Endometrial Receptivity Markers in Mice Stimulated With Raloxifene Versus Clomiphene Citrate and Natural Cycles

Abstract

Ovulation induction therapy with clomiphene citrate can suppress endometrial receptivity. Raloxifene may be an alternative therapeutic for women with ovulatory disorders. This study aimed to compare the expression of endometrial receptivity markers, including homeobox gene 10 (HOXA10), integrin β3, and leukemia inhibitory factor (LIF), as well as pinopode production during the implantation window in mice stimulated with raloxifene and clomiphene citrate and natural cycles. Thirty-six 8-week-old female Kunming mice were randomly divided into 3 groups (n = 12) and administered daily raloxifene (22 mg/kg), clomiphene citrate (18 mg/kg), and normal saline (1 mL), respectively, by gavage. Two days later, mice were injected with 5 IU human chorionic gonadotropin and mated. Successfully mated female animals were identified with vaginal plugs designated gestation day 1. At day 4.5, pregnant donor mice were euthanized, and uterus samples were collected for immunohistochemistry, quantitative polymerase chain reaction, Western blot, and scanning electron microscopy analyses. Homeobox gene 10, integrin β3, and LIF messenger RNA (mRNA) and protein levels were significantly higher in the raloxifene-treated animals compared with the clomiphene citrate group (all P < .05) but not significantly different from saline group values, except for LIF and integrin β3 mRNA levels (P < .05). Pinopodes were abundant and well developed in the raloxifene and saline groups; however, in the clomiphene citrate-treated mice, fewer and poorly developed pinopodes were obtained. In mice, raloxifene had no effect on HOXA10, integrin β3, and LIF expression as well as pinopode production, suggesting it has no adverse effects on endometrial receptivity. Raloxifene may provide a viable alternative oral ovulation induction agent to clomiphene citrate.

miR‐26a promoted endometrial epithelium cells (EECs) proliferation and induced stromal cells (ESCs) apoptosis via the PTEN‐PI3K/AKT pathway in dairy goats

“…The effect of miR‐26a on the surface morphology of EECs were detected by SEM (Chen et al, ). In short, glutaraldehyde‐fixed (2.5%) cell samples were thoroughly washed with PBS buffer, dehydrated in a graded ethanol series, placed in 2% isoamyl alcohol for 3 hr, and received critical point drying.…”

Comparison of pregnancy outcomes following fresh and electively frozen single blastocyst transfer in natural cycle and clomiphene-stimulated IVF cycles

“…Reduced endometrial thickness is caused by CC-induced inhibition of epithelial cell proliferation and oestrogen response element transactivation in the endometrium (Amita et al , 2010). Furthermore, ovarian stimulation using CC adversely affects uterine receptivity by reducing the endometrial expression of Homeobox gene 10, integrin αvβ3 and leukaemia inhibitory factor during the implantation period (Bao et al , 2009; Chen et al , 2016). A recent systematic review (Gadalla et al , 2018) reported the adverse effects of CC administration on the endometrium, which resulted in lower pregnancy and LBR.…”

In search for an ideal marker of endometrial receptivity: from histology to comprehensive molecular genetics-based approaches

“…Объем регрессирующих пиноподий (поздняя лютеиновая фаза) начинает снижаться, на поверхности появляются складки из цитоплазматической мембраны и вновь становятся заметными микроворсинки [17,54,55]. Различают несколько степеней относительного количества пиноподий в зависимости от доли трансформированных секреторных клеток в образце: «0» -полное отсутствие; «1» -незначительное количество (пиноподии покрывают менее 25% площади поверхности); «2» -умеренное количество (пиноподии занимают 25-50% площади поверхности); «3» -множество (более 50% площади поверхности образца занято пиноподиями) [56].…”