Sulfasalazine exposure during pregnancy and lactation induces alterations in reproductive behavior in adult female rat offspring. 2022

Simone Forcato, and Ana Beatriz de Oliveira Aquino, and Nathaly de Moura Camparoto, and Hannah Hamada Mendonça Lens, and Flávia Alessandra Guarnier, and Ana Carolina Inhasz Kiss, and Daniela Cristina Ceccatto Gerardin
Department of Physiological Sciences, Londrina State University, Londrina, PR, Brazil.

OBJECTIVE Sulfasalazine (SAS) is the first line drug in the treatment of chronic inflammatory bowel diseases in pregnant women. SAS and its metabolites cross the placenta and can be transferred through the milk. However, the long-term consequences to the reproductive system of offspring from dams exposed to SAS have not yet been studied. Thus, our study investigated the effects of SAS treatment during gestational and lactational periods on maternal care in F0 and reproductive outcomes in F1 females. METHODS Wistar female rats (n = 10/group) received 300 mg/kg/day of SAS dissolved in carboxymethyl cellulose (CMC), by gavage, from gestational day 0 to lactation day 21 and 3 mg/kg/day of folic acid during gestation. The control group received CMC only. On PND 21, the female pups were selected for reproductive evaluation at different time points: infancy and adulthood. The reproductive parameters evaluated were installation of puberty (vaginal opening and first estrus), estrous cyclicity, reproductive organs weight, histological analysis of the ovary follicles and uterus, analysis of oxidative stress in ovarian tissue, reproductive behavior (sexual and maternal), and fertility. RESULTS SAS treatment decreased the retrieving behavior in F0 females. The F1 females presented an increase in the lordosis score, frequency of lordosis of magnitude 3, and lipid peroxidation of ovarian tissues in both infancy and adult life. CONCLUSIONS The SAS effects observed in the current study represent a relevant concern for public health, as they demonstrated that treatment with SAS compromised the maternal motivation of dams and induced reproductive alterations in F1 females.

UI MeSH Term Description Entries
D007774 Lactation The processes of milk secretion by the maternal MAMMARY GLANDS after PARTURITION. The proliferation of the mammary glandular tissue, milk synthesis, and milk expulsion or let down are regulated by the interactions of several hormones including ESTRADIOL; PROGESTERONE; PROLACTIN; and OXYTOCIN. Lactation, Prolonged,Milk Secretion,Lactations, Prolonged,Milk Secretions,Prolonged Lactation,Prolonged Lactations
D008425 Maternal Behavior The behavior patterns associated with or characteristic of a mother. Maternal Patterns of Care,Maternal Care Patterns,Behavior, Maternal,Behaviors, Maternal,Care Pattern, Maternal,Care Patterns, Maternal,Maternal Behaviors,Maternal Care Pattern,Pattern, Maternal Care,Patterns, Maternal Care
D010053 Ovary The reproductive organ (GONADS) in female animals. In vertebrates, the ovary contains two functional parts: the OVARIAN FOLLICLE for the production of female germ cells (OOGENESIS); and the endocrine cells (GRANULOSA CELLS; THECA CELLS; and LUTEAL CELLS) for the production of ESTROGENS and PROGESTERONE. Ovaries
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011297 Prenatal Exposure Delayed Effects The consequences of exposing the FETUS in utero to certain factors, such as NUTRITION PHYSIOLOGICAL PHENOMENA; PHYSIOLOGICAL STRESS; DRUGS; RADIATION; and other physical or chemical factors. These consequences are observed later in the offspring after BIRTH. Delayed Effects, Prenatal Exposure,Late Effects, Prenatal Exposure
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000894 Anti-Inflammatory Agents, Non-Steroidal Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions. They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects. Analgesics, Anti-Inflammatory,Aspirin-Like Agent,Aspirin-Like Agents,NSAID,Non-Steroidal Anti-Inflammatory Agent,Non-Steroidal Anti-Inflammatory Agents,Nonsteroidal Anti-Inflammatory Agent,Anti Inflammatory Agents, Nonsteroidal,Antiinflammatory Agents, Non Steroidal,Antiinflammatory Agents, Nonsteroidal,NSAIDs,Nonsteroidal Anti-Inflammatory Agents,Agent, Aspirin-Like,Agent, Non-Steroidal Anti-Inflammatory,Agent, Nonsteroidal Anti-Inflammatory,Anti-Inflammatory Agent, Non-Steroidal,Anti-Inflammatory Agent, Nonsteroidal,Anti-Inflammatory Analgesics,Aspirin Like Agent,Aspirin Like Agents,Non Steroidal Anti Inflammatory Agent,Non Steroidal Anti Inflammatory Agents,Nonsteroidal Anti Inflammatory Agent,Nonsteroidal Anti Inflammatory Agents,Nonsteroidal Antiinflammatory Agents
D012460 Sulfasalazine A drug that is used in the management of inflammatory bowel diseases. Its activity is generally considered to lie in its metabolic breakdown product, 5-aminosalicylic acid (see MESALAMINE) released in the colon. (From Martindale, The Extra Pharmacopoeia, 30th ed, p907) Salicylazosulfapyridine,Asulfidine,Azulfadine,Azulfidine,Azulfidine EN,Colo-Pleon,Pleon,Pyralin EN,Salazopyrin,Salazosulfapyridine,Sulfasalazin medac,Sulfasalazin-Heyl,Sulfasalazine FNA,Sulphasalazine,Ucine,Ulcol,ratio-Sulfasalazine,Colo Pleon,Sulfasalazin Heyl,ratio Sulfasalazine
D012726 Sexual Behavior, Animal Sexual activities of animals. Mating Behavior, Animal,Sex Behavior, Animal,Animal Mating Behavior,Animal Mating Behaviors,Animal Sex Behavior,Animal Sex Behaviors,Animal Sexual Behavior,Animal Sexual Behaviors,Mating Behaviors, Animal,Sex Behaviors, Animal,Sexual Behaviors, Animal

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