¹Paulista University, Program in Environmental and Experimental Pathology, São Paulo, Brazil

Background: Lactose intolerance affects a large proportion of the population and is associated with symptoms such as diarrhea and abdominal pain; however, its underlying mechanisms remain poorly understood. Women are more frequently reported as lactose intolerant, and associations with reproductive impairments have been described. Previously, two experimental models of lactose intolerance were developed by administrating lactose-rich diets for 14 consecutive days: a 14% lactose solution and a commercial milk formula. Both diets impaired stool consistency and were validated as lactose intolerance models.

Aims & Objectives: The present study aimed to investigate whether lactose intolerance induces reproductive impairments in females, focusing on local and central mechanisms.

Method: To this end, the two lactose intolerance models (14% lactose solution and commercial formula for 14 consecutive days) were applied to adult female rats. Both lactose-rich diet groups and the control group received standard chow and water ad libitum. Morphological analyses of the uterus and ovary, including histopathology and morphometry, were performed. In addition, the expression of key genes involved in the hypothalamic-pituitary-gonadal (HPG) axis was assessed in the hypothalamus and ovary using real-time quantitative polymerase chain reaction.

Results: The results revealed epithelial hypertrophy, cellular debris, and increased myometrium thickness. Gene expression levels of gonadotropin-releasing hormone (Gnrh1), kisspeptina (Kiss1), and progesterone immunomodulatory binding factor 1 (Pibf1), as well as progesterone, luteinizing hormone (Lhcgr), and follicle-stimulating hormone (Fshr) receptors were increased.

Discussion & Conclusions: The hypothesis linking lactose intolerance to reproductive impairment was supported by observed uterine morphological alterations. The HPG axis played a key role in the interaction between lactose intolerance and reproduction, involving modulation of genes related to proteins, hormones, and receptors. Notably, the commercial formula induced more pronounced effects. In conclusion, this study provides novel insights into the diagnosis and treatment of patients with lactose intolerance, particularly with respect to reproductive comorbidities. FAPESP.