The role of combining medroxyprogesterone 17-acetate with human menopausal gonadotropin in mouse ovarian follicular development

Abstract

Medroxyprogesterone 17-acetate (MPA) combined with human menopausal gonadotropin (hMG) has been effectively used for ovarian stimulation in clinical practice. However, the molecular mechanism of MPA + hMG treatment in follicular development is poorly described. Here we performed a study to investigate the impact of MPA + hMG on ovarian stimulation utilizing a mouse model in vivo. Forty female BALB/C mice were randomly divided into four groups of 10 each and treated during ciestrus stage and continued for 5 days: control group, MPA group, hMG group, and MPA + hMG group. Morphological and molecular biology methods were used for detecting serum hormones and ovarian function. MPA + hMG group exhibited increasing follicle stimulating hormone (FSH), antral follicle, FSH receptor (FSHR) and phosphorylated mammal target of rapamycin (p-mTOR), and decreasing luteinizing hormone (LH), estradiol (E2), progesterone (P), corpus luteum, phosphoinositide 3-kinase (PI3K), Akt and mTOR compared with control group. In contrast, MPA + hMG group showed reduced FSH, LH, E2, P, corpus luteum, LH receptor (LHR), and activated PI3K,/Akt/mTOR pathway compared with hMG group (P < 0.05). Collectively, these data definitively established that MPA plus hMG may modulate the hormone, hormone receptor and PI3K/Akt/mTOR signaling pathway to influence follicular development in the mouse ovary. Our study provides overwhelming support for MPA + hMG as an effective treatment for infertility in women.

Interplay Between mTOR and Hippo Signaling in the Ovary: Clinical Choice Guidance Between Different Gonadotropin Preparations for Better IVF

“…Cytoskeleton remodeling is one of the key factors regulating Hippo signaling and promoting the nuclear localization of YAP/TAZ complex ( 86 ). Importantly, recent findings in mouse models show that hMG administration leads to activation of the mTOR pathway ( 87 ), and GnRH induces cytoskeleton reorganization (a key process for the synthesis and secretion of gonadotropins) by activation of the mTOR kinase ( 88 ). Actin cytoskeleton dynamics mediates vital roles, also, for oocyte meiotic cell divisions through Hippo and mTOR signaling ( 89 – 91 ).…”

The Effects of Zearalenone on the Localization and Expression of Reproductive Hormones in the Ovaries of Weaned Gilts

“…It has been reported that FSH, together with other paracrine factors, regulates the development of the primary follicles toward the preantral and antral stages, and a large number of LHR appear under the FSH stimulation [ 20 ]. Previous research has studied the localizations or expressions of GnRHR, FSHR and LHR in the ovaries of rats, ewes and rabbits [ 21 , 22 , 23 , 24 , 25 ]. More and more evidence showed that E 2 and ZEA induced precocious puberty in female rats by increasing the concentrations of serum FSH, LH and GnRH [ 26 , 27 , 28 ].…”

Chaiyu-Dixian Formula Exerts Protective Effects on Ovarian Follicular Abnormal Development in Chronic Unpredictable Mild Stress (CUMS) Rat Model

“…Therefore, maintaining the growth and development of follicles plays an important role in women's reproduction. This process is not only affected by different hormones and growth factors through endocrine, autocrine, and paracrine patterns, but also regulated by a variety of signaling pathways (Wu et al, 2012b;Fernandois et al, 2016;Hayes et al, 2016;Wen et al, 2018). The brainderived neurotrophic factor (BDNF) is one of these factors.…”