Decreased ovarian reserve and ovarian morphological alterations in female rat offspring exposed to a ketogenic maternal diet.

OBJECTIVE This study evaluates the effects of a ketogenic diet on morphology and follicle reserve. METHOD Sixteen Sprague-Dawley rats were randomized into two groups: standard diet group (n=8) and ketogenic diet group (n=8). Rats were time mated. Dams were permitted to deliver spontaneously. The animals were monitored for the onset of puberty. All the rats were weighed and anesthetized, serum anti-Müllerian hormone level was measured, and the oviducts were removed. The morphological characteristics of follicles were determined and total ovarian volumes were calculated. RESULTS The mean ovarian volume was statistically significantly lower in the ketogenic diet group compared to the standard diet group (14.41±0.99 mm3 versus 18.89±1.28 mm3) (p=0.000). The mean number of antral follicles was 13.63±1.80 in the standard diet group and 4.462±0.760 in the ketogenic diet group. The mean ovarian weight of the ketogenic diet group was significantly lower than that of the standard diet group (0.42±0.06 g versus 0.815±107 g). The mean anti-Müllerian hormone levels were significantly higher in the standard diet group compared to the ketogenic diet group (1.023±4.75 ng/mL versus 0.69±0.07 ng/mL) (p=0.000). The mean percentage of staining of Ki-67 was 35.28±4.75 in the standard diet group and 16.98±3.33 in the ketogenic diet group (p=0.000). CONCLUSION Maternal ketogenic diet reduces ovarian follicular reserve in female offspring and has important implications for maintaining reproductive potential at a population level.

[1]  E. Baracat,et al.  Nutritional and dietary aspects in polycystic ovary syndrome: insights into the biology of nutritional interventions , 2020, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[2]  L. Donini,et al.  Very-low-calorie ketogenic diet (VLCKD) in the management of metabolic diseases: systematic review and consensus statement from the Italian Society of Endocrinology (SIE) , 2019, Journal of Endocrinological Investigation.

[3]  Xueqing Wu,et al.  Maternal high-fat diet impairs follicular development of offspring through intraovarian kisspeptin/GPR54 system , 2019, Reproductive Biology and Endocrinology.

[4]  J. Krieger,et al.  Cell-free therapy with the secretome of adipose tissue-derived stem cells in rats’ frozen-thawed ovarian grafts , 2018, Stem Cell Research & Therapy.

[5]  C. Aiken,et al.  Decreased ovarian reserve, dysregulation of mitochondrial biogenesis, and increased lipid peroxidation in female mouse offspring exposed to an obesogenic maternal diet , 2015, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[6]  S. Auvin,et al.  Ketogenic diet exhibits anti‐inflammatory properties , 2015, Epilepsia.

[7]  D. Sloboda,et al.  Early-life nutritional effects on the female reproductive system. , 2015, The Journal of endocrinology.

[8]  R. García-Becerra,et al.  Maternal protein restriction during pregnancy and/or lactation negatively affects follicular ovarian development and steroidogenesis in the prepubertal rat offspring. , 2014, Archives of medical research.

[9]  P. Nathanielsz,et al.  Fetal programming of sexual development and reproductive function , 2014, Molecular and Cellular Endocrinology.

[10]  M. Wong,et al.  Effects of a ketogenic diet during pregnancy on embryonic growth in the mouse , 2013, BMC Pregnancy and Childbirth.

[11]  R. Mattar,et al.  Evaluation of FAS and caspase-3 in the endometrial tissue of patients with idiopathic infertility and recurrent pregnancy loss. , 2013, European journal of obstetrics, gynecology, and reproductive biology.

[12]  G. Cruz,et al.  Temporal window in which exposure to estradiol permanently modifies ovarian function causing polycystic ovary morphology in rats. , 2012, Fertility and sterility.

[13]  M. Meaney,et al.  Nature, nurture or nutrition? Impact of maternal nutrition on maternal care, offspring development and reproductive function , 2012, The Journal of physiology.

[14]  D. Sloboda,et al.  Maternal Undernutrition Significantly Impacts Ovarian Follicle Number and Increases Ovarian Oxidative Stress in Adult Rat Offspring , 2010, PloS one.

[15]  J. Schaffer,et al.  Diet-induced obesity model: abnormal oocytes and persistent growth abnormalities in the offspring. , 2010, Endocrinology.

[16]  P. Gluckman,et al.  Pre- and Postnatal Nutritional Histories Influence Reproductive Maturation and Ovarian Function in the Rat , 2009, PloS one.

[17]  R. Norman,et al.  Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone reverses the adverse effects of diet-induced obesity on oocyte quality. , 2008, Endocrinology.

[18]  M. Skinner.  Regulation of primordial follicle assembly and development. , 2005, Human reproduction update.

[19]  J. King.  Physiology of pregnancy and nutrient metabolism. , 2000, The American journal of clinical nutrition.

[20]  D J Barker,et al.  Fetal nutrition and adult disease. , 2000, The American journal of clinical nutrition.

[21]  P. Crumrine,et al.  The Ketogenic Diet in Refractory Epilepsy: The Experience of Children's Hospital of Pittsburgh , 2000, Clinical pediatrics.

[22]  Johannes Gerdes,et al.  Monoclonal antibodies against recombinant parts of the Ki‐67 antigen (MIB 1 and MIB 3) detect proliferating cells in microwave‐processed formalin‐fixed paraffin sections , 1992, The Journal of pathology.

[23]  J. Paavonen,et al.  Natural history of vaginal intraepithelial neoplasia , 1991, Cancer.