Sequential Effects of Follicle-Stimulating Hormone and Luteinizing Hormone on Mouse Cumulus Expansion in Vitro1

Abstract

LH and FSH play critical roles in the development and function of the cumulus oophorus of the mammalian follicle, but the significance of cumulus LH receptors and the nature of the functional interaction between LH and FSH in relation to the process of cumulus expansion are not well understood. Controversy may arise from contradictory results of cumulus LH receptor assays, possibly as a consequence of relative sensitivities of the assays utilized, limited availability of tissue of specific developmental stages, or limitations on the access of radiolabeled ligands to cumulus LH receptors in the intact follicle. It has also been difficult to understand the basis for the apparent difference in gonadotropin requirements for cumulus expansion in vitro and in vivo; FSH seems to be required for expansion in vitro and LH initiates expansion in vivo. In this study, we show that expansion of mouse cumulus-oocyte complexes (COCs) in vitro occurs to a degree comparable to that seen in vivo when COCs are challenged with highly purified FSH (hpFSH) and highly purified LH (hpLH) together or when treatment with hpFSH precedes treatment with LH. Saturation radioreceptor assays revealed that FSH up-regulates cumulus cell LH receptors in the absence of LH and that LH may stimulate expansion upon binding to these acutely formed receptors. A model of cumulus expansion describing effects of both FSH and LH in vivo is proposed.

In vitro maturation of cumulus–partially enclosed immature human oocytes by priming with gonadotropin

“…However, in the later GV stage, FSH up-regulates LH receptors, resulting in germinal vesicle breakdown (GVBD) and meiotic resumption by LH action on the surrounding CC (15,16). All previous investigations support the findings of this study; specifically, LH stimulation, not FSH, contributes to the nuclear maturation of human GV-stage oocytes (17)(18)(19)(20)(21)(22)(23)(24).…”

LH/hCGR gene expression in human cumulus cells is linked to the expression of the extracellular matrix modifying gene TNFAIP6 and to serum estradiol levels on day of hCG administration

“…However, as FSH is known to stimulate LH/hCGR expression (Shi and Segaloff, 1995), the difference observed in LH/hCGR gene expression between the three groups could be reflected by differences in FSH responsiveness. Moreover, saturation ratio receptor assays revealed that FSH up-regulates CC LH/hCGR receptors in the absence of LH, and subsequently LH stimulates COC expansion and oocyte maturation upon binding to these newly formed receptors (Chen et al, 1994;Kawashima et al, 2008). However, in the present study, there was no difference in the total FSH stimulation dose between the three LH/hCGR groups (low, medium, high), suggesting that the difference in FSH responsiveness is not associated with the modulation of LH/hCGR gene expression.…”

Derivation of Histocompatible Stem Cells from Ovarian Tissue

“…Serum contains bioactive materials that promote cell adhesion and proliferation [51]. In an in vitro environment, follicle-stimulating hormone is essential for the growth and development of preantral follicles, stimulating proliferation and differentiation of the granulosa cells surrounding the oocyte [55][56][57], and luteinizing hormone is required to initiate growth of preantral follicles and to stimulate antrum formation in the follicles [55,58,59] The follicle retrieved by enzymatic method: the basement membrane was not visible, and the theca cells were completely detached from the membrane. Scale bars=50 μm (reprinted with permission of Lee ST et al, Zygotes, 2007; 15: 109-116).…”

“…Serum contains bioactive materials that promote cell adhesion and proliferation [51]. In an in vitro environment, follicle-stimulating hormone is essential for the growth and development of preantral follicles, stimulating proliferation and differentiation of the granulosa cells surrounding the oocyte [55][56][57], and luteinizing hormone is required to initiate growth of preantral follicles and to stimulate antrum formation in the follicles [55,58,59]. The growth factors used in culture include EGF [60], activin A [55], basic fibroblast growth factor [60,61], insulin-like growth factor-1 [60,62], growth differentiation factor 9 [63] and leukemia inhibitory factor [54,64].…”