Involvement of GDF-9, leptin, and IGF1 receptors associated with adipose tissue transplantation on fertility restoration in obese anovulatory mice

Abstract

The aim was to analyze the effect of adipose tissue transplantation on growth differentiation factor-9 (GDF-9), insulin growth factor 1 receptor (IGF1R), and leptin receptor (LEPR) protein expression in ovaries of obese anovulatory mice. Leptin-deficient female (ob/ob) and wild-type mice were divided into untreated ob/ob mice and gonadal white adipose tissue transplanted ob/ob mice, with evaluation after 7, 15, and 45 days and compared to control wild-type mice. The corporal weight and glycemia levels increased in the obese group concomitant with polymicrocyst formation and abundant estrone, mimicking anovulatory disease. In the treated group after 45 days, glycemia, weight, ovarian size, and number of follicles were decreased and corpora lutea were decreased. The analysis of GDF-9 revealed that, whereas control ovaries presented follicular localization, the obese ovary lacked this protein. On the other hand, obese ovaries showed elevated expression of IGF1R that was normalized after the transplantation. Finally, LEPR was reduced in obese ovaries, and adipose tissue transplantation was efficient in returning it to normal levels. In conclusion, the adipose tissue transplantation, especially after 45 days, seems to stimulate ovulation, supported by the fact that several proteins involved in ovulation returned to basal levels.

Expression of adipokine and lipid metabolism genes in adipose tissue of dairy cows differing in a female fertility quantitative trait locus

“…Sebastien Elis ,* † ‡ § 1 Stephanie Coyral-Castel ,* † ‡ § Sandrine Freret ,* † ‡ § Juliette Cognié ,* † ‡ § Alice Desmarchais ,* † ‡ § Alice Fatet ,* † ‡ § Christelle Rame ,* † ‡ § Eric Briant ,* † ‡ § Virginie Maillard ,* † ‡ § and Joëlle Dupont * † ‡ § Ali, 2010), as well as to exert some well-known effects on reproductive functions (Campos et al, 2008;Briana and Malamitsi-Puchner, 2010;Tersigni et al, 2011;Dupont et al, 2012). Moreover, some publications suggest a role of adipose tissue secretion in sustaining proper fertility; indeed, fat transplantation in leptin knockout mice restores fertility in these animals (Klebanov et al, 2005;Pereira et al, 2011). Leptin is suggested to be a link between energy balance and reproductive function (Diskin et al, 2003).…”

Molecular pathways involved in the improvement of non-alcoholic fatty liver disease

“…In Lep ob/ob mice, short-term leptin treatment may not correct hepatocyte dysfunction and steatosis (Leclercq et al 2006). Although WAT transplantation was effective for the treatment and prevention of obesity, as well as of endocrine/metabolic alterations associated with leptin deficiency, it exerted profound effects on multiple physiological functions in Lep ob/ob mice: reduced body weight gain and IR and restored fertility (Klebanov et al 2005, Sennello et al 2006, Barros et al 2009, Pereira et al 2011. However, the assessment of NAFLD progression after WAT transplantation has not been evaluated yet.…”

Leptin Causes the Early Inhibition of Glycolysis- and TCA Cycle-Related Genes in the Brain of Ob/Ob Mice to Restore Fertility

“…It is largely known that leptin plays a primary role in regulating homeostasis, obesity and fertility [23] [28]. Moreover, in a previous work, Pereira et al (2009) clearly demonstrated that WAT transplantation decreases insulin resistance and restores fertility in female ob/ob mice [9]. Behind these physiological and morphological changes lay complex molecular interactions that deserve to be better understood.…”

“…These animals were maintained in a temperature-controlled environment at approximately 24˚C under a 12/12-h light-dark cycle and were handled at least once a week. Five ob/ob mice received a white adipose tissue (WAT) transplant as described by Gavrilova and Marcus-Samuels et al (2000) [29] and Pereira et al (2011) [9]: the adipose gonad tissue samples that were obtained from the wild-type mice were placed in phosphate buffer solution (PBS) and fragmented into small pieces. The WAT grafts were implanted in the subcutaneous tissue through small, shaved skin incisions on the dorsal region of the animal, which was anesthetized with isoflurane.…”

“…PCOS is the classic example of the loss of functional cyclicity rhythm associated with anomalous feed-back or, as it is also known as inappropriate feed-back [5]. In this case, the excessive production of androgens and their subsequent extra glandular conversion into estrogens form the pathophysiological basis for chronic anovulation [6]- [9]. Additionally, the excessive androgen production can be explained by extra-and intra-ovarian factors [10].…”