Alterations in gonadotropin, apoptotic and metabolic pathways in granulosa cells warrant superior fertility of the Dummerstorf high fertility mouse line 1

Abstract

The development and maturation of ovarian follicles is a complex and highly regulated process, which is essential for successful ovulation. During recent decades, several mouse models provided insights into the regulation of folliculogenesis. In contrast to the commonly used transgenic or knockout mouse models, the Dummerstorf high-fertility mouse line 1 (FL1) is a worldwide unique selection experiment for increased female reproductive performance and extraordinary high fertility. Interactions of cycle-related alterations of parameters of the hypothalamic pituitary gonadal axis and molecular factors in the ovary lead to improved follicular development and therefore increased ovulation rates in FL1 mice. FL1 females almost doubled the number of ovulated oocytes compared to the unselected control mouse line. To gain insights into the cellular mechanisms leading to the high fertility phenotype we used granulosa cells isolated from antral follicles for mRNA sequencing. Based on the results of the transcriptome analysis we additionally measured hormones and growth factors associated with follicular development to complement the picture of how the signaling pathways are regulated. While IGF1 levels are decreased in FL1 mice in estrus, we found no differences in insulin, prolactin and oxytocin levels in FL1 mice compared to the control line. The results of the mRNA sequencing approach revealed that the actions of insulin, prolactin and oxytocin are restricted local to the granulosa cells, since hormonal receptor expression is differentially regulated in FL1 mice. Additionally, numerous genes, which are involved in important gonadotropin, apoptotic and metabolic signaling pathways in granulosa cells, are differentially regulated in granulosa cells of FL1 mice.We showed that an overlap of different signaling pathways reflects the crosstalk between gonadotropin and growth factor signaling pathways, follicular atresia in FL1 mice is decreased due to improved granulosa cell survival and by improving the efficiency of intracellular signaling, glucose metabolism and signal transduction, FL1 mice have several advantages in reproductive performance and therefore increased the ovulation rate. Therefore, this worldwide unique high fertility model can provide new insights into different factors leading to improved follicular development and has the potential to improve our understanding of high fertility.

Key mRNAs and lncRNAs of pituitary that affect the reproduction of FecB + + small tail han sheep

“…This process was achieved by competitively inhibiting the combination of IGF and IGFR (Insulin Like Growth Factor 1 Receptor) [ 49 ]. The IGF system has been widely documented to affect animal reproduction [ 50 , 51 ]. In vitro experiments at the pituitary level showed that exogenous IGF-1 can increase the secretion of LH in sheep pituitary cells [ 52 ].…”

Identification of microRNAs implicated in modulating resveratrol-induced apoptosis in porcine granulosa cells

“…Apoptosis of granulosa cells is closely associated with follicular atresia ( Wang et al, 2023 ), process controlled by reproductive hormones and cytokines ( Santos et al, 2022 ; Bevilaqua et al, 2023 ; Grynberg et al, 2023 ; Li et al, 2023 ). Numerous studies performed in chicken, rodents and pigs have shown that proapoptotic and antiapoptotic factors contribute to follicular atresia triggering the apoptosis of granulosa cells ( Guo et al, 2019 ; Han et al, 2023 ; Ludwig et al, 2023 ). In the current study, we aimed, with the use of sRNA sequencing, to examine the effect of natural polyphenol RSV on apoptosis of porcine granulosa cells.…”

The role of serum-glucocorticoid regulated kinase 1 in reproductive viability: implications from prenatal programming and senescence

“…The expression of SGK1 is present in oocytes of primordial follicles, and is very low or even undetected in granulosa cells of preantral follicles where the cells are proliferating at an extremely slow rate [ 37 ]. As the granulosa cells differentiate to nondividing luteal cells, SGK1 in immature granulosa cells is induced rapidly by FSH and more specifically LH, physiological stimulators of granulosa cell proliferation and differentiation [ 35 , 38 ]. Mediated by Sp1 binding region in the promotor of SGK1 gene, this marked increase of SGK1 expressions by FSH through the cAMP/PKA pathway is followed by a transient decline, and then reaches the maximal level as cells differentiate, coinciding temporally with the secondary burst of proliferative activity that occurs in granulosa cells of large preantral follicles as they come into preovulatory follicles [ 38 , 39 ].…”

“…During follicular development, the induction of SGK1 is closely related to the specific stage of granulosa cell proliferation [ 36 ]. BMP15 and GDF9 promote FSH-induced progesterone synthesis in preovulatory follicular granulosa cells [ 72 ], and significantly increase the expression of SGK1 under the mediation of Sp1 [ 38 , 73 ]. Thus, BMP2, BMP7, BMP15 and GDF9 play a role in the regulation of SGK1.…”