apoptosis and Corpora Lutea Persistence1

Abstract

The South American plains vizcacha, Lagostomus maximus, displays an exceptional ovulation rate of up to 800 eggs per cycle, the highest rate recorded for a mammal. Massive polyovulation arises from the overexpression of the apoptosis-inhibiting BCL2 gene leading to a suppression of apoptotic pathways responsible for follicular atresia in mammals. We analyzed the ovarian histology, ovarian apoptosis, and apoptosis-related protein expression with special emphasis in corpora lutea throughout the 5-mo-long gestation period, at parturition day and early postpartum, in L. maximus. Corpora lutea were abundant throughout gestation with no sign of structural regression even at the end of gestation. Both immunohistochemistry and Western blot analysis showed strong signals for apoptosis-inhibiting BCL2 protein, whereas the proapoptotic BAX protein was just detected in isolated luteal cells in gestating females and postpartum females. Apoptosis-associated DNA fragmentation detected by TUNEL was very scarce and occasional and correlated with BAX detection in luteal cells. Marked expression of progesterone and alpha-estrogen receptors in luteal cells was found at early, mid-, and late gestation as well as at parturition day and early postpartum samples. Additionally, serum level of progesterone increased markedly to reach maximal values at late gestation and decreasing at parturition to levels found at early gestation, suggesting that corpora lutea remained functional throughout gestation. These results point out that the unusual ovarian environment of L. maximus in which germ cell demise is abolished through antiapoptotic BCL2 gene overexpression also preserves structural integrity and functionality of corpora lutea during the whole gestation. Overexpression of antiapoptotic BCL2 gene may represent a strategy for an essential need of ovary and corpora lutea in order to maintain pregnancy until term.

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.…”

“…In addition, gestation lasts 154 ± 6 days [8], an unusually long period for a rodent and one of the longest recorded among hystricomorphs. Moreover, pregnant females exhibit an ovulatory event at mid-pregnancy that leads to a considerable number of secondary corpora lutea with oocyte retention (i.e., pseudo-ovulation) and to an important rise of the progesterone levels [10,11,13]. This boost up in the circulating progesterone may contribute to an accurate maintenance of the uterus and embryo development up to the end of pregnancy [11,14].…”

“…Moreover, pregnant females exhibit an ovulatory event at mid-pregnancy that leads to a considerable number of secondary corpora lutea with oocyte retention (i.e., pseudo-ovulation) and to an important rise of the progesterone levels [10,11,13]. This boost up in the circulating progesterone may contribute to an accurate maintenance of the uterus and embryo development up to the end of pregnancy [11,14]. Given that ovarian hormones modulate growth and development of post-pubertal mammary glands, the reproductive peculiarities of the ovaries of L. maximus make of this species an interesting model to examine the mammary glands morphology according to its reproductive status.…”

Histological characterization of gonadotropin-releasing hormone (GnRH) in the hypothalamus of the South American plains vizcacha (Lagostomus maximus)

“…The massive ovulation in L. maximus arises from a strong suppression of apoptosis-dependent follicular atresia that is driven through an over-expression of the anti-apoptotic BCL2 gene and a basal or absent expression of pro-apoptotic BAX gene both in the developing and adult ovary (Jensen et al 2006;Leopardo et al 2011). This pattern of gene expression supports a continuous oogenesis and folliculogenesis in the mature ovary that seems to execute constitutive massive germ cell elimination characterizing the mammalian ovary through polyovulation (Jensen et al 2006(Jensen et al , 2008.…”

“…Age was determined through the body size and weight, and dry crystalline lens weight according to Jackson (1986). All animals showed comparable values of serum estradiol (27.2 ± 1.8 pg/ml) and progesterone (1.09 ± 0.21 pg/ml), determined according to Jensen et al (2008).…”